coumadin carboxyglutamic carboxyglutamate reijnders drittij undercarboxylated gas6 vkor phytomenadione brinkhous pivka phylloquinone menadione ronden vitamers prothrombin conotoxins menaquinone warfarin gla menatetrenone doisy suttie hydroquinone rdas carboxylation glutamyl epoxide antihemorrhagics rhéaume
where is vitamin k made in the human body
Vitamin K - wikipedia Vitamin K Jump to : navigation , search This article is about the family of vitamers . For vitamin K , the form usually used as a supplement , see Phytomenadione . <Th_colspan="2"> Vitamin K <Td_colspan="2"> Drug class <Td_colspan="2"> Vitamin K structures . MK - 4 and MK - 7 are both subtypes of K . <Th_colspan="2"> Class identifiers Use Vitamin K deficiency , Warfarin overdose ATC code B02BA Biological target Gamma - glutamyl carboxylase <Th_colspan="2"> Clinical data Drugs.com Medical Encyclopedia <Th_colspan="2"> External links MeSH D014812 <Td_colspan="2"> In Wikidata Vitamin K is a group of structurally similar , fat - soluble vitamins the human body requires for complete synthesis of certain proteins that are prerequisites for blood coagulation ( K from Koagulation , Danish for `` coagulation '' ) and which the body also needs for controlling binding of calcium in bones and other tissues . The vitamin K - related modification of the proteins allows them to bind calcium ions , which they can not do otherwise . Without vitamin K , blood coagulation is seriously impaired , and uncontrolled bleeding occurs . Preliminary clinical research indicates that deficiency of vitamin K may weaken bones , potentially leading to osteoporosis , and may promote calcification of arteries and other soft tissues . Chemically , the vitamin K family comprises 2 - methyl - 1 , 4 - naphthoquinone ( 3 - ) derivatives . Vitamin K includes two natural vitamers : vitamin K and vitamin K. Vitamin K , in turn , consists of a number of related chemical subtypes , with differing lengths of carbon side chains made of isoprenoid groups of atoms . Vitamin K , also known as phylloquinone , is made by plants , and is found in highest amounts in green leafy vegetables because it is directly involved in photosynthesis . It may be thought of as the plant form of vitamin K. It is active as a vitamin in animals and performs the classic functions of vitamin K , including its activity in the production of blood - clotting proteins . Animals may also convert it to vitamin K . Bacteria in the gut flora can also convert K into vitamin K ( menaquinone ) . In addition , bacteria typically lengthen the isoprenoid side chain of vitamin K to produce a range of vitamin K forms , most notably the MK - 7 to MK - 11 homologues of vitamin K. All forms of K other than MK - 4 can only be produced by bacteria , which use these forms in anaerobic respiration . The MK - 7 and other bacterially derived forms of vitamin K exhibit vitamin K activity in animals , but MK - 7 's extra utility over MK - 4 , if any , is unclear and is a matter of investigation . Because a synthetic form of vitamin K , vitamin K ( menadione ) , may be toxic by interfering with the function of glutathione , it is no longer used to treat vitamin K deficiency . Contents ( hide ) 1 Health effects 1.1 Osteoporosis 1.2 Cardiovascular health 1.3 Cancer 1.4 Warfarin overdose and coumadin poisoning 2 Side effects 3 Interactions 4 Chemistry 4.1 Conversion of vitamin K to vitamin K 4.2 Vitamin K 5 Physiology 6 Absorption and dietary need 7 Dietary recommendations 8 Food sources 8.1 Vitamin K 9 Deficiency 10 Biochemistry 10.1 Function in animals 10.2 Gamma - carboxyglutamate proteins 10.3 Methods of assessment 10.4 Function in bacteria 11 Injection in newborns 11.1 United States 11.2 United Kingdom 11.3 Controversy 12 History 13 References 14 Bibliography 15 External links Health effects ( edit ) Osteoporosis ( edit ) A review of 2014 concluded that there is positive evidence that monotherapy using MK - 4 , one of the forms of Vitamin K , reduces fracture incidence in post-menopausal women with osteoporosis , and suggested further research on the combined use of MK - 4 with bisphosphonates . In contrast , an earlier review article of 2013 concluded that there is no good evidence that vitamin K supplementation helps prevent osteoporosis or fractures in postmenopausal women . A Cochrane systematic review of 2006 suggested that supplementation with Vitamin K and with MK4 reduces bone loss ; in particular , a strong effect of MK - 4 on incident fractures among Japanese patients was emphasized . A review article of 2016 suggested to consider , as one of several measures for bone health , increasing the intake of foods rich in vitamins K and K . Cardiovascular Health ( edit ) Adequate intake of vitamin K is associated with the inhibition of arterial calcification and stiffening , but there have been few interventional studies and no good evidence that vitamin K supplementation is of any benefit in the primary prevention of cardiovascular disease . One 10 - year population study , the Rotterdam Study , did show a clear and significant inverse relationship between the highest intake levels of menaquinone ( mainly MK - 4 from eggs and meat , and MK - 8 and MK - 9 from cheese ) and cardiovascular disease and all - cause mortality in older men and women . Cancer ( edit ) Vitamin K has been promoted in supplement form with claims it can slow tumor growth ; there is however no good medical evidence that supports such claims . Warfarin overdose and Coumadin poisoning ( edit ) Vitamin K is one of the treatments for bleeding events caused by overdose of the anticoagulant drug warfarin ( Coumadin ® ) . Vitamin K is also part of the suggested treatment regime for poisoning by rodenticide ( coumarin poisoning ) . Side effects ( edit ) Although allergic reaction from supplementation is possible , no known toxicity is associated with high doses of the phylloquinone ( vitamin K ) or menaquinone ( vitamin K ) forms of vitamin K , so no tolerable upper intake level ( UL ) has been set . Blood clotting ( coagulation ) studies in humans using 45 mg per day of vitamin K ( as MK - 4 ) and even up to 135 mg per day ( 45 mg three times daily ) of K ( as MK - 4 ) , showed no increase in blood clot risk . Even doses in rats as high as 250 mg / kg , body weight did not alter the tendency for blood - clot formation to occur . Unlike the safe natural forms of vitamin K and vitamin K and their various isomers , a synthetic form of vitamin K , vitamin K ( menadione ) , is demonstrably toxic at high levels . The U.S. FDA has banned this form from over-the - counter sale in the United States because large doses have been shown to cause allergic reactions , hemolytic anemia , and cytotoxicity in liver cells . Interactions ( edit ) Phylloquinone ( K ) or menaquinone ( K ) are capable of reversing the anticoagulant activity of the anticoagulant warfarin ( tradename Coumadin ) . Warfarin works by blocking recycling of vitamin K , so that the body and tissues have lower levels of active vitamin K , and thus a deficiency of vitamin K . Supplemental vitamin K ( for which oral dosing is often more active than injectable dosing in human adults ) reverses the vitamin K deficiency caused by warfarin , and therefore reduces the intended anticoagulant action of warfarin and related drugs . Sometimes small amounts of vitamin K are given orally to patients taking warfarin so that the action of the drug is more predictable . The proper anticoagulant action of the drug is a function of vitamin K intake and drug dose , and due to differing absorption must be individualized for each patient . The action of warfarin and vitamin K both require two to five days after dosing to have maximum effect , and neither warfarin or vitamin K shows much effect in the first 24 hours after they are given . The newer anticoagulants dabigatran and rivaroxaban have different mechanisms of action that do not interact with vitamin K , and may be taken with supplemental vitamin K . Chemistry ( edit ) Vitamin K ( menaquinone ) . In menaquinone , the side chain is composed of a varying number of isoprenoid residues . The most common number of these residues is four , since animal enzymes normally produce menaquinone - 4 from plant phylloquinone . A sample of phytomenadione for injection , also called phylloquinone The three synthetic forms of vitamin K are vitamins K ( menadione ) , K , and K , which are used in many areas , including the pet food industry ( vitamin K ) and to inhibit fungal growth ( vitamin K ) . Conversion of vitamin K to vitamin K ( edit ) Vitamin K ( phylloquinone ) -- both forms of the vitamin contain a functional naphthoquinone ring and an aliphatic side chain . Phylloquinone has a phytyl side chain . The MK - 4 form of vitamin K is produced by conversion of vitamin K in the testes , pancreas , and arterial walls . While major questions still surround the biochemical pathway for this transformation , the conversion is not dependent on gut bacteria , as it occurs in germ - free rats and in parenterally - administered K in rats . In fact , tissues that accumulate high amounts of MK - 4 have a remarkable capacity to convert up to 90 % of the available K into MK - 4 . There is evidence that the conversion proceeds by removal of the phytyl tail of K to produce menadione as an intermediate , which is then condensed with an activated geranylgeranyl moiety ( see also prenylation ) to produce vitamin K in the MK - 4 ( menatetrenone ) form . Vitamin K ( edit ) Main article : Vitamin K Vitamin K ( menaquinone ) includes several subtypes . The two subtypes most studied are menaquinone - 4 ( menatetrenone , MK - 4 ) and menaquinone - 7 ( MK - 7 ) . Physiology ( edit ) Vitamin K , the precursor of most vitamin K in nature , is a stereoisomer of phylloquinone , an important chemical in green plants , where it functions as an electron acceptor in photosystem I during photosynthesis . For this reason , vitamin K is found in large quantities in the photosynthetic tissues of plants ( green leaves , and dark green leafy vegetables such as romaine lettuce , kale and spinach ) , but it occurs in far smaller quantities in other plant tissues ( roots , fruits , etc . ) . Iceberg lettuce contains relatively little . The function of phylloquinone in plants appears to have no resemblance to its later metabolic and biochemical function ( as `` vitamin K '' ) in animals , where it performs a completely different biochemical reaction . Vitamin K ( in animals ) is involved in the carboxylation of certain glutamate residues in proteins to form gamma - carboxyglutamate ( Gla ) residues . The modified residues are often ( but not always ) situated within specific protein domains called Gla domains . Gla residues are usually involved in binding calcium , and are essential for the biological activity of all known Gla proteins . At this time , 17 human proteins with Gla domains have been discovered , and they play key roles in the regulation of three physiological processes : Blood coagulation : prothrombin ( factor II ) , factors VII , IX , and X , and proteins C , S , and Z Bone metabolism : osteocalcin , also called bone Gla protein ( BGP ) , matrix Gla protein ( MGP ) , periostin , and the recently discovered Gla - rich protein ( GRP ) . Vascular biology : growth arrest - specific protein 6 ( Gas6 ) Unknown function : proline - rich γ - carboxyglutamyl proteins ( PRGPs ) 1 and 2 , and transmembrane γ - carboxy glutamyl proteins ( TMGs ) 3 and 4 . Like other lipid - soluble vitamins ( A , D and E ) , vitamin K is stored in the fatty tissue of the human body . Absorption and dietary need ( edit ) Previous theory held that dietary deficiency is extremely rare unless the small intestine was heavily damaged , resulting in malabsorption of the molecule . Another at - risk group for deficiency were those subject to decreased production of K by normal intestinal microbiota , as seen in broad spectrum antibiotic use . Taking broad - spectrum antibiotics can reduce vitamin K production in the gut by nearly 74 % in people compared with those not taking these antibiotics . Diets low in vitamin K also decrease the body 's vitamin K concentration . Those with chronic kidney disease are at risk for vitamin K deficiency , as well as vitamin D deficiency , and particularly those with the apoE4 genotype . Additionally , in the elderly there is a reduction in vitamin K . Dietary recommendations ( edit ) The U.S. Institute of Medicine ( IOM ) updated Estimated Average Requirements ( EARs ) and Recommended Dietary Allowances ( RDAs ) for vitamin K in 1998 . The IOM does not distinguish between K and K -- both are counted as vitamin K . At that time there was not sufficient information to establish EARs and RDAs for vitamin K . In instances such as this , the Board sets Adequate Intakes ( AIs ) , with the understanding that at some later date , AIs will be replaced by more exact information . The current AIs for adult women and men ages 19 and up are 90 and 120 μg / day , respectively . AI for pregnancy is 90 μg / day . AI for lactation is 90 μg / day . For infants up to 12 months the AI is 2 - 2.5 μg / day For children ages 1 -- 18 years the AI increases with age from 30 to 75 μg / day . As for safety , the IOM sets Tolerable upper intake levels ( known as ULs ) for vitamins and minerals when evidence is sufficient . In the case of vitamin K there is no UL , as there is not sufficient human data for adverse effects from high doses . Collectively the EARs , RDAs , AIs and ULs are referred to as Dietary Reference Intakes ( DRIs ) . The European Food Safety Authority ( EFSA ) refers to the collective set of information as Dietary Reference Values , with Population Reference Intake ( PRI ) instead of RDA , and Average Requirement instead of EAR . AI and UL defined the same as in United States . For women and men over age 18 the Adequate Intake ( AI ) is set at 70 μg / day . AI for pregnancy is 70 μg / day , for lactation 70 μg / day . For children ages 1 -- 17 years the AIs increase with age from 12 to 65 μg / day . These AIs are lower than the U.S. RDAs . The EFSA also reviewed the safety question and reached the same conclusion as in United States - that there was not sufficient evidence to set a UL for vitamin K . For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value ( % DV ) . For vitamin K labeling purposes 100 % of the Daily Value was 80 μg , but as of May 27 , 2016 it was revised upwards to 120 μg to bring it into agreement with the AI . A table of the old and new adult Daily Values is provided at Reference Daily Intake . The original deadline to be in compliance was July 28 , 2018 , but on September 29 , 2017 the FDA released a proposed rule that extended the deadline to January 1 , 2020 for large companies and January 1 , 2021 for small companies . Food sources ( edit ) See also : Vitamin K2 § Dietary sources Vitamin K ( edit ) Food Serving size Vitamin K ( μg ) Food Serving size Vitamin K ( μg ) Kale , cooked ​ ⁄ cup 531 Parsley , raw ​ ⁄ cup 246 Spinach , cooked ​ ⁄ cup , 77g 444 Spinach , raw 1 cup 145 Collards , cooked ​ ⁄ cup 418 Collards , raw 1 cup 184 Swiss chard , cooked ​ ⁄ cup 287 Swiss chard , raw 1 cup 299 Mustard greens , cooked ​ ⁄ cup 210 Mustard greens , raw 1 cup 279 Turnip greens , cooked ​ ⁄ cup 265 Turnip greens , raw 1 cup 138 Broccoli , cooked 1 cup 220 Broccoli , raw 1 cup 89 Brussels sprouts , cooked 1 cup 219 Endive , raw 1 cup 116 Cabbage , cooked ​ ⁄ cup 82 Green leaf lettuce 1 cup 71 Asparagus 4 spears 48 Romaine lettuce , raw 1 cup 57 <Td_colspan="7"> Table from `` Important information to know when you are taking : Warfarin ( Coumadin ) and Vitamin K '' , Clinical Center , National Institutes of Health Drug Nutrient Interaction Task Force . Vitamin K is found chiefly in leafy green vegetables such as spinach , swiss chard , lettuce and Brassica vegetables ( such as cabbage , kale , cauliflower , broccoli , and brussels sprouts ) and often the absorption is greater when accompanied by fats such as butter or oils . Some fruits , such as avocados , kiwifruit and grapes , also contain vitamin K. Some vegetable oils , notably soybean oil , contain vitamin K , but at levels that would require relatively large calorie consumption to meet the recommended amounts . The tight binding of vitamin K to thylakoid membranes in chloroplasts makes it less bioavailable . For example , cooked spinach has a 5 % bioavailability of phylloquinone , however , fat added to it increases bioavailability to 13 % due to the increased solubility of vitamin K in fat . Deficiency ( edit ) Main article : Vitamin K deficiency Average diets are usually not lacking in vitamin K , and primary deficiency is rare in healthy adults . Newborn infants are at an increased risk of deficiency . Other populations with an increased prevalence of vitamin K deficiency include those who suffer from liver damage or disease ( e.g. alcoholics ) , cystic fibrosis , or inflammatory bowel diseases , or have recently had abdominal surgeries . Secondary vitamin K deficiency can occur in people with bulimia , those on stringent diets , and those taking anticoagulants . Other drugs associated with vitamin K deficiency include salicylates , barbiturates , and cefamandole , although the mechanisms are still unknown . Vitamin K deficiency can result in coagulopathy , a bleeding disorder. Symptoms of K deficiency include anemia , bruising , nosebleeds and bleeding of the gums in both sexes , and heavy menstrual bleeding in women . Osteoporosis and coronary heart disease are strongly associated with lower levels of K ( menaquinone ) . Vitamin K ( as menaquinones MK - 4 through MK - 10 ) intake level is inversely related to severe aortic calcification and all - cause mortality . Biochemistry ( edit ) Function in animals ( edit ) Mechanism of action of vitamin K . The function of vitamin K in the animal cell is to add a carboxylic acid functional group to a glutamate ( Glu ) amino acid residue in a protein , to form a gamma - carboxyglutamate ( Gla ) residue . This is a somewhat uncommon posttranslational modification of the protein , which is then known as a `` Gla protein '' . The presence of two − COOH ( carboxylic acid ) groups on the same carbon in the gamma - carboxyglutamate residue allows it to chelate calcium ions . The binding of calcium ions in this way very often triggers the function or binding of Gla - protein enzymes , such as the so - called vitamin K - dependent clotting factors discussed below . Within the cell , vitamin K undergoes electron reduction to a reduced form called vitamin K hydroquinone , catalyzed by the enzyme vitamin K epoxide reductase ( VKOR ) . Another enzyme then oxidizes vitamin K hydroquinone to allow carboxylation of Glu to Gla ; this enzyme is called gamma - glutamyl carboxylase or the vitamin K - dependent carboxylase . The carboxylation reaction only proceeds if the carboxylase enzyme is able to oxidize vitamin K hydroquinone to vitamin K epoxide at the same time . The carboxylation and epoxidation reactions are said to be coupled . Vitamin K epoxide is then reconverted to vitamin K by VKOR . The reduction and subsequent reoxidation of vitamin K coupled with carboxylation of Glu is called the vitamin K cycle . Humans are rarely deficient in vitamin K because , in part , vitamin K is continuously recycled in cells . Warfarin and other 4 - hydroxycoumarins block the action of VKOR . This results in decreased concentrations of vitamin K and vitamin K hydroquinone in tissues , such that the carboxylation reaction catalyzed by the glutamyl carboxylase is inefficient . This results in the production of clotting factors with inadequate Gla . Without Gla on the amino termini of these factors , they no longer bind stably to the blood vessel endothelium and can not activate clotting to allow formation of a clot during tissue injury . As it is impossible to predict what dose of warfarin will give the desired degree of clotting suppression , warfarin treatment must be carefully monitored to avoid overdose . Gamma - carboxyglutamate proteins ( edit ) Main article : Gla domain The following human Gla - containing proteins ( `` Gla proteins '' ) have been characterized to the level of primary structure : blood coagulation factors II ( prothrombin ) , VII , IX , and X , anticoagulant proteins C and S , and the factor X-targeting protein Z . The bone Gla protein osteocalcin , the calcification - inhibiting matrix Gla protein ( MGP ) , the cell growth regulating growth arrest specific gene 6 protein ( Gas6 ) , and the four transmembrane Gla proteins ( TMGPs ) , the function of which is at present unknown . Gas6 can function as a growth factor to activate the Axl receptor tyrosine kinase and stimulate cell proliferation or prevent apoptosis in some cells . In all cases in which their function was known , the presence of the Gla residues in these proteins turned out to be essential for functional activity . Gla proteins are known to occur in a wide variety of vertebrates : mammals , birds , reptiles , and fish . The venom of a number of Australian snakes acts by activating the human blood - clotting system . In some cases , activation is accomplished by snake Gla - containing enzymes that bind to the endothelium of human blood vessels and catalyze the conversion of procoagulant clotting factors into activated ones , leading to unwanted and potentially deadly clotting . Another interesting class of invertebrate Gla - containing proteins is synthesized by the fish - hunting snail Conus geographus . These snails produce a venom containing hundreds of neuroactive peptides , or conotoxins , which is sufficiently toxic to kill an adult human . Several of the conotoxins contain two to five Gla residues . Methods of assessment ( edit ) Vitamin K status can be assessed by : The prothrombin time ( PT ) test measures the time required for blood to clot . A blood sample is mixed with citric acid and put in a fibrometer ; delayed clot formation indicates a deficiency . This test is insensitive to mild deficiency , as the values do not change until the concentration of prothrombin in the blood has declined by at least 50 % . Undercarboxylated prothrombin ( PIVKA - II ) ; in a study of 53 newborns , found `` PT ( prothrombin time ) is a less sensitive marker than PIVKA II '' , and as indicated above , PT is unable to detect subclinical deficiencies that can be detected with PIVKA - II testing . Plasma phylloquinone was found to be positively correlated with phylloquinone intake in elderly British women , but not men , but an article by Schurgers et al. reported no correlation between responses in a food frequency questionnaire and plasma phylloquinone . Urinary γ - carboxyglutamic acid responds to changes in dietary vitamin K intake . Several days are required before any change can be observed . In a study by Booth et al. , increases of phylloquinone intakes from 100 μg to between 377 and 417 μg for five days did not induce a significant change . Response may be age - specific . Undercarboxylated osteocalcin ( UcOc ) levels have been inversely correlated with stores of vitamin K and bone strength in developing rat tibiae . Another study following 78 post-menopausal Korean women found a supplement regimen of vitamins K and D , and calcium , but not a regimen of vitamin D and calcium , was inversely correlated with reduced UcOc levels . Function in bacteria ( edit ) Many bacteria , such as Escherichia coli found in the large intestine , can synthesize vitamin K ( menaquinone - 7 or MK - 7 , up to MK - 11 ) , but not vitamin K ( phylloquinone ) . In these bacteria , menaquinone transfers two electrons between two different small molecules , during oxygen - independent metabolic energy production processes ( anaerobic respiration ) . For example , a small molecule with an excess of electrons ( also called an electron donor ) such as lactate , formate , or NADH , with the help of an enzyme , passes two electrons to menaquinone . The menaquinone , with the help of another enzyme , then transfers these two electrons to a suitable oxidant , such fumarate or nitrate ( also called an electron acceptor ) . Adding two electrons to fumarate or nitrate converts the molecule to succinate or nitrite plus water , respectively . Some of these reactions generate a cellular energy source , ATP , in a manner similar to eukaryotic cell aerobic respiration , except the final electron acceptor is not molecular oxygen , but fumarate or nitrate . In aerobic respiration , the final oxidant is molecular oxygen ( O ) , which accepts four electrons from an electron donor such as NADH to be converted to water . E. coli , as facultative anaerobes , can carry out both aerobic respiration and menaquinone - mediated anaerobic respiration . Injection in newborns ( edit ) The blood clotting factors of newborn babies are roughly 30 -- 60 % that of adult values ; this may be due to the reduced synthesis of precursor proteins and the sterility of their guts . Human milk contains 1 -- 4 μg / L of vitamin K , while formula - derived milk can contain up to 100 μg / L in supplemented formulas . Vitamin K concentrations in human milk appear to be much lower than those of vitamin K. Occurrence of vitamin K deficiency bleeding in the first week of the infant 's life is estimated at 0.25 -- 1.7 % , with a prevalence of 2 -- 10 cases per 100,000 births . Premature babies have even lower levels of the vitamin , so they are at a higher risk from this deficiency . Bleeding in infants due to vitamin K deficiency can be severe , leading to hospitalization , blood transfusions , brain damage , and death . Supplementation can prevent most cases of vitamin K deficiency bleeding in the newborn . Intramuscular administration is more effective in preventing late vitamin K deficiency bleeding than oral administration . United States ( edit ) As a result of the occurrences of vitamin K deficiency bleeding , the Committee on Nutrition of the American Academy of Pediatrics has recommended 0.5 -- 1 mg of vitamin K be administered to all newborns shortly after birth . United kingdom ( edit ) In the UK vitamin K supplementation is recommended for all newborns within the first 24 hours . This is usually given as a single intramuscular injection of 1 mg shortly after birth but as a second - line option can be given by three oral doses over the first month . Controversy ( edit ) Controversy arose in the early 1990s regarding this practice , when two studies suggested a relationship between parenteral administration of vitamin K and childhood cancer , however , poor methods and small sample sizes led to the discrediting of these studies , and a review of the evidence published in 2000 by Ross and Davies found no link between the two . Doctors reported emerging concerns in 2013 , after treating children for serious bleeding problems . They cited lack of newborn vitamin K administration as the reason that the problems occurred , and recommended that breastfed babies could have an increased risk unless they receive a preventative dose . History ( edit ) In 1929 , Danish scientist Henrik Dam investigated the role of cholesterol by feeding chickens a cholesterol - depleted diet . He initially replicated experiments reported by scientists at the Ontario Agricultural College ( OAC ) . McFarlane , Graham and Richardson , working on the chick feed program at OAC , had used chloroform to remove all fat from chick chow . They noticed that chicks fed only fat - depleted chow developed hemorrhages and started bleeding from tag sites . Dam found that these defects could not be restored by adding purified cholesterol to the diet . It appeared that -- together with the cholesterol -- a second compound had been extracted from the food , and this compound was called the coagulation vitamin . The new vitamin received the letter K because the initial discoveries were reported in a German journal , in which it was designated as Koagulationsvitamin . Edward Adelbert Doisy of Saint Louis University did much of the research that led to the discovery of the structure and chemical nature of vitamin K. Dam and Doisy shared the 1943 Nobel Prize for medicine for their work on vitamin K ( K and K ) published in 1939 . Several laboratories synthesized the compound ( s ) in 1939 . For several decades , the vitamin K - deficient chick model was the only method of quantifying vitamin K in various foods : the chicks were made vitamin K - deficient and subsequently fed with known amounts of vitamin K - containing food . The extent to which blood coagulation was restored by the diet was taken as a measure for its vitamin K content . Three groups of physicians independently found this : Biochemical Institute , University of Copenhagen ( Dam and Johannes Glavind ) , University of Iowa Department of Pathology ( Emory Warner , Kenneth Brinkhous , and Harry Pratt Smith ) , and the Mayo Clinic ( Hugh Butt , Albert Snell , and Arnold Osterberg ) . The first published report of successful treatment with vitamin K of life - threatening hemorrhage in a jaundiced patient with prothrombin deficiency was made in 1938 by Smith , Warner , and Brinkhous . The precise function of vitamin K was not discovered until 1974 , when three laboratories ( Stenflo et al. , Nelsestuen et al. , and Magnusson et al . ) isolated the vitamin K - dependent coagulation factor prothrombin ( factor II ) from cows that received a high dose of a vitamin K antagonist , warfarin . It was shown that , while warfarin - treated cows had a form of prothrombin that contained 10 glutamate ( Glu ) amino acid residues near the amino terminus of this protein , the normal ( untreated ) cows contained 10 unusual residues that were chemically identified as γ - carboxyglutamate ( Gla ) . The extra carboxyl group in Gla made clear that vitamin K plays a role in a carboxylation reaction during which Glu is converted into Gla . References ( edit ) ^ Jump up to : `` Vitamin K '' . Micronutrient Information Center , Linus Pauling Institute , Oregon State University , Corvallis , OR . July 2014 . Retrieved 20 March 2017 . Jump up ^ `` Vitamin K Overview '' . University of Maryland Medical Center . Jump up ^ Hamidi , M. S. ; Gajic - Veljanoski , O. ; Cheung , A. M. ( 2013 ) . `` Vitamin K and bone health '' . Journal of Clinical Densitometry ( Review ) . 16 ( 4 ) : 409 -- 413 . doi : 10.1016 / j. jocd. 2013.08. 017 . PMID 24090644 . Jump up ^ Cockayne , S. ; Adamson , J. ; Lanham - New , S. ; Shearer , M. J. ; Gilbody , S ; Torgerson , D. J. ( Jun 2006 ) . `` Vitamin K and the prevention of fractures : systematic review and meta - analysis of randomized controlled trials '' . Archives of Internal Medicine ( Review ) . 166 ( 12 ) : 1256 -- 1261 . doi : 10.1001 / archinte. 166.12. 1256 . PMID 16801507 . Jump up ^ O'Keefe , J. H. ; Bergman , N. ; Carrera Bastos , P. ; Fontes Villalba , M. ; Di Nicolantonio , J. J. ; Cordain , L. ( 2016 ) . `` Nutritional strategies for skeletal and cardiovascular health : hard bones , soft arteries , rather than vice versa '' . Open Heart ( Review ) . 3 ( 1 ) : e000325 . doi : 10.1136 / openhrt - 2015 - 000325 . PMC 4809188 . PMID 27042317 . Jump up ^ Maresz , K. ( Feb 2015 ) . `` Proper Calcium Use : Vitamin K as a Promoter of Bone and Cardiovascular Health '' . Integrative Medicine ( Review ) . 14 ( 1 ) : 34 -- 39 . PMC 4566462 . PMID 26770129 . Jump up ^ Hartley , L. ; Clar , C. ; Ghannam , O. ; Flowers , N. ; Stranges , S. ; Rees , K. ( Sep 2015 ) . `` Vitamin K for the primary prevention of cardiovascular disease '' . The Cochrane Database of Systematic Reviews ( Systematic review ) . 9 ( 9 ) : CD011148 . doi : 10.1002 / 14651858. CD011148. pub2 . PMID 26389791 . ^ Jump up to : Geleijnse , J. M. ; Vermeer , C. ; Grobbee , D. E. ; Schurgers , L. J. ; Knapen , M. H. ; van der Meer , I. M. ; Hofman , A. ; Witteman , J. C. ( Nov 2004 ) . `` Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease : the Rotterdam Study '' . Journal of Nutrition. 134 ( 11 ) : 3100 -- 3105 . doi : 10.1093 / jn / 134.11. 3100 . PMID 15514282 . Jump up ^ Ades , T. B. , ed. ( 2009 ) . `` Vitamin K '' . American Cancer Society Complete Guide to Complementary and Alternative Cancer Therapies ( 2nd ed . ) . American Cancer Society . pp. 558 -- 563 . ISBN 978 - 0 - 944235 - 71 - 3 . Jump up ^ Ageno , W ; Gallus , AS ; Wittkowsky , A ; Crowther , M ; Hylek , EM ; Palareti , G ; American College of Chest , Physicians . ( February 2012 ) . `` Oral anticoagulant therapy : Antithrombotic Therapy and Prevention of Thrombosis , 9th ed : American College of Chest Physicians Evidence - Based Clinical Practice Guidelines '' . Chest. 141 ( 2 Suppl ) : e44S -- 88S . doi : 10.1378 / chest. 11 - 2292 . PMC 3278051 . PMID 22315269 . Jump up ^ Lung , D. ( Dec 2015 ) . Tarabar , A. , ed . `` Rodenticide Toxicity Treatment & Management '' . Medscape . WebMD . Jump up ^ Rasmussen , S. E. ; Andersen , N. L. ; Dragsted , L. O. ; Larsen , J. C. 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M. ; Hornstra , G. ; Vermeer , C. ( Jul 1997 ) . `` Modulation of arterial thrombosis tendency in rats by vitamin K and its side chains '' . Atherosclerosis. 132 ( 1 ) : 61 -- 67 . doi : 10.1016 / S0021 - 9150 ( 97 ) 00087 - 7 . PMID 9247360 . Jump up ^ Ansell , J. ; Hirsh , J. ; Poller , L. ; Bussey , H. ; Jacobson , A. ; Hylek , E ( Sep 2004 ) . `` The pharmacology and management of the vitamin K antagonists : the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy '' . Chest. 126 ( 3 Suppl . ) : 204S -- 233S . doi : 10.1378 / chest. 126.3 _suppl. 204S . PMID 15383473 . Jump up ^ Crowther , M. A. ; Douketis , J. D. ; Schnurr , T. ; Steidl , L. ; Mera , V. ; Ultori , C. ; Venco , A. ; Ageno , W. ( Aug 2002 ) . `` Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin - associated coagulopathy . A randomized , controlled trial '' . 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Jump up ^ Dituri , F. ; Buonocore , G. ; Pietravalle , A. ; Naddeo , F. ; Cortesi , M ; Pasqualetti , P ; Tataranno M. L. ; R. , Agostino ( Sep 2012 ) . `` PIVKA - II plasma levels as markers of subclinical vitamin K deficiency in term infants '' . Journal of Maternal , Fetal & Neonatal Medicine . 25 ( 9 ) : 1660 -- 1663 . doi : 10.3109 / 14767058.2012. 657273 . PMID 22280352 . Jump up ^ Thane , C. W. ; Bates , C. J. ; Shearer , M. J. ; Unadkat , N ; Harrington , D. J. ; Paul , A . A. ; Prentice , A. ; Bolton - Smith , C. ( Jun 2002 ) . `` Plasma phylloquinone ( vitamin K ) concentration and its relationship to intake in a national sample of British elderly people '' . British Journal of Nutrition. 87 ( 6 ) : 615 -- 622 . doi : 10.1079 / BJNBJN2002582 . PMID 12067432 . Jump up ^ McKeown , N. M. ; Jacques , P. F. ; Gundberg , C. M. ; Peterson , J. W. ; Tucker , K. L. ; Kiel , D. P. ; Wilson , P. 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Proceedings of the Society of Experimental Biology and Medicine . 37 ( 4 ) : 628 -- 630 . doi : 10.3181 / 00379727 - 37 - 9668P . Jump up ^ Stenflo , J ; Fernlund , P. ; Egan , W. ; Roepstorff , P. ( Jul 1974 ) . `` Vitamin K dependent modifications of glutamic acid residues in prothrombin '' . Proceedings of the National Academy of Sciences of the United States of America . 71 ( 7 ) : 2730 -- 2733 . doi : 10.1073 / pnas. 71.7. 2730 . PMC 388542 . PMID 4528109 . Jump up ^ Nelsestuen , G. L. ; Zytkovicz , T. H. ; Howard , J. B. ( Oct 1974 ) . `` The mode of action of vitamin K. Identification of gamma - carboxyglutamic acid as a component of prothrombin '' ( PDF ) . Journal of Biological Chemistry . 249 ( 19 ) : 6347 -- 6350 . PMID 4214105 . Jump up ^ Magnusson , S. ; Sottrup - Jensen , L. ; Petersen , T. E. ; Morris , H. R. ; Dell , A. ( Aug 1974 ) . `` Primary structure of the vitamin K - dependent part of prothrombin '' . 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External links ( edit ) `` Vitamin K : Another Reason to Eat Your Greens '' . <Th_colspan="2"> Vitamins ( A11 ) Fat soluble α - Carotene β - Carotene Retinol Tretinoin Ergosterol Ergocalciferol 7 - Dehydrocholesterol Previtamin D Cholecalciferol 25 - hydroxycholecalciferol Calcitriol ( 1 , 25 - dihydroxycholecalciferol ) Calcitroic acid Dihydroergocalciferol D analogues Alfacalcidol Dihydrotachysterol Calcipotriol Tacalcitol Paricalcitol Tocopherol Alpha Beta Gamma Delta Tocotrienol Alpha Beta Gamma Delta Tocofersolan Naphthoquinone Phylloquinone ( K ) Menaquinones ( K ) Menadione ( K ) ‡ Menadiol ( K ) Water soluble Thiamine B analogues Acefurtiamine Allithiamine Fursultiamine Octotiamine Prosultiamine Sulbutiamine Riboflavin Niacin Nicotinamide Pantothenic acid Dexpanthenol Pantethine Pyridoxine , Pyridoxal phosphate Pyridoxamine Pyritinol Biotin Folic acid Dihydrofolic acid Folinic acid Levomefolic acid Adenosylcobalamin Cyanocobalamin Hydroxocobalamin Methylcobalamin Choline Ascorbic acid Dehydroascorbic acid Combinations Multivitamins <Td_colspan="2"> WHO - EM Withdrawn from market Clinical trials : Phase III Never to phase III <Th_colspan="2"> Enzyme cofactors Active forms vitamins TPP / ThDP ( B ) FMN , FAD ( B ) NAD , NADH , NADP , NADPH ( B ) Coenzyme A ( B ) PLP / P5P ( B ) Biotin ( B ) THFA / H FA , DHFA / H FA , MTHF ( B ) AdoCbl , MeCbl ( B ) Ascorbic acid ( C ) Phylloquinone ( K ) , Menaquinone ( K ) Coenzyme F420 non-vitamins ATP CTP SAMe PAPS GSH Coenzyme B Cofactor F430 Coenzyme M Coenzyme Q Heme / Haem ( A , B , C , O ) Lipoic Acid Methanofuran Molybdopterin / Molybdenum cofactor PQQ THB / BH THMPT / H MPT metal ions Ca Cu Fe , Fe Mg Mn Mo Ni Zn Base forms vitamins : see vitamins <Th_colspan="2"> Antihemorrhagics ( B02 ) Antihemorrhagics ( coagulation ) Systemic Vitamin K Phytomenadione ( K ) Menadione ( K ) Coagulation factors intrinsic : IX / Nonacog alfa VIII / Moroctocog alfa / Turoctocog alfa extrinsic : VII / Eptacog alfa common : X II / Thrombin I / Fibrinogen XIII / Catridecacog combinations : Prothrombin complex concentrate ( II , VII , IX , X , protein C and S ) Other systemic Etamsylate Carbazochrome Batroxobin thrombopoietin receptor agonist ( Romiplostim Eltrombopag ) Local Absorbable gelatin sponge Oxidized cellulose Tetragalacturonic acid hydroxymethylester Thrombin Collagen Calcium alginate Epinephrine / Adrenalone Antifibrinolytics amino acids ( Aminocaproic acid Tranexamic acid Aminomethylbenzoic acid ) serpins ( Aprotinin Alfa1 antitrypsin C1 - inhibitor Camostat ) NDL : 00576745 Retrieved from `` https://en.wikipedia.org/w/index.php?title=Vitamin_K&oldid=827530757 '' Categories : Vitamin K Vitamins Antihemorrhagics 1 , 4 - Naphthoquinones Terpenes and terpenoids Vitamers Hidden categories : Use dmy dates from September 2013 Template : drugs.com link with non-standard subpage All articles with unsourced statements Articles with unsourced statements from May 2013 Articles containing potentially dated statements from 2007 All articles containing potentially dated statements Talk Contents About Wikipedia Afrikaans Azərbaycanca Bân - lâm - gú Български Bosanski Català Čeština Dansk Deutsch ދިވެހިބަސް Eesti Español Euskara فارسی Français Galego 한국어 हिन्दी Hrvatski Bahasa Indonesia Íslenska Italiano עברית Basa Jawa ქართული Кыргызча Latviešu Lietuvių മലയാളം Bahasa Melayu မြန်မာဘာသာ Nederlands नेपाली 日本 語 Norsk Norsk nynorsk Occitan Polski Português Română Русский Scots Simple English Slovenščina Српски / srpski Srpskohrvatski / српскохрватски Basa Sunda Suomi Svenska தமிழ் ไทย Türkçe Тыва дыл Українська Tiếng Việt 中文 Edit links This page was last edited on 25 February 2018 , at 07 : 17 . 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