Vitamin k1

If you are taking the over-the-counter product to self-treat, read all directions on the product package before taking this medication. If you have any questions, consult your pharmacist. If your doctor has prescribed this medication, take it as directed. If you are using the rapidly-dissolving tablets, place under your tongue to dissolve, then swallow with or without water. Some brands may also be swallowed whole. The dosage is based on your age, medical condition and response to treatment.

Do not increase your dose or use this drug more often or for longer than directed. Your condition will not improve any faster, and your risk of side effects will increase. If you are using a certain " blood thinner" drug ( warfarin), vitamin K can decrease the effects of warfarin for up to 2 weeks. Be sure to take your vitamin K and warfarin exactly as directed by your doctor or pharmacist. If you develop easy bruising or bleeding, or if you think you may have a serious medical problem, get medical help right away.

You may need another dose of vitamin K. Vitamin K usually vitamin k1 no side effects. If you have any unusual effects, contact your doctor or pharmacist promptly. If your doctor has directed you to use this product, remember that your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this product do not have serious side effects.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice vitamin k1 symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/ tongue/throat), severe dizziness, trouble breathing. This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. In the US - Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. Before taking vitamin K, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: blood disorders, gallbladder disease (such as obstructive jaundice, biliary fistula), liver disease. Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). During pregnancy, this product should be used only when clearly needed.

Discuss the risks and benefits with your doctor. Vitamin K passes into breast milk, but is unlikely to harm a nursing infant. Consult your doctor before breast-feeding. Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions.

Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist.

Do not start, stop, or change the dosage of any medicines without your doctor's approval. Some products that may interact with this drug include: " blood thinners" (such as acenocoumarol, warfarin).

Avoid taking this medication at the same time as orlistat (a weight-management drug). Wait at least 2 hours between taking this medication and orlistat because taking them together may decrease the effect of vitamin K.

Lab tests (such as prothrombin time, INR) may be done while you are taking this product. Keep all medical and lab appointments. Consult your doctor for more details. Remember that it is best to get your vitamins and minerals from food whenever possible.

Eat a well- balanced diet, and follow any dietary guidelines as directed by your doctor. Foods rich in vitamin K include green leafy vegetables such as spinach, collards, and broccoli.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult vitamin k1 pharmacist or local waste disposal company. Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, except as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of vitamin k1 professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else.

A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment. Health Solutions • Penis Curved When Erect? • Could I have CAD? • Treat Bent Fingers • Treat HR+, HER2- MBC • Tired of Dandruff? • Benefits of CBD • Rethink MS Treatment • AFib-Related Strokes • Risk of a Future DVT/PE • Is My Penis Normal?

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Severe reactions, including fatalities, have also been reported following INTRAMUSCULAR administration. Typically these severe reactions have resembled hypersensitivity or anaphylaxis, including shock and cardiac and/or vitamin k1 arrest. Some patients have exhibited these severe reactions on receiving phytonadione for the first time.

Therefore the INTRAVENOUS and INTRAMUSCULAR routes should be restricted to those situations where the subcutaneous route is not feasible and the serious risk involved is considered justified. Description Phytonadione is a vitamin, which is a clear, yellow to amber, viscous, odorless or nearly odorless liquid. It is insoluble in water, soluble in chloroform and slightly soluble in ethanol.

It has a molecular weight of 450.70. Phytonadione is 2-methyl-3-phytyl-1, 4-naphthoquinone. Its empirical formula is C31H46O2 and its structural formula is: Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) is a yellow, sterile, nonpyrogenic aqueous dispersion available for injection by the intravenous, intramuscular and subcutaneous routes. Each milliliter contains phytonadione 2 or 10 mg, vitamin k1 fatty acid derivative 70 mg, dextrose, hydrous 37.5 mg in water for injection; benzyl alcohol 9 mg added as preservative.

May contain hydrochloric acid for pH adjustment. pH is 6.3 (5.0 to 7.0). Phytonadione is oxygen sensitive. Clinical Pharmacology Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) aqueous dispersion of Vitamin K1 for parenteral injection, possesses the same type and degree of activity as does naturally-occurring vitamin K, which is necessary for the production via the liver of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X).

The prothrombin test is sensitive to the levels of three of these four factors-II, VII, and X. Vitamin K is an essential cofactor for a microsomal enzyme that catalyzes the post-translational carboxylation of multiple, specific, peptide-bound glutamic acid residues in inactive hepatic precursors of factors II, VII, IX, and X. The resulting gamma-carboxy-glutamic acid residues convert the precursors into active coagulation factors that are subsequently secreted by liver cells into the blood.

Phytonadione is readily absorbed following intramuscular administration. After absorption, phytonadione is initially concentrated in the liver, but the concentration declines rapidly. Very little vitamin K accumulates in tissues. Little is known about the metabolic fate of vitamin K.

Almost no free unmetabolized vitamin K appears in bile or urine. In normal animals and humans, phytonadione is virtually devoid of pharmacodynamic activity. However, in animals and humans deficient in vitamin K, the pharmacological action of vitamin K is related to its normal physiological function, that is, to promote the hepatic biosynthesis of vitamin K dependent clotting factors.

The action of the aqueous dispersion, when administered intravenously, is generally detectable within an hour or two and hemorrhage is usually controlled within 3 to 6 hours. A normal prothrombin level may often be obtained in 12 to 14 hours. In the prophylaxis and treatment of hemorrhagic disease of the newborn, phytonadione has demonstrated a greater margin of safety than that of the water-soluble vitamin K analogues.

Indications and Usage Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) is indicated in the following coagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity. Vitamin K1 Injection is indicated in: • anticoagulant-induced prothrombin vitamin k1 caused by coumarin or indanedione derivatives; • prophylaxis and therapy of hemorrhagic disease of the newborn; • hypoprothrombinemia due to antibacterial therapy; • hypoprothrombinemia secondary to factors limiting absorption or synthesis of vitamin K, e.g., obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal vitamin k1, cystic fibrosis of the pancreas, and regional enteritis; • other drug-induced hypoprothrombinemia where it is definitely shown that the result is due to interference with vitamin K metabolism, e.g., salicylates.

Contraindications Hypersensitivity to any component of this medication. Warnings Benzyl alcohol as a preservative in Bacteriostatic Sodium Chloride Injection has been associated with toxicity in newborns.

Data are unavailable on the toxicity of other preservatives in this age group. There is no evidence to suggest that the vitamin k1 amount of benzyl alcohol contained in Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP), when used vitamin k1 recommended, is associated with toxicity. An immediate coagulant effect should not be expected after administration of phytonadione.

It takes a minimum of 1 to 2 hours for measurable improvement in the prothrombin time. Whole blood or component therapy may also be necessary if bleeding is severe. Phytonadione will not counteract the anticoagulant action of heparin. When Vitamin K1 is used to correct excessive anticoagulant-induced hypoprothrombinemia, anticoagulant therapy still being indicated, the patient is again faced with the clotting hazards existing prior to starting the anticoagulant therapy.

Phytonadione is not a clotting agent, but overzealous therapy with Vitamin K1 may restore conditions which originally permitted thromboembolic phenomena.

Dosage should be kept as low as possible, and prothrombin time should be checked regularly as clinical conditions indicate. Repeated large doses of vitamin K are not warranted in liver disease if the response to initial use of the vitamin is unsatisfactory. Failure to respond to vitamin K may indicate that the condition being treated is inherently unresponsive to vitamin K. Benzyl alcohol has been reported to be associated with a fatal “Gasping Syndrome” in premature infants.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired.

Premature neonates are particularly at risk because their kidneys are immature, and they required large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity.

Tissue loading may occur at even lower rates of administration. Precautions Drug Interactions Temporary resistance to prothrombin-depressing anticoagulants may result, especially when larger doses of phytonadione are used. If relatively large doses have been employed, it may be necessary when reinstituting vitamin k1 therapy to use somewhat larger doses of the prothrombin- depressing anticoagulant, or to use one which acts on a different principle, such as heparin sodium.

Laboratory Tests Prothrombin time should be checked regularly as clinical conditions indicate. Carcinogenesis, Mutagenesis, Impairment of Fertility Studies of carcinogenicity, mutagenesis or impairment of fertility have not been conducted with Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP).

Pregnancy Pregnancy Category C: Animal reproduction studies have not been conducted with Vitamin K1 Injection. It is also not known whether Vitamin K1 Injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Vitamin K1 Injection should be given to a pregnant woman only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Vitamin K1 Injection is administered to a nursing woman.

Pediatric Use Hemolysis, jaundice, and hyperbilirubinemia in neonates, particularly those that are premature, may be related to the dose of Vitamin K1 Injection. Therefore, the recommended dose should not be exceeded (see ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION). Adverse Reactions Deaths have occurred after intravenous and intramuscular administration. (See Box Warning.) Transient “flushing sensations” and “peculiar” sensations of taste have been observed, vitamin k1 well as rare instances of dizziness, rapid and weak pulse, profuse sweating, brief hypotension, dyspnea, and cyanosis.

Pain, swelling, and tenderness at the injection site may occur. The possibility of allergic sensitivity including an anaphylactoid reaction, should be kept in mind. Infrequently, usually after repeated injection, erythematous, indurated, pruritic plaques have occurred; rarely, these have progressed vitamin k1 scleroderma-like lesions that have persisted for long periods.

In other cases, these lesions have resembled erythema perstans. Hyperbilirubinemia has been observed in the newborn following administration of phytonadione. This has occurred rarely and primarily with doses above those recommended. (See PRECAUTIONS, Pediatric Use.) Overdosage The intravenous LD50 of Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) in the mouse is vitamin k1 and 52 vitamin k1 for the 0.2% and 1% concentrations, respectively.

Dosage and Administration Whenever possible, Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) should be given by the subcutaneous route. (See Box Warning.) When intravenous administration is considered unavoidable, the drug vitamin k1 be injected very slowly, not exceeding 1 mg per minute. Protect from light at all times. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Directions for Dilution Vitamin K1 Injection may be diluted vitamin k1 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or 5% Dextrose and Sodium Chloride Injection.

Benzyl alcohol as a preservative has been associated with toxicity in newborns. Therefore,all of the above diluents should be preservative-free (see WARNINGS). Other diluents should not be used. When dilutions are indicated, vitamin k1 should be started immediately after mixture with the diluent, vitamin k1 unused portions of the dilution should be discarded, as well as unused contents of the ampul. Prophylaxis of Hemorrhagic Disease of the Vitamin k1 The American Academy of Pediatrics recommends that Vitamin K1 be given to the newborn.

A single intramuscular dose of Vitamin K1 Injection 0.5 to 1 mg within one hour of birth is recommended. Treatment of Hemorrhagic Disease of the Newborn Empiric administration of Vitamin K1 should not replace proper laboratory evaluation of the coagulation mechanism. A prompt response (shortening of the prothrombin time in 2 to 4 hours) following administration of Vitamin K1 is usually diagnostic of hemorrhagic disease of the newborn, and failure to respond indicates another diagnosis or coagulation disorder.

Vitamin K1 Injection 1 mg should be given either subcutaneously or intramuscularly. Higher doses may be necessary if the mother has been receiving oral anticoagulants. Whole blood or component therapy may be indicated if bleeding is excessive.

This therapy, however, does not correct the underlying disorder and Vitamin K1 Injection should be given concurrently. Anticoagulant-Induced Prothrombin Deficiency in Adults To correct excessively prolonged prothrombin time caused by oral anticoagulant therapy—2.5 to 10 mg or up to 25 mg initially is recommended. In rare instances 50 mg may be required. Frequency and amount of subsequent doses should be determined by prothrombin time response or clinical condition (see WARNINGS).

If in 6 to 8 hours after parenteral administration the prothrombin time has not been shortened satisfactorily, the dose should be repeated. In the event of shock or excessive blood loss, the use of whole blood or vitamin k1 therapy is indicated. Hypoprothrombinemia Due to Other Causes in Adults A dosage of 2.5 to 25 mg or more (rarely up to 50 mg) is recommended, the amount and route of administration depending upon the severity of the condition and response obtained. If possible, discontinuation or reduction of the dosage of drugs interfering with coagulation mechanisms (such as salicylates; antibiotics) is suggested as an alternative to administering concurrent Vitamin K1 Injection.

The severity of the coagulation disorder should determine whether the immediate administration of Vitamin K1 Injection is required in addition to discontinuation or reduction of interfering drugs.

How Supplied Vitamin K1 Injection vitamin k1 Injectable Emulsion, USP) is supplied in a package of 25 as follows: Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from light. Keep ampuls in tray until time of use. ©Hospira 2004 EN-0538 Printed in USA HOSPIRA, INC., LAKE FOREST, IL 60045 USA Sample Outer Label More about Vitamin K1 (phytonadione) • Side effects • Drug interactions • Dosage information • During pregnancy or Breastfeeding • Reviews (1) • Compare alternatives • Pricing & coupons • En español • Drug class: anticoagulant reversal agents Professional resources • Prescribing Information • Phytonadione Tablets (FDA) Other brands Mephyton, Aquamephyton Related treatment guides • Hypoprothrombinemia, Anticoagulant Induced • Vitamin K Deficiency • Hypoprothrombinemia, Not Associated with Anticoagulant Therapy • Hypoprothrombinemia, Prophylaxis Medical Disclaimer Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products.

This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Data sources include IBM Watson Micromedex (updated 3 May 2022), Cerner Multum™ (updated 28 Apr 2022), ASHP (updated 11 Apr 2022) and others.
Vitamin K is a group of vitamins found in some green vegetables. Vitamins K1 ( phytonadione) and K2 (menaquinone) are commonly available as supplements. Vitamin K is an essential vitamin k1 needed by the body for blood clotting, bone building, and other important processes.

It's found in leafy green vegetables, broccoli, and Brussels sprouts. The name vitamin K comes from the German word "Koagulationsvitamin." People commonly use vitamin K for blood clotting problems or for reversing the blood thinning effects of warfarin.

It is also used for osteoporosis, athletic performance, breast cancer, diabetes, and many other conditions, but there is no good scientific evidence to support most of these other uses.

• Bleeding problems in newborns with low levels of vitamin K (hemorrhagic disease). Giving newborns vitamin K1 by mouth or as a shot into the muscle helps prevent bleeding.

Shots seem to work the best, but can only be given by a healthcare provider. • Low levels of the blood clotting protein prothrombin (hypoprothrombinemia). Taking vitamin K1 by mouth or by IV can prevent and treat bleeding problems in people with low levels of prothrombin.

IV products can only be given by a healthcare provider. • A rare, inherited bleeding disorder (vitamin K-dependent clotting factors deficiency or VKCFD). Taking vitamin K by mouth or by IV can help prevent bleeding in people with VKCFD. IV products can only be given by a healthcare provider. • Reversing the blood thinning effects of warfarin.

Taking vitamin K1 by mouth or by IV can reverse the effects of warfarin, a blood thinner. IV products can only be given by a healthcare provider. • Bleeding into or around the fluid-filled areas (ventricles) of the brain (intraventricular hemorrhage).

Taking vitamin K by mouth vitamin k1 pregnant doesn't seem to prevent bleeding in the brain of preterm infants. It also doesn't seem to reduce the risk of nerve injury caused by these bleeds. There is interest in using vitamin K for a number of other purposes, but there isn't enough reliable information to say whether it might be helpful.

When taken by mouth: The two forms of vitamin K (vitamin K1 and vitamin K2) are likely safe when taken appropriately.

Vitamin K1 10 mg daily and vitamin K2 45 mg daily have been safely used for up to 2 years. It's usually well-tolerated, but some people may have an upset stomach or diarrhea. When applied to the skin: Vitamin K1 is possibly safe for most people when applied as a cream that contains 0.1% vitamin K1. Pregnancy and breast-feeding: Vitamin K is likely safe when taken in recommended amounts of 90 mcg daily for those over 19 years old.

Don't use higher amounts without the advice of a healthcare professional. Children: Vitamin K1 is likely safe when taken by mouth appropriately. Kidney disease: Too much vitamin K can be harmful if you vitamin k1 receiving dialysis treatments vitamin k1 to kidney disease.

Liver disease: Vitamin K is not effective for treating clotting problems caused by severe liver disease. In fact, high doses of vitamin K can make clotting problems worse in these people. Reduced bile secretion: People with decreased bile secretion might not absorb vitamin K supplements very well. Vitamin k1 with this condition might need to take supplemental bile salts along with vitamin K to improve absorption.

Major Interaction Do not take this combination• Warfarin (Coumadin) interacts with VITAMIN K Vitamin K is used by the body to help the blood clot. Warfarin is used to slow blood clotting. By helping the blood clot, vitamin K might decrease the effects of warfarin. Be sure to have your blood checked regularly. The dose of your warfarin might need to be changed. Vitamin K is an essential vitamin. It is found in leafy green vegetables, broccoli, and Brussels sprouts.

It's recommended that males over 19 years old consume 120 vitamin k1 daily, and females over 19 years old consume 90 mcg daily. While pregnant and breast-feeding, 90 mcg should be consumed daily. Recommended amounts for children depend on age. Speak with a healthcare provider to find out what dose might be best for a specific condition.

Ageno, W., Crowther, M., Steidl, L., Ultori, C., Mera, V., Dentali, F., Squizzato, A., Marchesi, C., and Venco, A. Low dose oral vitamin K to reverse acenocoumarol-induced coagulopathy: a randomized controlled trial.

Thromb.Haemost. 2002;88(1):48-51. View abstract. Ageno, W., Garcia, D., Silingardi, M., Galli, M., and Crowther, M. A randomized trial comparing 1 mg of oral vitamin K with no treatment in the management of warfarin-associated coagulopathy in patients with mechanical heart valves.

J.Am.Coll.Cardiol. 8-16-2005;46(4):732-733. View abstract. Andersen, P. and Godal, H. C. Predictable reduction in anticoagulant activity of warfarin by small amounts of vitamin K.

Acta Med.Scand. 1975;198(4):269-270. View abstract. Bakhshi, S., Deorari, A. K., Roy, S., Paul, V. K., and Singh, M. Prevention of subclinical vitamin K deficiency based on PIVKA-II levels: oral versus intramuscular route. Indian Pediatr. 1996;33(12):1040-1043.

View abstract. Beker, L. T., Ahrens, R. A., Fink, R. J., O'Brien, M. E., Davidson, Vitamin k1. W., Sokoll, L. J., and Sadowski, J. A. Effect of vitamin K1 supplementation on vitamin K status in cystic fibrosis patients. J.Pediatr.Gastroenterol.Nutr. 1997;24(5):512-517. View abstract. Bolton-Smith, C., McMurdo, M. E., Paterson, C.

R., Mole, P. A., Harvey, J. M., Fenton, S. T., Prynne, C. J., Mishra, G. D., and Shearer, M. J. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women.

J.Bone Miner.Res. 2007;22(4):509-519. View abstract. Booth, S. L., Broe, K. E., Gagnon, D. R., Tucker, K. L., Hannan, M. T., McLean, R. R., Dawson-Hughes, B., Wilson, P. W., Cupples, L.

A., and Kiel, D. P. Vitamin K intake and bone mineral density in women and men. Am.J.Clin.Nutr. 2003;77(2):512-516.

View abstract. Booth, S. L., O'Brien-Morse, M. E., Dallal, G. E., Davidson, K. W., and Gundberg, C. M. Response of vitamin K status to different intakes and sources of phylloquinone-rich foods: comparison of younger and older adults.

Am.J.Clin.Nutr. 1999;70(3):368-377. View abstract. Boulis, N. M., Bobek, M. P., Schmaier, A., and Hoff, J. T. Use of factor IX complex in warfarin-related intracranial hemorrhage.

Neurosurgery 1999;45(5):1113-1118. View abstract. Braam, L. A., Knapen, M. H., Geusens, P., Brouns, F., and Vermeer, C. Factors affecting bone loss in female endurance athletes: a two-year follow-up study. Am.J.Sports Med. 2003;31(6):889-895. View abstract. Braam, L. A., Knapen, M. H., Geusens, P., Brouns, F., Hamulyak, K., Gerichhausen, M. J., and Vermeer, C. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age.

Calcif.Tissue Int. 2003;73(1):21-26. View abstract. Brophy, M. T., Fiore, L. D., and Deykin, D. Low-Dose Vitamin K Therapy in Excessively Anticoagulated Patients: A Dose-Finding Study.

J.Thromb.Thrombolysis. 1997;4(2):289-292. View abstract. Brousson, M. A. and Klein, M. C. Controversies surrounding the administration of vitamin K to newborns: a review. CMAJ. 2-1-1996;154(3):307-315. View abstract. Byrd, D. C., Stephens, M. A., Hamann, G. L., and Dorko, C. Subcutaneous phytonadione for reversal of warfarin-induced elevation of the International Normalized Ratio. Am.J.Health Syst.Pharm. vitamin k1. View abstract. Cartmill, M., Dolan, G., Byrne, J. L., and Byrne, P. O. Prothrombin complex concentrate for oral anticoagulant reversal in neurosurgical emergencies.

Br.J.Neurosurg. 2000;14(5):458-461. View abstract. Cheung, A. M., Tile, L., Lee, Y., Tomlinson, G., Hawker, G., Scher, J., Vitamin k1, H., Vieth, R., Thompson, L., Jamal, S., and Josse, R. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS.Med. 10-14-2008;5(10):e196. View abstract. Chow, C. K. Dietary intake of menaquinones and risk of cancer incidence and mortality.

Am.J.Clin.Nutr. 2010;92(6):1533-1534. View abstract. Cornelissen, E. A., Kollee, L. A., De Abreu, R. A., Motohara, K., and Monnens, L. A. Prevention of vitamin K deficiency in infancy vitamin k1 weekly administration of vitamin K. Acta Paediatr. 1993;82(8):656-659. View abstract. Cornelissen, E. A., Kollee, L. A., De Abreu, R. A., van Baal, J. M., Motohara, K., Verbruggen, B., and Monnens, L.

A. Effects of oral and intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting factors in breast fed infants. Arch.Dis.Child 1992;67(10):1250-1254. View abstract. Cornelissen, E. A., Kollee, L. A., van Lith, T. G., Motohara, K., and Monnens, L. A.

Evaluation of a daily dose of 25 micrograms vitamin K1 to prevent vitamin K deficiency in breast-fed infants. J.Pediatr.Gastroenterol.Nutr. 1993;16(3):301-305. View abstract. Crosier, M. D., Peter, I., Booth, S. L., Bennett, G., Dawson-Hughes, B., and Ordovas, J. M. Association of sequence variations in vitamin K epoxide reductase and gamma-glutamyl carboxylase genes with biochemical measures of vitamin K status.

J.Nutr.Sci.Vitaminol.(Tokyo) 2009;55(2):112-119. View abstract. Crowther, C. A., Crosby, D. D., and Henderson-Smart, D. J. Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane.Database.Syst.Rev. 2010;(1):CD000229. View abstract. Crowther, M. A., Donovan, D., Harrison, L., McGinnis, J., and Ginsberg, J. Low-dose oral vitamin K reliably reverses over-anticoagulation due to warfarin.

Thromb.Haemost. 1998;79(6):1116-1118. View abstract. Crowther, M. A., Douketis, J. D., Schnurr, T., Steidl, L., Mera, V., Ultori, C., Venco, A., and Ageno, W.

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. Ann.Intern.Med. 8-20-2002;137(4):251-254. View abstract. Crowther, M. A., Julian, J., McCarty, D., Douketis, J., Kovacs, M., Biagoni, L., Schnurr, Vitamin k1, McGinnis, J., Gent, M., Hirsh, J., and Ginsberg, J. Treatment of warfarin-associated coagulopathy with oral vitamin K: a randomised controlled trial.

Lancet 11-4-2000;356(9241):1551-1553. View abstract. Dennis VC, Ripley TL, Planas LG, and Beach P. Dietary vitamin K in oral anticoagulation patients: clinician practices and knowledge in outpatient settings. J Pharm Technol 2008;24(2):69-76. Dentali, F. and Ageno, W. Management of coumarin-associated coagulopathy in the non-bleeding patient: a systematic review. Haematologica 2004;89(7):857-862.

View abstract. Dentali, F., Ageno, W., and Crowther, M. Treatment of coumarin-associated coagulopathy: a systematic review and proposed treatment algorithms. J.Thromb.Haemost. 2006;4(9):1853-1863. View abstract. Deveras, R. A. and Kessler, C. M. Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa concentrate. Ann.Intern.Med. 12-3-2002;137(11):884-888. View abstract. Dezee, K. J., Shimeall, W. T., Douglas, K. M., Shumway, N.

M., and O'malley, P. G. Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. Arch.Intern.Med. 2-27-2006;166(4):391-397. View abstract. Dickson, R. C., Stubbs, T. M., and Lazarchick, J. Antenatal vitamin K therapy of the low-birth-weight infant. Am.J.Obstet.Gynecol. 1994;170(1 Pt 1):85-89. View abstract. Dougherty, K. A., Schall, J.

I., and Stallings, V. A. Suboptimal vitamin K status despite supplementation in children and young adults with cystic fibrosis.

Am.J.Clin.Nutr. 2010;92(3):660-667. View abstract. Drury, D., Grey, V. L., Ferland, G., Gundberg, C., and Lands, L. C. Efficacy of high dose phylloquinone in correcting vitamin K deficiency in cystic fibrosis. J.Cyst.Fibros. 2008;7(5):457-459. View abstract. Duong, T. M., Plowman, B. K., Morreale, A.

P., and Janetzky, K. Retrospective and prospective analyses of the treatment of overanticoagulated patients. Pharmacotherapy 1998;18(6):1264-1270. View abstract. Eisai Co.Ltd. Eisai announces vitamin k1 intermediate analysis of anti-osteoporosis treatment post-marketing research to investigate the benefits of menatetrenone as part of the Ministry of Health, Labour and Welfare's Pharmacoepidemiological Drug Review Program. 2005; Evans, G., Luddington, R., and Baglin, T. Beriplex P/N reverses severe warfarin-induced overanticoagulation immediately and completely in patients presenting with major bleeding.

Br.J.Haematol. 2001;115(4):998-1001. View abstract. Fetrow, C. W., Overlock, T., and Leff, L. Antagonism of warfarin-induced hypoprothrombinemia with use of low-dose subcutaneous vitamin K1. J.Clin.Pharmacol. 1997;37(8):751-757. View abstract.

Fondevila, C. G., Grosso, S. H., Santarelli, M. T., and Pinto, M. D. Reversal of excessive oral anticoagulation with a low oral dose of vitamin K1 compared with acenocoumarine discontinuation. A prospective, randomized, open study. Blood Coagul.Fibrinolysis 2001;12(1):9-16. View abstract. Gijsbers, B. L., Jie, K. S., and Vermeer, C. Effect of food composition on vitamin K absorption in human volunteers.

Br.J.Nutr. 1996;76(2):223-229. View abstract. Glover, Vitamin k1. J. and Morrill, G. B. Conservative treatment of vitamin k1 patients. Chest 1995;108(4):987-990. View abstract. Goldstein, J. N., Thomas, S. H., Frontiero, V., Vitamin k1, A., Engel, C., Snider, R., Smith, E. E., Greenberg, S.

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A., Shearer, M. J., Pace, D. G., and Joubert, P. H. A new mixed micellar preparation for oral vitamin K prophylaxis: randomised controlled comparison with an intramuscular formulation in breast fed infants.

Arch.Dis.Child 1998;79(4):300-305. View abstract. Habu, D., Shiomi, S., Tamori, A., Takeda, T., Tanaka, T., Kubo, S., and Nishiguchi, S. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver.

JAMA 7-21-2004;292(3):358-361. View abstract. Hathaway, W. E., Isarangkura, P. B., Mahasandana, C., Jacobson, L., Pintadit, P., Pung-Amritt, P., and Green, G. M. Comparison of oral and parenteral vitamin K prophylaxis for prevention of late hemorrhagic disease of the newborn. J.Pediatr. 1991;119(3):461-464. View abstract. Hogenbirk, K., Peters, M., Bouman, P., Sturk, A., and Buller, H. A. The effect of formula versus breast feeding and exogenous vitamin K1 supplementation on circulating levels of vitamin K1 and vitamin K-dependent clotting factors in newborns.

Eur.J.Pediatr. 1993;152(1):72-74. View abstract. Hosoi, T. [Treatment of primary osteoporosis with vitamin K2]. Clin.Calcium 2007;17(11):1727-1730. View abstract. Hotta, N., Ayada, M., Sato, K., Ishikawa, T., Okumura, A., Matsumoto, E., Ohashi, T., and Kakumu, S. Effect of vitamin K2 on the recurrence in patients with hepatocellular carcinoma.

Hepatogastroenterology 2007;54(79):2073-2077. View abstract. Hung, A., Singh, S., and Tait, R. C. A prospective randomized study to determine the optimal dose of intravenous vitamin K in reversal of over-warfarinization. Br.J.Haematol. 2000;109(3):537-539. View abstract. Hylek, E. M., Chang, Y. C., Skates, S. J., Hughes, Vitamin k1. A., and Singer, D. E. Prospective study of the outcomes of ambulatory patients with excessive warfarin anticoagulation. Arch.Intern.Med. 6-12-2000;160(11):1612-1617.

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J.Bone Miner.Metab 2009;27(1):66-75. View abstract. Ishida, Y. [Vitamin K2]. Clin.Calcium 2008;18(10):1476-1482. View abstract. Ishida, Y. and Kawai, S. Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study.

Am.J.Med. 10-15-2004;117(8):549-555. View abstract. Iwamoto, J. [Anti-fracture efficacy of vitamin K]. Clin.Calcium 2009;19(12):1805-1814. View abstract. Iwamoto, J., Matsumoto, H., and Takeda, T. Efficacy of menatetrenone (vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases: meta-analysis of three randomized, controlled trials.

Clin.Drug Investig. 2009;29(7):471-479. [RETRACTED]. View abstract. Iwamoto, J., Sato, Y., Takeda, T., and Matsumoto, H. High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Nutr.Res. 2009;29(4):221-228. View abstract.

Iwamoto, J., Takeda, T., and Ichimura, S. Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. J.Orthop.Sci. 2000;5(6):546-551. View abstract. Iwamoto, J., Takeda, T., and Ichimura, S. Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate. J.Orthop.Sci. 2001;6(6):487-492. View abstract.

Iwamoto, J., Takeda, T., and Sato, Y. Role of vitamin K2 in the treatment of postmenopausal osteoporosis. Curr.Drug Saf 2006;1(1):87-97. View abstract. Jie, K. S., Bots, M. L., Vermeer, C., Witteman, J. C., and Grobbee, D. E. Vitamin K intake and osteocalcin levels in women with and without aortic atherosclerosis: a population-based study. Atherosclerosis 1995;116(1):117-123. View abstract.

Jones, K. S., Bluck, L. J., Wang, L. Y., and Coward, W. A. A stable isotope method for the simultaneous measurement of vitamin K1 (phylloquinone) kinetics and absorption. Eur.J.Clin.Nutr. 2008;62(11):1273-1281. View abstract. Jorgensen, F. S., Felding, P., Vinther, S., and Andersen, G. E. Vitamin K to neonates. Peroral versus intramuscular administration. Acta Paediatr.Scand. 1991;80(3):304-307. View abstract. Kalkwarf, H. J., Khoury, J. C., Bean, J., and Elliot, J.

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M., Poland, R. L., Grietsell, L. A., Fujii, Y., and Brans, Y. W. Maternal administration of vitamin K does not improve the coagulation profile of preterm infants. Pediatrics 1989;84(6):1045-1050. View abstract. Kim, H. S., Park, J. W., Jang, J. S., Kim, H. J., Shin, W. G., Kim, K. H., Lee, J. H., Kim, H. Y., and Jang, M. K. Prognostic values of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in hepatitis B virus-related hepatocellular carcinoma: a prospective study.

J.Clin.Gastroenterol. 2009;43(5):482-488. View abstract. Klebanoff, M. A., Read, J. S., Mills, J. L., and Shiono, P. H. The risk of childhood cancer after neonatal exposure to vitamin K.

N.Engl.J.Med. 9-23-1993;329(13):905-908. View abstract. Knapen, M. H., Schurgers, L. J., and Vermeer, C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women.

Osteoporos.Int. 2007;18(7):963-972. View abstract. Kumar, D., Greer, F. R., Super, D. M., Suttie, J. W., and Moore, J. J. Vitamin K status of premature infants: implications for current recommendations. Pediatrics 2001;108(5):1117-1122. View abstract. Liu, J., Wang, Q., Gao, F., He, J. W., and Zhao, J. H. Maternal antenatal administration of vitamin K1 results in increasing the activities of vitamin K-dependent coagulation factors in umbilical blood and in decreasing the incidence rate of vitamin k1 hemorrhage in premature infants.

J.Perinat.Med. 2006;34(2):173-176. View abstract. Liu, J., Wang, Vitamin k1, Zhao, J. H., Chen, Vitamin k1. H., and Qin, G. L. The combined antenatal corticosteroids and vitamin K therapy for preventing periventricular-intraventricular hemorrhage in premature newborns less than 35 weeks gestation.

J.Trop.Pediatr. 2006;52(5):355-359. View abstract. Lousberg, T. R., Witt, D. M., Beall, D. G., Carter, B. L., and Malone, D. C. Evaluation of excessive anticoagulation in a group model health maintenance organization. Arch.Intern.Med. 3-9-1998;158(5):528-534. View abstract. Lubetsky, A., Hoffman, R., Zimlichman, R., Eldor, A., Zvi, J., Kostenko, V., and Brenner, B. Efficacy and safety of a prothrombin complex concentrate (Octaplex) for rapid reversal of oral anticoagulation.

Thromb.Res. 2004;113(6):371-378. View abstract. Lubetsky, A., Yonath, H., Olchovsky, D., Loebstein, R., Halkin, H., and Ezra, D. Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. Arch.Intern.Med. 11-10-2003;163(20):2469-2473. View abstract. Maas, A.

H., van der Schouw, Y. T., Beijerinck, D., Deurenberg, J. J., Mali, W. P., Grobbee, D. E., and van der Graaf, Vitamin k1. Vitamin K intake and calcifications in breast arteries.

Maturitas 3-20-2007;56(3):273-279. View abstract. Macdonald, H. M., McGuigan, F. E., Lanham-New, S. A., Fraser, W. D., Ralston, S. H., and Reid, D. M. Vitamin K1 intake is associated with higher bone mineral density and reduced bone resorption in early postmenopausal Scottish women: no evidence of gene-nutrient interaction with apolipoprotein E polymorphisms.

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Thromb.Haemost. 1997;77(3):477-480. View abstract. Malik, S., Udani, R. H., Bichile, S. K., Agrawal, R. M., Bahrainwala, A. T., and Tilaye, S. Comparative study of oral versus injectable vitamin K in neonates. Indian Pediatr. 1992;29(7):857-859. View abstract. Marti-Carvajal, A. J., Cortes-Jofre, M., and Marti-Pena, A. J. Vitamin K for upper gastrointestinal bleeding in patients with liver diseases. Cochrane.Database.Syst.Rev. 2008;(3):CD004792. View abstract.

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Arch.Pediatr. 1995;2(4):328-332. View abstract. Morales, W. J., Angel, J. L., O'Brien, W. F., Knuppel, R. A., and Marsalisi, F. The use of antenatal vitamin K in the prevention of early neonatal intraventricular hemorrhage. Am.J.Obstet.Gynecol. 1988;159(3):774-779. View abstract. Motohara, K., Endo, F., and Matsuda, I. Effect of vitamin K administration on acarboxy prothrombin (PIVKA-II) levels in newborns.

Lancet 8-3-1985;2(8449):242-244. View abstract. Motohara, K., Endo, F., and Matsuda, I. Vitamin K deficiency in breast-fed infants at one month of age.

J.Pediatr.Gastroenterol.Nutr. 1986;5(6):931-933. View abstract. Napolitano, M., Mariani, G., and Lapecorella, M. Hereditary combined deficiency of the vitamin K-dependent clotting factors. Orphanet.J.Rare.Dis. 2010;5:21. View abstract. Nee, R., Doppenschmidt, D., Donovan, D. J., and Andrews, T. C. Intravenous versus subcutaneous vitamin K1 in reversing excessive oral anticoagulation. Am.J.Cardiol. 1-15-1999;83(2):286-287. View abstract. Nimptsch, K., Rohrmann, S., and Linseisen, J.

Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am.J.Clin.Nutr. 2008;87(4):985-992. View abstract. Nimptsch, Vitamin k1, Rohrmann, S., Kaaks, R., and Linseisen, J. Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg).

Am.J.Clin.Nutr. 2010;91(5):1348-1358. View abstract. Nishiguchi, S., Shimoi, S., Vitamin k1, H., Tamori, A., Habu, D., Takeda, T., and Kubo, S. Randomized pilot trial of vitamin K2 for bone loss in patients with primary biliary cirrhosis. J.Hepatol. 2001;35(4):543-545. View abstract. Novotny, J. A., Kurilich, A. C., Britz, S. J., Baer, D. J., and Clevidence, B. A. Vitamin K absorption and kinetics in human subjects after consumption of 13C-labelled phylloquinone from kale.

Br.J.Nutr. 2010;104(6):858-862. View abstract. O'Connor, M. E. and Addiego, J. E., Jr. Use of oral vitamin K1 to prevent hemorrhagic disease of the newborn infant. J.Pediatr. 1986;108(4):616-619. View abstract. Olson, R. E., Chao, J., Graham, D., Bates, M. W., and Lewis, J. H. Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake.

Br.J.Nutr. 2002;87(6):543-553. View abstract. Patel, R. J., Witt, D. M., Saseen, J. J., Tillman, D. J., and Wilkinson, D. S. Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation. Pharmacotherapy 2000;20(10):1159-1166. View abstract. Pathak A, Hamm CR, Eyal FG, Walter K, Rijhsinghani A, and Bohlman M.

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Blood Coagul.Fibrinolysis 1993;4(5):739-741. View abstract. Penning-van Beest, F. Vitamin k1, Rosendaal, F. R., Grobbee, D. E., van, Meegen E., and Stricker, B. H. Course of the international Normalized Ratio in response to oral vitamin K1 in patients overanticoagulated with phenprocoumon. Br.J.Haematol. 1999;104(2):241-245. View abstract. Poli, D., Antonucci, E., Lombardi, A., Gensini, G. F., Abbate, R., and Prisco, D. Safety and effectiveness of low dose oral vitamin K1 administration in asymptomatic out-patients on warfarin or acenocoumarol with excessive anticoagulation.

Haematologica 2003;88(2):237-238. View abstract. Pomerance, J. J., Teal, J. G., Gogolok, J. F., Brown, S., and Stewart, M. E. Maternally administered antenatal vitamin K1: effect on neonatal prothrombin activity, partial thromboplastin time, and intraventricular hemorrhage. Obstet.Gynecol. 1987;70(2):235-241. View abstract. Preston, F. E., Laidlaw, S. T., Sampson, B., and Kitchen, S. Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients.

Br.J.Haematol. 2002;116(3):619-624. View abstract. Vitamin k1 prevents first gastrointestinal bleeding in non-ascitic cirrhotic patients. Final report of a multicenter randomized trial. The Italian Multicenter Project for Propranolol in Prevention of Bleeding.

J.Hepatol. 1989;9(1):75-83. View abstract. Puckett, R. M. and Offringa, M. Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane.Database.Syst.Rev. 2000;(4):CD002776. View abstract. Raj, G., Kumar, R., and McKinney, W. P. Time course of reversal of anticoagulant effect of warfarin by intravenous and subcutaneous phytonadione.

Arch.Intern.Med. 12-13-1999;159(22):2721-2724. View abstract. Rashid, M., Durie, P., Andrew, M., Kalnins, D., Shin, J., Corey, M., Tullis, E., and Pencharz, P. B. Prevalence of vitamin K deficiency in cystic fibrosis. Am.J.Clin.Nutr. 1999;70(3):378-382. View abstract. Rees, K., Guraewal, S., Wong, Y. L., Majanbu, D. L., Mavrodaris, A., Stranges, S., Kandala, N. B., Clarke, A., and Franco, O. H. Is vitamin K consumption associated with cardio-metabolic disorders?

A systematic review. Maturitas 2010;67(2):121-128. View abstract. Riegert-Johnson, D. Vitamin k1. and Volcheck, G. W. The incidence of anaphylaxis following intravenous phytonadione (vitamin K1): a 5-year retrospective review. Ann.Allergy Asthma Immunol. 2002;89(4):400-406.

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Sasaki, N., Kusano, E., Takahashi, H., Ando, Y., Yano, K., Tsuda, E., and Asano, Y. Vitamin K2 inhibits glucocorticoid-induced bone loss partly by preventing the reduction of osteoprotegerin (OPG). J.Bone Miner.Metab 2005;23(1):41-47. View abstract. Sato, Y., Honda, Y., Hayashida, N., Iwamoto, J., Kanoko, T., and Satoh, K. Vitamin K deficiency and osteopenia in elderly women with Alzheimer's disease. Arch.Phys.Med.Rehabil. 2005;86(3):576-581. [RETRACTED]. View abstract.

Sato, Y., Honda, Y., Kaji, M., Asoh, T., Hosokawa, K., Kondo, I., and Satoh, K. Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency. Bone 2002;31(1):114-118. [RETRACTED].

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Bone 1998;23(3):291-296. [RETRACTED]. View abstract. Sato, Y., Kaji, M., Tsuru, T., Satoh, K., and Kondo, I. Vitamin K deficiency and osteopenia in vitamin D-deficient elderly women with Parkinson's disease.

Arch.Phys.Med.Rehabil. 2002;83(1):86-91. [RETRACTED]. View abstract. Sato, Y., Kanoko, T., Satoh, K., and Iwamoto, J. Vitamin k1 and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease. Bone 2005;36(1):61-68. [RETRACTED]. View abstract. Sato, Y., Tsuru, T., Oizumi, K., and Kaji, M. Vitamin K deficiency and osteopenia in disuse-affected limbs of vitamin D-deficient elderly stroke patients.

Am.J.Phys.Med.Rehabil. 1999;78(4):317-322. [RETRACTED]. View abstract. Sharma, R. K., Marwaha, N., Kumar, P., and Vitamin k1, A. Effect of oral water soluble vitamin K on PIVKA-II levels in newborns. Indian Pediatr. 1995;32(8):863-867. View abstract. Shea, M. K., Booth, S. L., Gundberg, C. M., Peterson, J. W., Waddell, C., Dawson-Hughes, B., and Saltzman, E. Adulthood obesity is positively associated with adipose tissue concentrations of vitamin K and inversely associated with circulating indicators of vitamin K status in men and women.

J.Nutr. 2010;140(5):1029-1034. View abstract. Shea, M. K., O'Donnell, C. J., Hoffmann, U., Dallal, G. E., Dawson-Hughes, B., Ordovas, J. M., Price, P. A., Williamson, M. K., and Booth, S. L. Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am.J.Clin.Nutr. 2009;89(6):1799-1807. View abstract. Shetty, H. G., Backhouse, G., Bentley, D. P., and Routledge, P. A. Effective reversal vitamin k1 warfarin-induced excessive anticoagulation with low dose vitamin K1.

Thromb.Haemost. 1-23-1992;67(1):13-15. View abstract. Vitamin k1 M. Vitamin K2 effects on the risk of fractures and on lumbar bone mineral density in osteoporosis - a randomized prospective open-label 3-year study. Osteoporos Vitamin k1 2002;13:S160. Somekawa, Y., Chigughi, M., Harada, M., and Ishibashi, T. Use of vitamin K2 (menatetrenone) and 1,25-dihydroxyvitamin D3 in the prevention of bone loss induced by leuprolide. J.Clin.Endocrinol.Metab 1999;84(8):2700-2704.

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Blood Coagul.Fibrinolysis 2003;14(5):469-477. View abstract. Stevenson, M., Lloyd-Jones, M., and Papaioannou, D. Vitamin K to prevent fractures in older women: systematic review and economic evaluation. Health Technol.Assess. 2009;13(45):iii-134. View abstract.

Summaries for patients. Is vitamin K helpful for people who have taken too much warfarin? Ann.Intern.Med. 3-3-2009;150(5):I25. View abstract. Sutherland, J. M., Glueck, H. I., and Gleser, G. Hemorrhagic disease of the newborn. Breast feeding as a necessary factor in the pathogenesis. Am.J.Dis.Child 1967;113(5):524-533. View abstract. Tabb, M. M., Sun, A., Zhou, C., Grun, F., Errandi, J., Romero, K., Pham, H., Inoue, S., Mallick, S., Lin, M., Forman, B. M., and Blumberg, B.

Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol.Chem. 11-7-2003;278(45):43919-43927. View abstract. Taberner, D. A., Thomson, J. M., vitamin k1 Poller, L. Comparison of prothrombin complex concentrate and vitamin K1 in oral anticoagulant reversal. Br.Med.J. 7-10-1976;2(6027):83-85. View abstract. Thijssen, H. H. and Drittij-Reijnders, M. J. Vitamin K status in human tissues: tissue-specific accumulation of phylloquinone and menaquinone-4.

Br.J.Nutr. 1996;75(1):121-127. View abstract. Thijssen, H. H., Vervoort, L. M., Schurgers, L. J., and Shearer, M. J. Menadione is a metabolite of oral vitamin K. Br.J.Nutr. 2006;95(2):260-266. View abstract. Thorp, J. A., Parriott, J., Ferrette-Smith, D., Meyer, B. A., Cohen, G. R., and Johnson, J. Antepartum vitamin K and phenobarbital for preventing intraventricular hemorrhage in the premature newborn: a randomized, double-blind, placebo-controlled trial.

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Villines, T. C., Hatzigeorgiou, C., Feuerstein, I. M., O'malley, P. G., and Taylor, A. J. Vitamin K1 intake and coronary calcification. Coron.Artery Dis. 2005;16(3):199-203. View abstract. Watson, Vitamin k1. G., Baglin, T., Laidlaw, S. L., Makris, M., and Preston, F. E. A comparison of the efficacy and rate of response to oral and intravenous Vitamin K in reversal of over-anticoagulation with warfarin. Br.J.Haematol.

2001;115(1):145-149. View abstract. Weibert, R. T., Le, D. T., Kayser, S. R., and Rapaport, S. I. Correction of excessive anticoagulation with low-dose oral vitamin K1. Ann.Intern.Med. 6-15-1997;126(12):959-962. View abstract. Wentzien, T. H., O'Reilly, R. A., and Kearns, P. J. Prospective evaluation of anticoagulant reversal with oral vitamin K1 while continuing vitamin k1 therapy unchanged.

Chest 1998;114(6):1546-1550. View abstract. White, R. H., McKittrick, T., Takakuwa, J., Callahan, C., McDonell, M., and Fihn, S. Management and prognosis of life-threatening bleeding during warfarin therapy. National Consortium of Anticoagulation Clinics. Arch.Intern.Med. 6-10-1996;156(11):1197-1201. View abstract. Wilson, D. C., Rashid, M., Durie, P.

R., Tsang, A., Kalnins, D., Andrew, M., Corey, M., Shin, J., Tullis, E., and Pencharz, P. B. Treatment of vitamin K deficiency in cystic fibrosis: Effectiveness of a daily fat-soluble vitamin combination. J.Pediatr. 2001;138(6):851-855. View abstract. Yamauchi, M., Yamaguchi, T., Nawata, K., Takaoka, S., and Sugimoto, T. Relationships between undercarboxylated osteocalcin and vitamin K intakes, bone turnover, and bone mineral density in healthy women.

Clin.Nutr. 2010;29(6):761-765. View abstract. Yang, Y. M., Simon, N., Maertens, P., Brigham, S., and Liu, P. Maternal-fetal transport of vitamin K1 and its effects on coagulation in premature infants. J.Pediatr. 1989;115(6):1009-1013. View abstract. Yasaka, M., Sakata, T., Minematsu, K., and Naritomi, H.

Correction of INR by prothrombin complex concentrate and vitamin K in patients with warfarin related hemorrhagic complication.

Thromb.Res. 10-1-2002;108(1):25-30. View abstract. Yasaka, M., Sakata, T., Naritomi, H., and Minematsu, K. Optimal dose of prothrombin complex concentrate for acute reversal of oral anticoagulation. Thromb.Res. 2005;115(6):455-459. View abstract. Yoshiji, H., Noguchi, R., Toyohara, M., Ikenaka, Y., Kitade, M., Kaji, K., Yamazaki, M., Yamao, J., Mitoro, A., Sawai, M., Yoshida, M., Fujimoto, M., Tsujimoto, T., Kawaratani, H., Uemura, M., and Fukui, H.

Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. J.Hepatol. 2009;51(2):315-321. View abstract. Iwamoto I, Kosha S, Noguchi S, et al. A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy. Maturitas 1999;31:161-4. View abstract. Abdel-Rahman MS, Alkady EA, Ahmed S.

Menaquinone-7 as a novel pharmacological therapy in the treatment of rheumatoid arthritis: A clinical study. Eur J Pharmacol. 2015;761:273-8. View abstract. Al-Terkait F, Charalambous H. Severe coagulopathy secondary to vitamin K deficiency in patient with small-bowel resection and rectal cancer.

Lancet Oncol 2006;7:188. View abstract. Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Chest 2008;133:160S-98S. View abstract. Becker GL. The case against mineral oil. Am J Digestive Dis 1952;19:344-8. View abstract. Bendich A, Langseth Vitamin k1. Safety of vitamin A. Am J Clin Nutr 1989;49:358-71.

View abstract. Beulens JW, Bots ML, Atsma F, et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis 2009;203:489-93. View abstract. Bhat RV, Deshmukh CT. A study of Vitamin K status in children on prolonged antibiotic therapy.

Indian Pediatr 2003;40:36-40. View abstract. Bitensky L, Hart JP, Catterall A, et al. Circulating vitamin K levels in patients with fractures. J Bone Joint Surg Br 1988;70:663-4. View abstract. Bleyer WA, Skinner AL. Fatal neonatal hemorrhage after maternal anticonvulsant therapy. JAMA 1976;235:626-7. Bolton-Smith C, Price RJ, Fenton ST, et al. Compilation of a provisional UK database for the phylloquinone (vitamin K1) content of foods. Br J Nutr 2000;83:389-99. View abstract.

Bolzetta F, Veronese N, Stubbs B, et al. The relationship between dietary vitamin K and depressive symptoms in late adulthood: A cross-sectional analysis from a large cohort study. Nutrients. 2019;11(4). pii: E787. View abstract. Booth SL, Dallal G, Shea MK, et al.

Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab 2008;93:1217-23. View abstract. Booth SL, Golly I, Sacheck JM, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr. 2004;80(1):143-8. View abstract. Booth SL, Tucker KL, Chen H, et al. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women.

Am J Clin Nutr 2000;71:1201-8. View abstract. Caluwé R, Vandecasteele S, Van Vlem B, Vermeer C, De Vriese AS.

Vitamin k1 K2 supplementation in haemodialysis patients: a randomized dose-finding study. Nephrol Dial Transplant. 2014;29(7):1385-90. View abstract. Camacho-Barcia ML, Bulló M, Garcia-Gavilán JF, et al. Association of dietary vitamin K1 intake with the incidence of cataract surgery in an adult Mediterranean population: a secondary analysis of a randomized clinical trial.

JAMA Ophthalmol. 2017;135(6):657-61. View abstract. Caraballo PJ, Heit JA, Atkinson EJ, et al. Long-term use of oral anticoagulants and the risk of fracture. Arch Intern Med 1999;159:1750-6. View abstract. Chen HG, Sheng LT, Zhang YB, et al. Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis.

Eur J Nutr 2019;58(6):2191-205. doi: 10.1007/s00394-019-01998-3. View abstract. Cockayne S, Adamson J, Lanham-New S, et al. Vitamin K and the prevention of fractures. systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 2006;166:1256-61.

View abstract. Conly JM, Stein K, Worobetz L, Rutledge-Harding S. The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K.

Am J Gastroenterol 1994;89:915-23. View abstract. Cornelissen M, Steegers-Theunissen R, Kollee L, et al. Supplementation of vitamin K in pregnant women receiving anticonvulsant therapy prevents neonatal vitamin K deficiency.

Am J Vitamin k1 Gynecol 1993;168:884-8. View abstract. Cornelissen M, Steegers-Theunissen R, Kollee L, et al. Increased incidence of neonatal vitamin K deficiency resulting from maternal anticonvulsant therapy. Am J Obstet Gynecol 1993;168:923-8.

View abstract. Corrigan JJ Jr, Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA 1974;230:1300-1. View abstract. Crowther MA, Ageno W, Garcia D, et al.

Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med.

2009;150(5):293-300. View abstract. Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA 1999;281:235-42. View abstract. Davies VA, Rothberg AD, Argent AC, Atkinson PM, Staub H, Pienaar NL.

Precursor prothrombin status in patients receiving anticonvulsant drugs. Lancet 1985;1:126-8. View abstract. Dietary vitamin K guidance: an effective strategy for stable control of oral anticoagulation? Nutr Rev. 2010;68(3):178-81. View abstract. Douglas AS, Robins SP, Hutchison JD, et al. Carboxylation of osteocalcin in post-menopausal osteoporotic women following vitamin K and D supplementation. Bone 1995;17:15-20. View abstract. Dowd P, Zheng ZB. On the mechanism of the anticlotting action of vitamin E quinone.

Proc Natl Acad Sci U S A 1995;92:8171-5. View abstract. Duggan P, O'Brien M, Kiely M, et al. Vitamin K status in patients with Crohn's disease and relationship to bone turnover. Am J Gastroenterol 2004;99:2178-85.

View abstract. Feskanich D, Weber P, Willett WC, et al. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 1999;69:74-9. View abstract. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc.

Washington, DC: National Academy Press, 2002. Available at: www.nap.edu/books/0309072794/html/. Ganbat D, Jugder BE, Ganbat L, et al. The efficacy of Vitamin K, a member of Naphthoquinones in the treatment of cancer: a systematic review and meta-analysis.

Curr Cancer Drug Targets. 2021. View abstract. Geleijnse JM, Vermeer C, Grobbee DE, et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: The Rotterdam Study. J Nutr vitamin k1. View abstract. Goldin BR, Lichtenstein AH, Gorbach SL. Nutritional and metabolic roles of intestinal flora. In: Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease, 8th ed. Malvern, PA: Lea & Febiger, 1994.

Hardman JG, Limbird LL, Molinoff PB, eds. Goodman and Gillman's The Pharmacological Basis of Therapeutics, 9th ed. New York, NY: McGraw-Hill, 1996. Hart JP, Shearer MJ, Klenerman L, et al. Electrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis. J Clin Endocrinol Metab 1985;60:1268-9. View abstract. Hashimoto H, Iwasa S, Yanai-Takahashi T, et al. Randomized, Double-Blind, Placebo-Controlled Phase ?

Study on the Efficacy and Safety of Vitamin K1 Ointment for Cetuximab or Panitumumab-Induced Acneiform Eruptions-VIKTORIA Study. Gan To Kagaku Ryoho. 2020;47(6):933-939. View abstract. Haubenstock A, Schmidt P, Zazgornik J, Balcke P, Vitamin k1 H. Hypoprothrombobinaemic bleeding associated with ceftriaxone. Lancet 1983;1:1215-6. View abstract. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin.

Am J Health Syst Pharm 2000;57:1221-7. View abstract. Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6:S43-5. View abstract. Hodges SJ, Akesson K, Vergnaud P, et al. Circulating levels of vitamins K1 and K2 decreased in elderly women with hip fracture.

J Bone Miner Res 1993;8:1241-5. View abstract. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

Chest 2012;141:e152S-e184S. View abstract. Hooper CA, Haney BB, Stone HH. Gastrointestinal bleeding due to vitamin K deficiency in patients on parenteral cefamandole. Lancet 1980;1:39-40. View abstract. Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized vitamin k1 trials. Osteoporos Int. 2015;26(3):1175-86. View abstract. Jagannath VA, Fedorowicz Z, Thaker V, Chang AB.

Vitamin K supplementation for cystic fibrosis. Cochrane Database Syst Rev. 2011;(1):CD008482. View abstract. Vitamin k1 VA, Thaker V, Chang AB, Price AI. Vitamin K supplementation for cystic fibrosis. Cochrane Database Syst Rev. 2020;6(6):CD008482. View abstract. Jamal Vitamin k1, Browner WS, Bauer DC, Cummings SR. Warfarin use and risk for osteoporosis in elderly women. Vitamin k1 of Osteoporotic Fractures Research Group.

Ann Intern Med 1998;128:829-832. View abstract. Jie KG, Bots ML, Vermeer C, et al. Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study. Calcif Tissue Int 1996;59:352-6. View abstract.

Juanola-Falgarona M, Salas-Salvadó J, Martínez-González MÁ, Corella D, Estruch R, Ros E, Fitó M, Arós F, Gómez-Gracia E, Fiol M, Lapetra J, Basora J, Lamuela-Raventós RM, Serra-Majem L, Pintó X, Muñoz MÁ, Ruiz-Gutiérrez V, Fernández-Ballart J, Bulló M. Dietary intake of vitamin K is inversely associated with mortality risk. J Nutr. 2014;144(5):743-50. View abstract. Kanai T, Takagi T, Masuhiro K, et al. Serum vitamin K level and bone mineral density in post-menopausal women. Int J Gynaecol Obstet 1997;56:25-30.

View abstract. Keith DA, Gundberg CM, Japour A, et al. Vitamin K-dependent proteins and anticonvulsant medication. Clin Pharmacol Ther 1983;34:529-32. View abstract. Kim JS, Nafziger AN, Gaedigk A, et al. Vitamin k1 of oral vitamin K on S- and R-warfarin pharmacokinetics and vitamin k1 enhanced safety of warfarin as a CYP2C9 probe. J Clin Pharmacol. 2001 Jul;41(7):715-22. View abstract. Knapen MH, Hamulyak K, Vermeer C. The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary calcium excretion.

Ann Intern Med 1989;111:1001-5. View abstract. Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32. View abstract. Kobayashi K, Haruta T, Maeda H, et al.

Cerebral hemorrhage associated with vitamin K deficiency in congenital tuberculosis treated with isoniazid and rifampin. Pediatr Infect Dis J 2002;21:1088-90. View abstract. Kuang X, Liu C, Guo X, Li K, Deng Q, Li D.

The vitamin k1 effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food Funct. 2020;11(4):3280-3297. View abstract. Kurnik D, Lobestein R, Rabinovitz H, et al. Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients.

Thromb Haemost vitamin k1. View abstract. Lanzillo R, Moccia M, Carotenuto A, Vacchiano V, Satelliti B, Panetta V, Brescia Morra V. Vitamin K cream reduces reactions at the injection site in patients with relapsing-remitting multiple sclerosis treated with subcutaneous interferon beta - VIKING study. Mult Scler. 2015;21(9):1215-6. View abstract. Löwensteyn YN, Jansen NJG, van Heerde M, et al. Increasing the dose of oral vitamin k1 K prophylaxis and its effect on bleeding risk.

Eur J Pediatr 2019;178(7):1033-42. doi: 10.1007/s00431-019-03391-y. View abstract. MacWalter RS, Fraser HW, Armstrong KM. Orlistat enhances warfarin effect. Ann Pharmacother 2003;37:510-2. View abstract. Martin-Lopez, J. E., Carlos-Gil, A. M., Rodriguez-Lopez, R., Villegas-Portero, R., Luque-Romero, L., and Flores-Moreno, S. [Prophylactic vitamin K for vitamin K deficiency bleeding of the newborn.]. Farm.Hosp. 2011;35(3):148-55. View abstract. Matsunaga S, Ito H, Sakou T.

The effect of vitamin K and D supplementation on ovariectomy-induced bone loss. Vitamin k1 Tissue Int 1999;65:285-9. View abstract. McDuffie JR, Calis KA, Booth SL, et al. Effects of orlistat on fat-soluble vitamins in obese adolescents. Pharmacotherapy 2002;22:814-22. View abstract. McFarlin BK, Henning AL, Venable AS.

Oral consumption of vitamin K2 for 8 weeks associated with increased maximal cardiac output during exercise. Altern Ther Health Med. 2017;23(4):26-32. View abstract. Miesner AR, Sullivan TS. Elevated international normalized ratio from vitamin K supplement discontinuation.

Ann Pharmacother 2011;45:e2. View abstract. Mott A, Bradley T, Wright K, et al. Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials. Osteoporos Int 2019;30(8):1543-59. doi: 10.1007/s00198-019-04949-0. View abstract. Nagasawa Y, Fujii M, Kajimoto Y, et al. Vitamin K2 and serum cholesterol in patients on continuous ambulatory peritoneal dialysis.

Lancet 1998;351:724. View abstract. O'Connor EM, Grealy G, McCarthy J, Desmond A, Craig O, Shanahan F, Cashman KD. Effect of phylloquinone vitamin k1 K1) supplementation for 12 months on the indices of vitamin K status and bone health in adult patients with Crohn's disease. Br J Nutr. 2014;112(7):1163-74.

View abstract. Oikonomaki T, Papasotiriou M, Ntrinias T, et al. The effect of vitamin K2 supplementation on vascular calcification in haemodialysis patients: a 1-year follow-up randomized trial. Int Urol Nephrol 2019;51(11):2037-44. doi: 10.1007/s11255-019-02275-2. View abstract. Olson RE. Osteoporosis and vitamin K intake. Vitamin k1 J Clin Nutr 2000;71:1031-2.

View abstract. Ozdemir MA, Yilmaz K, Abdulrezzak U, Muhtaroglu S, Patiroglu T, Karakukcu M, Unal E. The efficacy of vitamin K2 and calcitriol combination on thalassemic osteopathy. J Pediatr Hematol Oncol. 2013;35(8):623-7. View abstract. Pinta F, Ponzetti A, Spadi R, Fanchini L, Zanini M, Mecca C, Sonetto C, Ciuffreda L, Racca P.

Pilot clinical trial on the efficacy of prophylactic use of vitamin K1-based cream (Vigorskin) to prevent cetuximab-induced skin rash in patients with metastatic colorectal cancer. Clin Colorectal Cancer.

2014;13(1):62-7. View abstract. Price PA. Vitamin K nutrition and postmenopausal osteoporosis. J Clin Invest vitamin k1. View abstract. Rahimi Sakak F, Moslehi N, Niroomand M, Mirmiran P. Glycemic control improvement in individuals with type 2 diabetes with vitamin K2 supplementation: a randomized controlled trial.

Eur J Nutr. 2020. View abstract. Reese AM, Farnett LE, Lyons RM, et al. Low-dose vitamin K to augment anticoagulation control. Vitamin k1 2005;25:1746-51. View abstract. Rejnmark L, Vestergaard P, Charles P, et al. No effect of vitamin K(1) intake on bone mineral density and fracture risk in perimenopausal women.

Osteoporos Int 2006;17:1122-32. View abstract. Renzulli P, Tuchschmid P, Eich G, et al. Early vitamin K deficiency bleeding after maternal phenobarbital intake: management of massive intracranial haemorrhage by minimal surgical intervention.

Eur J Pediatr 1998;157:663-5. View abstract. Robert D, Jorgetti V, Vitamin k1 M, et al. Does vitamin Vitamin k1 excess induce ectopic calcifications in hemodialysis patients? Clin Nephrol 1985;24:300-4. View abstract. Roche, Inc. Xenical package insert. Nutley, NJ. May 1999. Rombouts EK, Rosendaal FR. Van Der Meer FJ. Daily vitamin K supplementation improves anticoagulant stability. J Thromb Haemost 2007;5:2043-8.

View abstract. Rønn SH, Harsløf T, Oei L, Pedersen SB, Langdahl BL. The effect of vitamin MK-7 on vitamin k1 mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial. Osteoporos Int. 2021;32(1):185-191. View abstract. Sattler FR, Weitekamp MR, Ballard JO.

Potential for bleeding with the new beta-lactam antibiotics. Ann Intern Med 1986;105:924-31. View abstract. Schade RWB, van't Laar A, Majoor CLH, Jansen AP. A comparative study of the effects of cholestyramine and neomycin in the treatment of type II hyperlipoproteinemia. Acta Med Scand 1976;199:175-80. View abstract.

Schoon EJ, Muller MC, Vermeer C, et al. Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease? Gut 2001;48:473-7. View abstract. Schurgers LJ, Dissel PE, Spronk HM, et al. Role of vitamin K and vitamin K-dependent proteins in vascular calcification.

Z Kardiol 2001;90(suppl 3):57-63. View abstract. Schwarz KB, Goldstein PD, Witztum JL, et al. Fat-soluble vitamin concentrations in hypercholestrolemic children treated with colestipol. Pediatrics 1980;65:243-50. View abstract. Sconce E, Avery P, Wynne H, Kamali F.

Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood 2007;109:2419-23. View abstract. Sconce E, Khan T, Mason J, et al. Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation.

Thromb Haemost 2005;93:872-5. View abstract. Shea MK, Barger K, Booth SL, et al. Vitamin K status, cardiovascular disease, and all-cause mortality: a participant-level meta-analysis of 3 US cohorts. Am J Clin Nutr. 2020;111(6):1170-1177. View abstract. Shearer MJ, Bach A, Kohlmeier M. Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health. J Nutr 1996;126:1181S-6S. View abstract.

Shearer MJ. The roles of vitamins D and K in bone health and osteoporosis prevention. Proc Nutr Sci vitamin k1. View abstract. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis.

J Bone Miner Res 2000;15:515-21. View abstract. Shishavan NG, Gargari BP, Jafarabadi MA, Kolahi S, Haggifar S, Noroozi S. Vitamin K(1) supplementation did not alter inflammatory markers and clinical status in patients with rheumatoid arthritis. Int J Vitam Nutr Res. 2018;88(5-6):251-257. View abstract. Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet 1994;334:1372-3.

View abstract. Szulc P, Meunier PJ. Is vitamin K deficiency a risk factor for osteoporosis in Crohn's disease? Lancet 2001;357:1995-6. Vitamin k1 abstract. Tam DA Jr, Myer EC. Vitamin K-dependent coagulopathy in a child receiving anticonvulsant therapy. J Vitamin k1 Neurol 1996;11:244-6.

View abstract. Tamatani M, Morimoto S, Nakajima M, et al. Decreased circulating levels of vitamin K and 25-hydroxyvitamin D in osteopenic elderly men. Metabolism 1998;47:195-9. View abstract. Tarkesh F, Namavar Jahromi B, Hejazi N, Tabatabaee H. Beneficial health effects of Menaquinone-7 on body composition, glycemic indices, lipid profile, and endocrine markers in polycystic ovary syndrome patients.

Food Sci Nutr. vitamin k1. View abstract. Thorp JA, Gaston L, Caspers DR, Pal ML. Current concepts and controversies in the use of vitamin K. Drugs 1995;49:376-87. View abstract. Turck D, Bresson JL, Burlingame B, et al. Dietary reference values for vitamin K. EFSA J. 2017;15(5):e04780. View abstract. Van Steenbergen W, Vermylen J.

Reversible hypoprothrombinemia in a patient with primary biliary cirrhosis treated with rifampicin. Am J Gastroenterol 1995;90:1526-8.

View abstract. Vermeer C, Gijsbers BL, Craciun AM, et al. Effects of vitamin K on bone mass and bone metabolism. J Nutr 1996;126:1187S-91S. View abstract. Vermeer C, Schurgers LJ. A comprehensive review of vitamin K and vitamin K antagonists. Hematol Oncol Clin North Am 2000;14:339-53. View abstract. Vroonhof K, van Rijn HJ, van Hattum J. Vitamin K deficiency and bleeding after long-term use of cholestyramine.

Neth J Med 2003;61:19-21. View abstract. Weber P. Management of osteoporosis: is there a role for vitamin K? Int J Vitam Nutr Res 1997;67:350-356. View abstract. West RJ, Lloyd JK. The effect of cholestyramine on intestinal absorption. Gut 1975;16:93-8. View abstract. Wostmann BS, Knight PL.

Antagonism between vitamins A and K in the germfree rat. J Nutr. 1965;87(2):155-60. View abstract. Xiong Z, Liu Y, Chang T, et al.

Effect of vitamin K1 on survival of patients with chronic liver failure: A retrospective cohort study. Medicine (Baltimore).

2020;99(13):e19619. View abstract. Yonemura K, Kimura M, Miyaji T, Hishida A. Short-term effect of vitamin K administration on prednisolone-induced loss of bone mineral density in patients with chronic glomerulonephritis. Calcif Tissue Int 2000;66:123-8. View abstract. Yoshikawa H, Yamazaki S, Watanabe T, Abe T. Vitamin K deficiency in severely disabled children.

Vitamin k1 Child Neurol 2003;18:93-7. View abstract. Young DS. Effects of Drugs on Clinical Laboratory Tests 4th ed. Washington: AACC Press, 1995. CONDITIONS OF USE AND IMPORTANT INFORMATION: This information is meant to supplement, not replace advice from your doctor or healthcare provider and is not meant to cover all possible uses, precautions, interactions or adverse effects.

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Vitamin K structures.

Class identifiers Use Vitamin K deficiency, Warfarin overdose ATC code B02BA Biological target Gamma-glutamyl carboxylase Clinical data Drugs.com Medical Encyclopedia External links MeSH D014812 In Wikidata Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements.

[1] The human body requires vitamin K for post-synthesis modification of certain proteins that are vitamin k1 for blood coagulation (K from koagulation, German for "coagulation") or for controlling binding of calcium in bones and other tissues. [2] The complete synthesis involves final modification of these so-called "Gla proteins" by the enzyme gamma-glutamyl carboxylase that uses vitamin K as a cofactor.

Vitamin K is used in the liver as the intermediate VKH 2 to deprotonate a glutamate residue and then is reprocessed into vitamin K through a vitamin K oxide intermediate.

[3] The presence of uncarboxylated proteins indicates a vitamin K deficiency. Carboxylation allows them to bind ( chelate) calcium ions, which they cannot do otherwise.

[4] Without vitamin K, vitamin k1 coagulation is seriously impaired, and uncontrolled bleeding occurs. Research suggests that deficiency of vitamin K may also weaken bones, potentially contributing to osteoporosis, and may promote calcification of arteries and other soft tissues. [2] [4] [5] Chemically, the vitamin K family comprises 2- methyl- 1,4-naphthoquinone (3-) derivatives. Vitamin K includes two natural vitamers: vitamin K 1 ( phylloquinone) and vitamin K 2 ( menaquinone).

[4] Vitamin K 2, in turn, consists of a number of related chemical subtypes, with differing lengths of carbon side chains made of isoprenoid groups of atoms. The two most studied ones are menaquinone-4 (MK-4) and menaquinone-7 (MK-7). Vitamin K 1 is made by plants, and is found in highest amounts in green leafy vegetables, because it is directly involved in photosynthesis. 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 2, variant MK-4. Bacteria in the gut flora can also convert K 1 into MK-4. All forms of K 2 other than MK-4 can only be produced by bacteria, which use these during anaerobic respiration. Vitamin K 3 ( menadione), a synthetic form of vitamin K, was used to treat vitamin K deficiency, but because it interferes with the function of glutathione, it is no longer used this way in human nutrition.

[2] Contents • 1 Definition • 2 Dietary recommendations • 2.1 Fortification • 3 Sources • 3.1 Vitamin K 1 • 3.2 Vitamin K 2 • 4 Vitamin deficiency • 5 Medical vitamin k1 • 5.1 Treating vitamin deficiency in newborns • 5.2 Managing warfarin therapy • 5.3 Treating rodenticide poisoning • 5.4 Methods of assessment • 5.5 Side effects • 6 Non-human uses • 7 Chemistry • 7.1 Conversion of vitamin K 1 to vitamin K 2 • 8 Physiology • 8.1 Absorption • 9 Biochemistry • 9.1 Function in animals • 9.2 Gamma-carboxyglutamate proteins • 9.3 Function in plants • 9.4 Function in bacteria • 10 History • 11 Research • 11.1 Osteoporosis • 11.2 Cardiovascular health • 11.3 Other • 12 References • 13 Further reading • 14 External links Definition [ edit ] Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements.

"Vitamin K" include several chemical compounds. These are similar in structure in that they share a quinone ring, but differ in the length and degree of saturation of the carbon tail and the number of repeating isoprene units in the side chain (see figures in Chemistry section).

Plant-sourced forms are primarily vitamin K 1. Animal-sourced foods are primarily vitamin K 2. [1] [6] [7] Vitamin K has several roles: an essential nutrient absorbed from food, a product synthesized and marketed as part of a multi-vitamin or as a single-vitamin dietary supplement, and a prescription medication for specific purposes.

[1] Dietary recommendations [ edit ] The US National Academy of Medicine does not distinguish between K 1 and K 2 – both are counted as vitamin K. When recommendations were last updated in 1998, sufficient information was not available to establish an estimated average requirement or recommended dietary allowance, terms that exist for most vitamins.

In instances such as these, the academy defines adequate intakes (AIs) as amounts that appear to be sufficient to maintain good health, 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 older are 90 and 120 μg/day, respectively, for pregnancy is 90 μg/day, and for lactation is 90 μg/day.

For infants up to 12 months, the AI is 2.0–2.5 μg/day; for children ages 1–18 years the AI increases with age from 30 to 75 μg/day. As for safety, the academy sets tolerable upper intake levels (known as "upper limits") for vitamins and minerals when evidence is sufficient. Vitamin K has no upper limit, as human data for adverse effects from high doses are not sufficient.

[5] In the European Union, adequate intake is defined the same way as in the US. For women and men over age 18 the adequate intake is set vitamin k1 70 μg/day, for pregnancy 70 μg/day, and for lactation 70 μg/day.

For children ages 1–17 years, adequate intake values increase with age from 12 to 65 μg/day. [8] Japan set adequate intakes for adult women at 65 μg/day and for men at 75 μg/day. [9] The European Union and Japan also reviewed vitamin k1 and concluded – as had the Vitamin k1 States – that there was insufficient evidence to set an upper limit for vitamin K.

[9] [10] For US food and dietary supplement labeling purposes, the amount in a serving is expressed as a percentage of daily value. For vitamin K labeling purposes, 100% of the daily value was 80 μg, but on 27 May 2016 it was revised upwards to 120 μg, to bring it into agreement with the highest value for adequate intake. [11] [12] Compliance with the updated labeling regulations was required by 1 January 2020 for manufacturers with US$10 million or more in annual food sales, and by 1 January 2021 for manufacturers with lower volume food sales.

[13] [14] A table of the old vitamin k1 new adult daily values is provided at Reference Daily Intake. Fortification [ edit ] According to the Global Fortification Data Exchange, vitamin K deficiency is so rare that no countries require that foods vitamin k1 fortified. [15] The World Health Organization vitamin k1 not have recommendations on vitamin K fortification.

[16] Sources [ edit ] Vitamin K 1 is primarily from plants, especially leafy green vegetables. Small amounts are provided by animal-sourced foods. Vitamin K 2 is primarily from animal-sourced foods, with poultry and eggs much better sources than beef, pork or fish.

[7] One exception to the latter is nattō, which is made from bacteria-fermented soybeans. It is a rich food source of vitamin K 2 variant MK-7, made by the bacteria.

[17] Vitamin K 1 [ edit ] Plant-sourced [7] Amount K 1 (μg / measure) Collard greens boiled, drained, 1⁄ 2 cup 530 Spinach boiled, drained, 1⁄ 2 cup 445 Turnip greens boiled, drained, 1⁄ 2 cup 425 Spinach raw, 1 cup 145 Brussels sprouts boiled, drained, 1⁄ 2 cup 110 Kale raw, 1 cup 82 Broccoli boiled, drained, 1⁄ 2 cup 81 Asparagus boiled, drained, 4 spears 48 Kiwifruit peeled, sliced, 1⁄ 2 cup 36 Chinese cabbage cooked, 1⁄ 2 cup 29 Blueberries frozen, 1⁄ 2 cup 21 Carrots raw, chopped, 1 cup 17 Plant-sourced [7] Amount Vitamin k1 1 (μg / measure) Hazelnuts chopped, 1 cup 16 Grapes, 1⁄ 2 cup 11 Tomato products, 1 cup 9.2 Olive oil, 1.0 tablespoon 8.1 Zucchini boiled, drained, 1.0 cup 7.6 Mangos pieces, 1.0 cup 6.9 Pears, pieces, 1.0 vitamin k1 6.2 Potato baked, including skin, one 6.0 Sweet potato baked, one 2.6 Bread whole wheat, 1 slice 2.5 Bread white, 1 slice 2.2 Main article: Vitamin K deficiency Because vitamin K aids mechanisms for blood clotting, its deficiency may lead to reduced blood clotting, and in severe vitamin k1, can result in reduced clotting, increased bleeding, and increased prothrombin time.

[2] [5] Normal diets are usually not deficient in vitamin K, indicating that deficiency is uncommon in healthy children and adults. [4] An exception may be infants who are at an increased risk of deficiency regardless of the vitamin status of the mother during pregnancy and breast feeding due to poor transfer of the vitamin to the placenta and low amounts of the vitamin in breast milk.

[18] Secondary deficiencies can occur in people who consume adequate amounts, but have malabsorption conditions, such as cystic fibrosis or chronic pancreatitis, and in people who have liver damage or disease. [2] Secondary vitamin K deficiency can also occur in people who have a prescription for a vitamin K antagonist drug, such as warfarin.

[2] [4] A drug associated with increased risk of vitamin K deficiency is cefamandole, although the mechanism is unknown. [22] Medical uses [ edit ] Treating vitamin deficiency in newborns [ edit ] Vitamin K is given as an injection to newborns to prevent vitamin K deficiency bleeding. [18] The blood clotting factors of newborn babies are roughly 30–60% that of adult values; this appears to be a consequence of poor transfer of the vitamin across the placenta, and thus low fetal plasma vitamin K.

[18] Occurrence of vitamin K deficiency bleeding in vitamin k1 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. Human milk contains 0.85–9.2 μg/L (median 2.5 μg/L) of vitamin K 1, while infant formula is formulated in range of 24–175 μg/L.

[18] Late onset vitamin k1, with onset 2 to 12 weeks after birth, can be a consequence of exclusive breastfeeding, especially if there was no preventive treatment.

[18] Late onset prevalence reported at 35 cases per 100,000 live births in infants who had not received prophylaxis at or shortly after birth.

[23] Vitamin K deficiency bleeding occurs more frequently in the Asian population compared to the Caucasian population. [18] Bleeding in infants due to vitamin K deficiency can be severe, leading to hospitalization, brain damage, and death. Intramuscular injection, typically given shortly after birth, is more effective in preventing vitamin K deficiency bleeding than oral administration, which calls for weekly dosing up to three months of age.

[18] Managing warfarin therapy [ edit ] Warfarin is an anticoagulant drug. It functions by inhibiting an enzyme that is responsible for recycling vitamin K to a functional state. As a consequence, proteins that should be modified by vitamin K are not, including proteins essential to blood clotting, and are thus not functional.

[24] The purpose of the drug is to reduce risk of inappropriate blood vitamin k1, which can have serious, potentially fatal consequences. [2] The proper anticoagulant action of warfarin is a function of vitamin K intake and drug dose. Due to differing absorption of the drug and amounts of vitamin K in the diet, dosing must be monitored and individualized for each patient.

[25] Some foods are so high in vitamin K 1 that medical advice is to avoid those (examples: collard greens, spinach, turnip greens) entirely, and for foods with a modestly high vitamin content, keep consumption as consistent as possible, so that the combination of vitamin intake and warfarin keep the anti-clotting activity in the therapeutic range. [26] Vitamin K is a treatment for bleeding events caused by overdose of the drug. [27] The vitamin can be administered by mouth, intravenously or subcutaneously.

[27] Oral vitamin K is used in situations when a person's International normalised ratio is greater than 10 but there is no active vitamin k1. [26] [28] The newer anticoagulants apixaban, dabigatran and rivaroxaban are not vitamin K antagonists. [29] Treating rodenticide poisoning [ edit ] Coumarin is used in the pharmaceutical industry as a precursor reagent in the synthesis of a number of synthetic anticoagulant pharmaceuticals.

[30] One subset, 4-hydroxycoumarins, act as vitamin K antagonists. They block the regeneration and recycling of vitamin K. Some of the 4-hydroxycoumarin vitamin k1 class of chemicals are designed to have high potency and long residence times in the body, and these are used specifically as second generation rodenticides ("rat poison").

Death occurs after a period of several days to two weeks, usually from internal hemorrhaging. [30] For humans, and for animals that have consumed either the rodenticide or rats poisoned by the rodenticide, treatment is prolonged administration of large amounts of vitamin K.

[31] [32] This dosing must sometimes be continued for vitamin k1 to nine months in cases of poisoning by " superwarfarin" rodenticides such as brodifacoum.

Oral vitamin K 1 is preferred over other vitamin K 1 routes of administration because it has fewer side effects. [33] Methods of assessment [ edit ] An increase in prothrombin time, a coagulation assay, has been used as an indicator of vitamin K status, but it lacks sufficient sensitivity and specificity for this application.

[34] Serum phylloquinone is the most commonly used marker of vitamin K status. Concentrations <0.15 µg/L are indicative of deficiency. Disadvantages include exclusion of the other vitamin K vitamers and interference from recent dietary intake. [34] Vitamin K is required for the gamma-carboxylation of specific glutamic acid residues within the Gla domain of the 17 vitamin K–dependent proteins. Thus, a rise in uncarboxylated versions of these proteins is an indirect but sensitive and specific marker for vitamin K deficiency.

If uncarboxylated prothrombin is being measured, this "Protein induced by Vitamin K Absence/antagonism (PIVKA-II)" is elevated in vitamin K deficiency. The test is used to assess risk of vitamin K–deficient bleeding in newborn infants.

[34] Osteocalcin is involved in calcification of bone tissue. The ratio of uncarboxylated osteocalcin to carboxylated osteocalcin increases with vitamin K deficiency. Vitamin K2 has been shown to lower this ratio and improve lumbar vertebrae bone mineral density.

[35] Matrix Gla protein must undergo vitamin K dependent phosphorylation and carboxylation. Elevated plasma concentration of dephosphorylated, uncarboxylated MGP is indicative of vitamin K deficiency.

[36] Side effects [ edit ] No known toxicity is associated with high oral doses of the vitamin K 1 or (vitamin K 2) forms of vitamin K, so regulatory agencies from US, Japan and European Union concur that no tolerable upper intake levels needs to be set.

[5] [9] [10] However, vitamin K 1 has been associated with severe adverse reactions such as bronchospasm and cardiac arrest when given intravenously. The reaction is described as a nonimmune-mediated anaphylactoid reaction, with incidence of 3 per 10,000 treatments. The majority of reactions occurred when polyoxyethylated castor oil was used as the solubilizing agent. [37] Non-human uses [ edit ] Forms not found in nature, and thus not "vitamins", are menadione and 4-amino-2-methyl-1-naphthol ("K 5").

Menadione, a synthetic compound sometimes referred to as vitamin K 3, is used in the pet food industry because once consumed it is converted to vitamin K 2. [38] The US Food and Drug Administration has banned this form from sale as a human dietary supplement because large doses have been shown to cause allergic reactions, hemolytic anemia, and cytotoxicity in liver cells. [2] Research with K 5 suggests it may inhibit fungal growth in fruit juices.

[39] Chemistry [ edit ] Vitamin K 2 (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 vitamin k1 enzymes normally produce menaquinone-4 from plant phylloquinone. The structure of phylloquinone, Vitamin K 1, is marked by the presence of a phytyl sidechain. [5] Vitamin K 1 has an (E) trans double bond responsible for its biological activity, and two chiral centers on the phytyl sidechain.

[40] Vitamin K 1 appears as a yellow viscous liquid at rom temperature due to its absorption of violet light in the UV-Vis Spectra. [41] The structures of menaquinones, vitamin K 2, are marked by the polyisoprenyl side chain present in the molecule that can contain four to 13 isoprenyl units. MK-4 is the most common form. [5] The large size of Vitamin K 1 gives many different peaks in mass spectroscopy, most of which involve derivatives of the naphthoquinone ring base and the alkyl side chain.

[42] Main article: Vitamin K 2 In animals, the MK-4 form of vitamin K 2 is produced by conversion of vitamin K 1 in the testes, pancreas, and arterial walls. [21] 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 [43] and in parenterally administered K 1 in rats.

[44] [45] There is evidence that the conversion proceeds by removal of the phytyl tail of K 1 to produce menadione (also referred to as vitamin K 3) as an intermediate, which is then prenylated to produce MK-4.

{INSERTKEYS} [46] Physiology [ edit ] In animals, vitamin K 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. [47] 17 human proteins with Gla domains have been discovered; 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 [48] • Bone metabolism: osteocalcin, matrix Gla protein (MGP), [49] periostin, [50] and Gla-rich protein.

[51] [52] • Vascular biology: Matrix Gla protein, growth arrest – specific protein 6 (Gas6) [53] • Unknown functions: proline-rich γ-carboxyglutamyl proteins 1 and 2, and transmembrane γ-carboxy glutamyl proteins 3 and 4. [54] Absorption [ edit ] Vitamin K is absorbed through the jejunum and ileum in the small intestine. The process requires bile and pancreatic juices. Estimates for absorption are on the order of 80% for vitamin K 1 in its free form (as a dietary supplement) but much lower when present in foods.

For example, the absorption of vitamin K from kale and spinach – foods identified as having a high vitamin K content – are on the order of 4% to 17% regardless of whether raw or cooked. [4] Less information is available for absorption of vitamin K 2 from foods. [4] [5] The intestinal membrane protein Niemann–Pick C1-like 1 (NPC1L1) mediates cholesterol absorption.

Animal studies show that it also factors into absorption of vitamins E and K 1. [55] The same study predicts potential interaction between SR-BI and CD36 proteins as well.

[55] The drug ezetimibe inhibits NPC1L1 causing a reduction in cholesterol absorption in humans, and in animal studies, also reduces vitamin E and vitamin K 1 absorption. An expected consequence would be that administration of ezetimibe to people who take warfarin (a vitamin K antagonist) would potentiate the warfarin effect. This has been confirmed in humans. [55] Biochemistry [ edit ] Function in animals [ edit ] In both cases R represents the isoprenoid side chain.

Vitamin K is distributed differently within animals depending on its specific homologue. Vitamin K 1 is mainly present in the liver, heart and pancreas, while MK-4 is better represented in the kidneys, brain and pancreas. The liver also contains longer chain homologues MK-7 to MK-13.

[56] The function of vitamin K 2 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. [57] Within the cell, vitamin K participates in a cyclic process.

The vitamin undergoes electron reduction to a reduced form called vitamin K hydroquinone, catalyzed by the enzyme vitamin K epoxide reductase (VKOR).

[58] Another enzyme then oxidizes vitamin K hydroquinone to allow carboxylation of Glu to Gla; this enzyme is called gamma-glutamyl carboxylase [59] 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 restored to vitamin K by VKOR. The reduction and subsequent reoxidation of vitamin K coupled with carboxylation of Glu is called the vitamin K cycle. [60] Humans are rarely deficient in vitamin K because, in part, vitamin K 2 is continuously recycled in cells.

[61] Warfarin and other 4-hydroxycoumarins block the action of VKOR. [24] 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 cannot 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 underdose and overdose. [25] 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 protein C and protein 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, and the four transmembrane Gla proteins, the function of which is at present unknown. The Gla domain is responsible for high-affinity binding of calcium ions (Ca 2+) to Gla proteins, which is often necessary for their conformation, and always necessary for their function.

[57] 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.

[62] Another interesting class of invertebrate Gla-containing proteins is synthesized by the fish-hunting snail Conus geographus. [63] 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. [64] Function in plants [ edit ] Vitamin K 1 is an important chemical in green plants, where it functions as an electron acceptor in photosystem I during photosynthesis. [65] For this reason, vitamin K 1 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.

[7] [65] Function in bacteria [ edit ] Many bacteria, including Escherichia coli found in the large intestine, can synthesize vitamin K 2 (MK-7 up to MK-11), [66] but not vitamin K 1. Green algae and some species of cyanobacteria (sometimes referred to as blue-green algae) are able to synthesize vitamin K 1. [65] In the vitamin K 2 synthesizing bacteria, menaquinone transfers two electrons between two different small molecules, during oxygen-independent metabolic energy production processes ( anaerobic respiration).

[67] 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 as 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.

[67] 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, 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.

[67] History [ edit ] In 1929, Danish scientist Henrik Dam investigated the role of cholesterol by feeding chickens a cholesterol-depleted diet. [68] He initially replicated experiments reported by scientists at the Ontario Agricultural College. [69] 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. [70] 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. [71] Dam and Doisy shared the 1943 Nobel Prize for medicine for their work on vitamin K 1 and K 2 published in 1939. Several laboratories synthesized the compound(s) in 1939. [72] 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). [73] 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.

[74] The precise function of vitamin K was not discovered until 1974, when prothrombin, a blood coagulation protein, was confirmed to be vitamin K dependent. When the vitamin is present, prothrombin has amino acids near the amino terminus of the protein as γ-carboxyglutamate instead of glutamate, and is able to bind calcium, part of the clotting process.

[75] Research [ edit ] Osteoporosis [ edit ] Vitamin K is required for the gamma-carboxylation of osteocalcin in bone. [76] The risk of osteoporosis, assessed via bone mineral density and fractures, was not affected for people on warfarin therapy – a vitamin K antagonist. [77] Higher dietary intake of vitamin K 1 may modestly decrease the risk of fractures. [78] However, there is mixed evidence to support a claim that vitamin K supplementation reduces risk of bone fractures.

[4] [76] [79] For women who were post-menopausal and for all people diagnosed with osteoporosis, supplementation trials reported increases in bone mineral density, a reduction to the odds of any clinical fractures but no significant difference for vertebral fractures. [79] There is a subset of literature on supplementation with vitamin K 2 MK-4 and bone health. A meta-analysis reported a decrease in the ratio of uncarboxylated osteocalcin to carboxylated, an increase in lumbar spine bone mineral density, but no significant differences for vertebral fractures.

[35] Cardiovascular health [ edit ] 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. [4] In humans, Keutel syndrome is a rare recessive genetic disorder associated with abnormalities in the gene coding for MGP and characterized by abnormal diffuse cartilage calcification.

[80] 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. [4] In meta-analyses of population studies, low intake of vitamin K was associated with inactive MGP, arterial calcification [81] and arterial stiffness.

[82] [83] Lower dietary intakes of vitamin K 1 and vitamin K 2 were also associated with higher coronary heart disease. [36] [84] When blood concentration of circulating vitamin K 1 was assessed there was an increased risk in all cause mortality linked to low concentration. [85] [86] In contrast to these population studies, a review of randomized trials using supplementation with either vitamin K 1 or vitamin K 2 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. [87] Other [ edit ] 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. [4] From a review of observational trials, long-term use of vitamin K antagonists as anticoagulation therapy is associated with lower cancer incidence in general.

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"Vitamin K status, cardiovascular disease, and all-cause mortality: a participant-level meta-analysis of 3 US cohorts". Am J Clin Nutr. 111 (6): 1170–77. doi: 10.1093/ajcn/nqaa082. PMC 7266692. PMID 32359159. • ^ Vlasschaert C, Goss CJ, Pilkey NG, McKeown S, Holden RM (September 2020). "Vitamin K Supplementation for the Prevention of Cardiovascular Disease: Where Is the Evidence?

A Systematic Review of Controlled Trials". Nutrients. 12 (10): 2909. doi: 10.3390/nu12102909. PMC 7598164. PMID 32977548. • ^ Shurrab M, Quinn KL, Kitchlu A, Jackevicius CA, Ko DT (September 2019). "Long-Term Vitamin K Antagonists and Cancer Risk: A Systematic Review and Meta-Analysis".

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doi: 10.1097/MD.0000000000013489. PMC 6310569. PMID 30544443. • ^ Kristensen KB, Jensen PH, Skriver C, Friis S, Pottegård A (April 2019). "Use of vitamin K antagonists and risk of prostate cancer: Meta-analysis and vitamin k1 case-control study" (PDF). Int. J. Cancer. 144 (7): 1522–1529. doi: 10.1002/ijc.31886. PMID 30246248. S2CID 52339455. Further reading [ edit ] • "Vitamin K: Another Reason to Eat Your Greens" (PDF). Agricultural Research.

48 (1). January 2000. ISSN 2169-8244. External links [ edit ] Wikimedia Commons has media related to Vitamin K. Look up vitamin k in Wiktionary, the free dictionary. • "Vitamin K". Drug Information Portal. U.S. National Library of Medicine. • "Phylloquinone". Drug Information Portal. U.S. National Library of Medicine. • "Phytomenadione". Drug Information Portal.

U.S. National Library of Medicine. • "Vitamin K2". Drug Information Portal. U.S. National Library of Medicine. • "Menadione". Drug Information Portal. U.S. National Library of Medicine. • D 2 • Ergosterol • Ergocalciferol # • D 3 • 7-Dehydrocholesterol • Previtamin D 3 • Cholecalciferol # • 25-hydroxycholecalciferol • Calcitriol (1,25-dihydroxycholecalciferol) • Calcitroic acid • D 4 • Dihydroergocalciferol • D 5 • D analogues • Alfacalcidol • Dihydrotachysterol • Calcipotriol • Tacalcitol • Paricalcitol E • B 1 vitamin k1 Thiamine # • B 1 analogues • Acefurtiamine • Allithiamine • Benfotiamine • Fursultiamine • Octotiamine • Prosultiamine • Sulbutiamine • B 2 • Riboflavin # • B 3 • Niacin • Niacinamide # • B 5 • Pantothenic acid • Dexpanthenol • Pantethine • B 6 • Pyridoxine #, Pyridoxal phosphate • Pyridoxamine • Pyritinol • B 7 • Biotin • B 9 • Folic acid # • Dihydrofolic acid • Folinic acid • Levomefolic acid • B 12 • Adenosylcobalamin • Cyanocobalamin • Hydroxocobalamin # • Methylcobalamin C • intrinsic: IX/ Nonacog alfa • VIII/ Damoctocog alfa pegol/ Efmoroctocog alfa/ Moroctocog alfa/ Susoctocog alfa/ Turoctocog alfa • extrinsic: VII/ Eptacog alfa • common: Vitamin k1 • II/Thrombin • I/Fibrinogen • XIII/ Catridecacog • combinations: Prothrombin complex concentrate (II, VII, IX, X, protein C and S) Other systemic Hidden categories: • CS1: long volume value • Source attribution • Articles with short description • Vitamin k1 description is different from Wikidata • Good articles • Use dmy dates from August 2021 • Articles to be expanded from January 2021 • Commons category link is on Wikidata • Articles with BNF identifiers • Articles with J9U identifiers • Articles with LCCN identifiers • Vitamin k1 with NDL identifiers • Afrikaans • العربية • Asturianu • Azərbaycanca • تۆرکجه • বাংলা • Bân-lâm-gú • Български • Bosanski • Català • Čeština • Dansk • Deutsch • ދިވެހިބަސް • Eesti • Ελληνικά • Español • Esperanto • Euskara • فارسی • Français • Galego • 한국어 • Հայերեն • हिन्दी • Hrvatski • Bahasa Indonesia • Íslenska • Italiano • עברית • Jawa • ქართული • Кыргызча • Latviešu • Lietuvių • മലയാളം • मराठी • Bahasa Melayu • မြန်မာဘာသာ • Nederlands • नेपाली • 日本語 • Norsk bokmål • Norsk nynorsk • Occitan • Polski • Português • Română • Русский • Simple English • Slovenščina • Српски / srpski • Srpskohrvatski / српскохрватски • Sunda • Suomi • Svenska • தமிழ் • ไทย • Türkçe • Тыва дыл • Українська • Vitamin k1 Việt • 吴语 • 粵語 • 中文 Edit links • This page was last edited on 7 April 2022, at 19:10 (UTC).

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Vitamin K and blood clotting




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