doi: 10.1016/S0083-6729(07)00013-1.Author information1Professor of Medicine, Director Jefferson Center for Vascular Diseases, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.AbstractVitamin K was discovered in the 1930s during cholesterol metabolism experiments in chickens. It is a fat-soluble vitamin which occurs naturally in plants as phylloquinone (vitamin K1) and is produced by gram-negative bacteria in the human gastrointestinal tract as menaquinone (vitamin K2). This vitamin was found to be essential for normal functioning of hemostasis. In addition, a number of clinical conditions in which vitamin K deficiency was found to be the underlying pathophysiologic problem were discovered. These conditions include hemorrhagic disease of the newborn, obstructive jaundice, and malabsorption syndromes. The importance of this vitamin has become more apparent with the discovery of the anticoagulant warfarin which is a vitamin K antagonist. There are millions of patients on this therapy for a variety of thrombogenic conditions such as atrial fibrillation, deep vein thrombosis, pulmonary embolism, and prosthetic cardiac valves.
The wide use of this narrow therapeutic index drug has resulted in significant risk for major bleeding. Vitamin K serves as one of the major reversing agent for patients over-anticoagulated with warfarin. In the past few years, research has focused on new areas of vitamin K metabolism, which include bone and endovascular metabolism; cell growth, regulation, migration, and proliferation; cell survival, apoptosis, phagocytosis, and adhesion. These new areas of research highlight the significance of vitamin K but raise new clinical questions for patients who must be maintained on long-term warfarin therapy.PMID: 18374199 DOI: 10.1016/S0083-6729(07)00013-1 [Indexed for MEDLINE] Publication typeReviewMeSH termsAnticoagulants/pharmacologyBlood Coagulation Factors/biosynthesisGlutamic Acid/metabolismHemorrhageHumansThrombosis*Vitamin K/physiology*Vitamin K/therapeutic useWarfarin/pharmacologySubstancesAnticoagulantsBlood Coagulation FactorsVitamin KGlutamic AcidWarfarinFull Text SourcesElsevier ScienceMedicalThrombosis - Genetic AllianceBlood Clots - MedlinePlus Health InformationVitamin K - MedlinePlus Health InformationMiscellaneousGLUTAMIC ACID HYDROCHLORIDE - Hazardous Substances Data BankWARFARIN - Hazardous Substances Data BankNCI CPTAC Assay Portal
side effects, nutrient depletions, herbal interactions and health notes: Data provided by Applied Health • Avoid supplementing high dosages of vitamin A (over 10000 IU/day), or vitamin E (over 400 IU/day) with this medication.1• More than 5 gms (5,000 mg) of vitamin C may reduce the absorption of Warfarin.2• Absorption and activity of Warfarin may be decreased by iron, magnesium, and zinc. These minerals should be taken at least two hours apart from this medication.3• If you are taking NSAIDS and Warfarin, you should consult with a physician before using chondroitin sulfate.4• More than 60 grams of onions (2 ounces) may affect the activity of Warfarin.5• Avoid avocado with warfarin.6• Vitamin K and warfarin are co-dependent. Vitamin K levels must be kept at constant levels while taking warfarin.7• Coumadin may also be affected by CoQ10, which creates a similar action as vitamin K.8• Taking high doses of Grapefruit juice with Warfarin can produce high INRs.9• The following herbs may contribute to blood-thinning, and should not be used with Warfarin: Angelica, anise, arnica, asafoetida, bogbean, boldo, danshen, fenugreek
, feverfew, garlic, ginger, ginkgo, ginseng (Panax), horse chestnut, licorice, meadowsweet, prickly ash, passionflower, poplar, quassia, red clover, turmeric, and willow.10• Warfarin absorption may be affected by daily use of the following herbs: Catnip, Comfrey, Gentian, Hops, Mullein, Peppermint, or Slippery elm.11 References1 Wells, PS et al., Interactions of Warfarin with drugs and food. Ann. Int. Med. 1994, 121:676-683.1 Pronsky, Z Food Medication Interactions, 11th edition, 19992 Wells, PS et al., Interactions of Warfarin with drugs and food. Ann. Int. Med. 1994, 121:676-683.2 Harris JE. Interaction of dietary factors with oral anticoagulants: Review and applications. J Am Dietet Assoc 1995;95:580-84 [review].3 Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 284.4 Chavez, M: Glucosamine sulfate and chondroitin sulfates. Hospital Pharmacy, 1997, 52(9): 1,275-1,285.5 Menon, I.S. et al: Effect of onions on blood fibrinolytic activity. BMJ, 1968,3:351.5 Pronsky, Z Food Medication Interactions, 11th edition, 19995 Holt GA. Food & Drug Interactions.
Chicago: Precept Press, 1998, 284.6 Blickstein, D et al, "Warfarin antagonism by avocado", 1991, The Lancet 337:914-915.7 Facts and Comparisons, Clinisphere 2.0, Wolters Kluwer Company, 20007 Pronsky, Z Food Medication Interactions, 11th edition, 19997 Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 286.8 United States Pharmacopeia Drug Index (USPDI). 8th ed. Rockville, Md: US Pharmacopeial Convention, Inc; J Am Dietet Assoc 1995;95:580-84 [review].8 Landbo C & Almdal TP [Interaction between warfarin and coenzyme Q10.] Ugeskr Laeger, 1998 May, 160:22, 3226-7.8 Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet 1994;344:1372-73 [letter].9 Bartle, W. Grapefruit juice might still be factor in warfarin response (letter). American Journal of Health-System Pharmacy 1999; 56 (April 1): 676.9 Sullivan D, et al. Grapefruit juice and the response to warfarin. American Journal of Health-System Pharmacy 1998; 55: 1581-1583.10 Newall CA, Anderson LA, Phillipson JD.
Herbal Medicines A Guide for Health-care Professionals. London: The Pharmaceutical Press, 1996.10 Gadkari JV, Joshi VD. Effect of ingestion of raw garlic on serum cholesterol level, clotting time and fibrinolytic activity in normal subjects. J Postgrad Med 1991;37:128-31.10 Burnham BE. Garlic as a possible risk for postoperative bleeding. Plast-Reconst-Surg 1995;95:213.10 Kleijnen J, Knipschild P. Ginkgo biloba. Lancet 1992;340:1136-39.10 Pronsky, Z Food Medication Interactions, 11th edition, 199910 Brinker, F Herb Contraindications and Drug Interactions, Eclectic Medical Publications, 199810 PDR for Herbal Medicines, 2nd edition, Medical Economics Company, 200011 Tyler, V.E.: The Honest Herbal. Haworth, Binghampton, NY, 1993.11 Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health-Syst Pharm 1997;54:692-93.11 Yu CM, Chan JCN, Sanderson JE. Chinese herbs and warfarin potentiation by "danshen." J Intern Med 1997;241:337-39.11 Tatro D, ed. Anticoagulants-quinine derivatives.
In Drug Interaction Facts. St. Louis, MO: Facts and Comparisons, Jul 1993.11 Harris JE. Interaction of dietary factors with oral anticoagulants: Review and application. J Am Diet Assoc 1995;95:580-84 [review]. Want more special reports like this e-mailed to you when they're available? Click here for free e-mail alerts. Share this Special Report by linking to it Copy and paste the following HTML code into any web page: Warfarin Sodium nutritional deficiencies database The information in Drug Watch is provided as a courtesy to NewsTarget readers by Applied Health Solutions in cooperation with Healthway Solutions. Although the information is presented with scientific references, we do not wish to imply that this represents a comprehensive list of considerations about any specific drug, herb or nutrient. Nor should this information be considered a substitute for the advice of your doctor, pharmacist, or other healthcare practitioner.