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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2682-2689. Prepublished online as a Blood First Edition Paper on July 1, 2004; DOI 10.1182/blood-2004-04-1525. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1525v1 104/9/2682    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schurgers, L. J. Articles by Vermeer, C. Search for Related Content PubMed PubMed Citation Articles by Schurgers, L. J. Articles by Vermeer, C. Related Collections Clinical Trials and Observations Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects Leon J. Schurgers, Martin J. Shearer, Karly Hamulyák, Elisabeth Stöcklin, and Cees Vermeer From the Cardiovascular Research Institute Maastricht and VitaK BV, Maastricht, The Netherlands; the Centre for Haemostasis and Thrombosis, St Thomas' Hospital, London, United Kingdom; the Department of Haematology, University Hospital Maastricht, The Netherlands; and DSM Nutritional Products (registered as Roche Vitamins Ltd), Basel, Switzerland. Oral anticoagulants exert their effect by blocking the utilization of vitamin K, yet little is known about competitive aspects of their interaction with dietary vitamin K. We carried out systematic dose-response studies in healthy volunteers who had been stably anticoagulated and maintained on their individualized doses for 13 weeks. First, we studied the response to weekly incremental doses (50 µg-500 µg) of vitamin K1 supplements (K1) taken daily for 7 days. The threshold K1 dose causing a statistically significant lowering of the INR was 150 µg/day. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 µg/day. Circulating undercarboxylated osteocalcin did not decrease until 300 µg K1/day compared with 100 µg K1/day for undercarboxylated FII, suggesting differential antidotal effects on bone and hepatic -carboxylation. Next, we tested the response to vitamin K-rich food items. The short-lived response after meals of spinach and broccoli suggested an inefficient bioavailability from these 2 sources. We conclude that short-term variability in intake of K1 is less important to fluctuations in the international normalized ratio (INR) than has been commonly assumed and that food supplements providing 100 µg/day of vitamin K1 do not significantly interfere with oral anticoagulant therapy. (Blood. 2004;104:2682-2689) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. J. Schurgers, K. J. F. Teunissen, K. Hamulyak, M. H. J. Knapen, H. Vik, and C. Vermeer Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7 Blood, April 15, 2007; 109(8): 3279 - 3283. [Abstract] [Full Text] [PDF] E. Sconce, P. Avery, H. Wynne, and F. Kamali Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin Blood, March 15, 2007; 109(6): 2419 - 2423. [Abstract] [Full Text] [PDF]

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