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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.
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjectsFrom 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
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| Copyright © 2004 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
-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) 
