Submitted April 21, 2004
Accepted June 21, 2004
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 Hamulyak, Elisabeth Stoecklin, and Cees Vermeer
Cardiovascular Research Institute, University Maastricht, Maastricht, The Netherlands
Haemophilia Reference Centre, St. Thomas' Hospital, London, United Kingdom
Department of Haematology, University Hospital Maastricht, Maastricht, The Netherlands
Roche Vitamins Ltd, DSM Nutritional Products, Basel, Switzerland
* Corresponding author; email: l.schurgers{at}bioch.unimaas.nl.
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 (50-500 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/d. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 µg/d. Circulating undercarboxylated osteocalcin did not decrease until 300 µg K1/d compared to 100 µg K1/d 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 two sources. We conclude that short-term variability in intakes of K1 is less important to fluctuations in INR than has been commonly assumed and that food supplements providing 100 µg/d of vitamin K1 do not significantly interfere with oral anticoagulant therapy.
