Effect of low-dose supplements of menaquinone-7 (vitamin K2) on the stability of oral anticoagulant treatment: Dose-response relationship in healthy volunteers

Abstract

Background and Objective: Despite the worldwide use of vitamin K antagonists (VKAs), there is limited knowledge of the influence of dietary vitamin K on anticoagulation control. In view of the increasing nutraceutical availability of menaquinone-7 (MK-7; vitamin K2) and its promotion for bone and cardiovascular health, it is important to determine the posology for the interference of supplemental MK-7 with VKA therapy. Patients: Eighteen healthy men and women were anticoagulated for 4 weeks with acenocoumarol, and 15 of them attained a target International Normalized Ratio (INR) of 2.0. In the six subsequent weeks, subjects were given increasing doses of MK-7 (10, 20 and 45 μg day-1) while continuing acenocoumarol treatment at established individual doses. Results: Apart from the INR, acenocoumarol treatment significantly increased the levels of uncarboxylated factor II (ucFII), uncarboxylated osteocalcin (ucOC), and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP), and decreased endogenous thrombin generation (ETP). A daily intake of 45 μg of MK-7 significantly decreased the group mean values of both the INR and ucFII by ~ 40%. Daily intakes of 10 and 20 μg of MK-7 were independently judged by two hematologists to cause a clinically relevant lowering of the INR in at least 40% and 60% of subjects, respectively, and to significantly increase ETP by ~ 20% and ~ 30%, respectively. Circulating ucOC and dp-ucMGP were not affected by MK-7 intake. Conclusions: MK-7 supplementation at doses as low as 10 μg (lower than the usual retail dose of 45 μg) significantly influenced anticoagulation sensitivity in some individuals. Hence, the use of MK-7 supplements needs to be avoided in patients receiving VKA therapy. © 2013 International Society on Thrombosis and Haemostasis.