Effect of low-dose supplements of menaquinone-7 (vitamin K-2) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers

E. Theuwissen*, K. J. Teunissen, H. M. H. Spronk, K. Hamulyak, H. Ten Cate, M. J. Shearer, C. Vermeer, L. J. Schurgers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background and ObjectiveDespite the worldwide use of vitaminK antagonists (VKAs), there is limited knowledge of the influence of dietary vitaminK on anticoagulation control. In view of the increasing nutraceutical availability of menaquinone-7 (MK-7; vitaminK(2)) 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. PatientsEighteen healthy men and women were anticoagulated for 4weeks 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 45gday(-1)) while continuing acenocoumarol treatment at established individual doses. ResultsApart from the INR, acenocoumarol treatment significantly increased the levels of uncarboxylated factorII (ucFII), uncarboxylated osteocalcin (ucOC), and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP), and decreased endogenous thrombin generation (ETP). A daily intake of 45g of MK-7 significantly decreased the group mean values of both the INR and ucFII by similar to 40%. Daily intakes of 10 and 20g 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 similar to 20% and similar to 30%, respectively. Circulating ucOC and dp-ucMGP were not affected by MK-7 intake. ConclusionsMK-7 supplementation at doses as low as 10g (lower than the usual retail dose of 45g) significantly influenced anticoagulation sensitivity in some individuals. Hence, the use of MK-7 supplements needs to be avoided in patients receiving VKA therapy.
Original languageEnglish
Pages (from-to)1085-1092
JournalJournal of Thrombosis and Haemostasis
Issue number6
Publication statusPublished - Jun 2013


  • International Normalized Ratio
  • matrix Gla-protein
  • menaquinone-7
  • oral anticoagulants
  • osteocalcin
  • thrombin generation

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