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

J Thromb Haemost. 2013 Jun;11(6):1085-92. doi: 10.1111/jth.12203.


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.

Keywords: International Normalized Ratio; matrix Gla-protein; menaquinone-7; oral anticoagulants; osteocalcin; thrombin generation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acenocoumarol / administration & dosage
  • Administration, Oral
  • Adolescent
  • Adult
  • Anthropometry
  • Anticoagulants / administration & dosage*
  • Anticoagulants / therapeutic use*
  • Blood Coagulation / drug effects
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Healthy Volunteers
  • Hemostatics / therapeutic use
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Thrombin / chemistry
  • Vitamin K 2 / analogs & derivatives*
  • Vitamin K 2 / therapeutic use
  • Young Adult


  • Anticoagulants
  • Hemostatics
  • Vitamin K 2
  • menaquinone 7
  • Thrombin
  • Acenocoumarol