title: Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: VitaK & Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. e.theuwissen@vitak.com
authors.forename: E
authors.initials: E
authors.lastname: Theuwissen
authors.forename: K J
authors.initials: KJ
authors.lastname: Teunissen
authors.forename: H M H
authors.initials: HM
authors.lastname: Spronk
authors.forename: K
authors.initials: K
authors.lastname: Hamulyák
authors.forename: H
authors.initials: H
authors.lastname: Ten Cate
authors.forename: M J
authors.initials: MJ
authors.lastname: Shearer
authors.forename: C
authors.initials: C
authors.lastname: Vermeer
authors.forename: L J
authors.initials: LJ
authors.lastname: Schurgers
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000886:Anthropometry; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006490:Hemostatics / Q000627:therapeutic use; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000737:chemistry; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D006490:Hemostatics; D024482:Vitamin K 2; C062629:menaquinone 7; D013917:Thrombin; D000074:Acenocoumarol
keywords: International Normalized Ratio; matrix Gla-protein; menaquinone-7; oral anticoagulants; osteocalcin; thrombin generation