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

Authors
  • Theuwissen, E1
  • Teunissen, K J
  • Spronk, H M H
  • Hamulyák, K
  • Ten Cate, H
  • Shearer, M J
  • Vermeer, C
  • Schurgers, L J
  • 1 VitaK & Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. [email protected] , (Netherlands)
Type
Published Article
Journal
Journal of thrombosis and haemostasis : JTH
Publication Date
Jun 01, 2013
Volume
11
Issue
6
Pages
1085–1092
Identifiers
DOI: 10.1111/jth.12203
PMID: 23530987
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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. 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.

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