Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects

Blood. 2004 Nov 1;104(9):2682-9. doi: 10.1182/blood-2004-04-1525. Epub 2004 Jul 1.


Oral anticoagulants exert their effect by blocking the utilization of vitamin K, yet little is known about competitive aspects of their interaction with dietary vitamin K. We carried out systematic dose-response studies in healthy volunteers who had been stably anticoagulated and maintained on their individualized doses for 13 weeks. First, we studied the response to weekly incremental doses (50 microg-500 microg) of vitamin K(1) supplements (K(1)) taken daily for 7 days. The threshold K(1) dose causing a statistically significant lowering of the INR was 150 microg/day. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 microg/day. Circulating undercarboxylated osteocalcin did not decrease until 300 microg K(1)/day compared with 100 microg K(1)/day for undercarboxylated FII, suggesting differential antidotal effects on bone and hepatic gamma-carboxylation. Next, we tested the response to vitamin K-rich food items. The short-lived response after meals of spinach and broccoli suggested an inefficient bioavailability from these 2 sources. We conclude that short-term variability in intake of K(1) is less important to fluctuations in the international normalized ratio (INR) than has been commonly assumed and that food supplements providing 100 microg/day of vitamin K(1) do not significantly interfere with oral anticoagulant therapy.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticoagulants / administration & dosage
  • Anticoagulants / therapeutic use*
  • Biological Availability
  • Brassica
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Drug Antagonism
  • Drug Stability
  • Female
  • Humans
  • International Normalized Ratio
  • Male
  • Osteocalcin / blood
  • Prothrombin / analysis
  • Spinacia oleracea
  • Vitamin K / administration & dosage
  • Vitamin K / pharmacology*


  • Anticoagulants
  • Osteocalcin
  • Vitamin K
  • Prothrombin