Daily vitamin K supplementation improves anticoagulant stability

J Thromb Haemost. 2007 Oct;5(10):2043-8. doi: 10.1111/j.1538-7836.2007.02715.x. Epub 2007 Jul 31.


Background: One of the causes of unstable anticoagulant control in patients using vitamin K antagonists is a fluctuating intake of vitamin K. Research suggests that patients with a low dietary intake of vitamin K have a less stable anticoagulant control than patients with a higher intake.

Objectives: To study whether supplementation with a low daily dose of vitamin K improves anticoagulant control.

Methods: We performed a double-blind, randomized, placebo-controlled trial. 200 patients of the Leiden anticoagulation clinic, who used the vitamin K antagonist phenprocoumon, were randomized to receive either adjusted-dose phenprocoumon and 100 mug vitamin K once daily or adjusted-dose phenprocoumon and a placebo. Treatment duration was 24 weeks. The primary outcome was the percentage of time the International Normalized Ratio was within the therapeutic range.

Results: The time in the therapeutic range was 85.5% in the placebo group and 89.5% in the vitamin K group (adjusted difference 3.6%; 95% CI -0.8% to 8.0%). The time below the therapeutic range was 3.1% in the placebo group and 2.1% in the vitamin K group (adjusted difference -0.7%; 95% CI -2.5% to 1.1%) and the time above the therapeutic range was 11.4% in the placebo group and 8.5% in the vitamin K group (adjusted difference -2.9%; 95% CI -6.9% to 1.1%). The relative risk (RR) of a maximal stability in the vitamin K group compared to the placebo group was 1.8 (95%, CI 1.1-2.7).

Conclusion: Supplementation of vitamin K antagonists with 100 mug vitamin K improves stability of anticoagulant therapy. Because the risk of side effects is inversely related to anticoagulant stability, such an improvement is likely to reduce the number of bleeding and thrombotic events.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / pharmacology*
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Phenprocoumon / therapeutic use
  • Placebos
  • Risk
  • Treatment Outcome
  • Vitamin K / administration & dosage*
  • Vitamin K / antagonists & inhibitors


  • Anticoagulants
  • Placebos
  • Vitamin K
  • Phenprocoumon