Role of dietary vitamin K intake in chronic oral anticoagulation: prospective evidence from observational and randomized protocols

Am J Med. 2004 May 15;116(10):651-6. doi: 10.1016/j.amjmed.2003.12.036.


Purpose: The potential association between vitamin K intake and coagulation instability has been explored primarily in case reports and small, retrospective, uncontrolled studies. We prospectively evaluated the effects of dietary vitamin K intake on anticoagulation parameters.

Methods: In an observational protocol, clinical characteristics and vitamin K intake, assessed semiquantitatively, were evaluated in 39 outpatients who made 230 visits to our anticoagulation clinic. In a randomized crossover protocol, 12 patients with stable anticoagulation underwent 4-day in-hospital dietary interventions, 1 to 2 weeks apart, providing a 500% increase and an 80% decrease in vitamin K intake relative to the baseline level.

Results: Univariate analysis of the observational data demonstrated a progressive, statistically significant inverse association between the vitamin K intake score and different levels of anticoagulation. Multivariate logistic regression analysis showed that vitamin K intake was independently associated with both overcoagulation and undercoagulation. In the randomized protocol, the international normalized ratio increased from 2.6 +/- 0.5 at baseline to 3.3 +/- 0.9 at day 7 (P = 0.005) in subjects on the vitamin K-depleted diet and decreased from 3.1 +/- 0.8 at baseline to 2.8 +/- 0.6 at day 4 (P = 0.04) in those on the vitamin K-enriched diet.

Conclusion: Our prospective data strengthen the concept that the interaction between vitamin K and coumarin is a clinically relevant, major independent factor that interferes with anticoagulation stability.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anticoagulants / pharmacology*
  • Blood Coagulation / drug effects*
  • Case-Control Studies
  • Cross-Over Studies
  • Diet*
  • Drug Monitoring
  • Female
  • Food-Drug Interactions*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Observation
  • Phenprocoumon / pharmacology
  • Prospective Studies
  • Vitamin K / pharmacology*
  • Warfarin / pharmacology


  • Anticoagulants
  • Vitamin K
  • Warfarin
  • Phenprocoumon