The effect of dietary vitamin K on warfarin‐induced anticoagulation

Abstract

We examined the effect of vitamin-K-rich vegetables, vitamin-K-poor vegetables and phytomenadione on the stability of warfarin-induced anticoagulation. Patients on stable anticoagulant treatment were randomized to either 1 (n = 5), 2 (n = 7) or 7 (n = 13) d with high intake of vitamin-K-rich vegetables (median daily vitamin K intake 1100 micrograms) or high intake of vitamin-K-poor vegetables (daily vitamin K intake 135 micrograms) for 6 d (n = 7), or habitual diet supplemented with 1000 micrograms of phytomenadione daily (n = 5). Nine patients (69%; 95% CI, 39-91%) who consumed vitamin-K-rich vegetables for 7 d reached activities above the therapeutic level. Two (40%; 95% CI, 5-85%) and three patients (43%; 95% CI, 10-86%) who consumed vitamin-K-rich vegetables for 1 and 2 d, respectively, exceeded the upper therapeutic limit. No changes were observed in the vitamin-K-poor group. All patients who received phytomenadione exceeded the upper therapeutic limit. Dietary vitamin K should be regarded as an important environmental factor contributing to unwanted disturbances in warfarin-induced anticoagulation.

Vitamin K deficiency amplifies anticoagulation response to ximelagatran: possible implications for direct thrombin inhibitors and their clinical safety

“…However, since the activation of thrombin is inextricably linked with the vitamin K cycle in the coagulation cascade, there is the possibility that the pharmacological activity of direct thrombin inhibitors could be influenced by alterations in vitamin K availability. The enhanced pharmacological activity of warfarin in vitamin K deficient rats observed in this study confirms the well-established impact of vitamin K deficiency on anticoagulation response to warfarin in man [4][5][6][8][9][10]. This study also demonstrates that overt vitamin K deficiency enhances the anticoagulant activity of the direct thrombin inhibitor, ximelagatran, in rats.…”

“…Warfarin causes anticoagulation by inhibiting the reductase enzymes, which generate vitamin K hydroquinone from vitamin K epoxide in the liver, thus preventing activation of the clotting proteins [7]. The availability of vitamin K thus plays a role in determining the effectiveness of warfarin, and dietary modification by either lowering or increasing vitamin K intake can increase or decrease patients' sensitivities to the drug [5,[8][9][10].…”

Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin

“…Alterations in dietary intake of vitamin K can have a significant effect on anticoagulation response to oral anticoagulants; increases in the dietary intake of vitamin K are associated with significant reductions in anticoagulation response, 6,9,[12][13][14][15] whereas the opposite causes warfarin sensitivity. 6,12 Earlier we showed that in patients with stable control of anticoagulation, for every 100-g increase in vitamin K intake in the previous 4 days, INR falls by 0.2, 16 further exemplifying the relationships between dietary vitamin K and anticoagulation response.…”

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

“…12 Current information comes from sporadic case reports, mostly documenting a resistance to OACs from increased intakes of vitamin K-rich foods 13,14 or supplements 15,16 or from limited experimental studies in patients. 17,18 Here, we report a systematic vitamin K dose-response study in 12 young healthy adults who had been initially stabilized with acenocoumarol for 4 weeks to a target INR of 2.0. Although this target INR is at the low end of the target ranges for most short-term (full-dose) OAC regimens, it is at the upper end of the target INR of 1.5 to 2.0 used in the recent, and highly successful, long-term trial using low-intensity warfarin to prevent recurrent venous thromboembolism.…”