Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients. A prospective, controlled trial

Daniel Kurnik, Ronen Loebstein, Hadas Rabinovitz, Naomi Austerweil, Hillel Halkin*, Shlomo Almog

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Most multivitamin supplements contain far less vitamin K1 than thought to affect warfarin anticoagulation. Having described 3 patients with multivitamin-warfarin interactions, we hypothesized that vitamin K1-depleted patients are sensitive to even small increments. Therefore, we compared the effect of a vitamin K1-containing multivitamin on warfarin anticoagulation between patients with low versus normal vitamin K1 status. We screened 102 warfarin-treated patients and recruited nine with "low" (< 1.5 mcg/L, 10th percentile) (group 1) and 7 with "normal" (>4.5 mcg/L, median) (group 2) total vitamin K1 plasma levels (vitamin K1 + vitamin K1 2,3-epoxide). Patients received one multivitamin tablet containing 25 mcg of vitamin K1 daily, for 4 weeks (period 1). A predefined algorithm was used to adjust warfarin doses if the INR was outside the therapeutic range. Patients requiring warfarin increments were then switched to 4 weeks of a vitamin K1-free multivitamin supplement (period 2). During period 1, subtherapeutic INRs occurred in 9/9 and 1/7 patients in group 1 and 2, respectively (p <0.001). In group 1, INR decreased by a median of 0.51 (p <0.01), and warfarin dose had to be raised by 5.3% (p <0.01), whereas INR and warfarin dose did not change significantly in group 2. During period 2 (7 patients), there were trends towards decreased total vitamin K1 and rising INRs associated with significantly lower warfarin doses. We conclude that vitamin K1-containing multivitamins reduce INR in patients with low vitamin K1 status. Our study suggests that vitamin K-depleted patients are sensitive to even small changes in vitamin K1 intake.

Original languageEnglish
Pages (from-to)1018-1024
Number of pages7
JournalThrombosis and Haemostasis
Volume92
Issue number5
DOIs
StatePublished - Nov 2004

Keywords

  • Clinical trials
  • Clinical/epidemiological studies
  • Oral anticoagulants
  • Vitamin K-dependent factors

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