Vitamin K2 Does Interact with Warfarin
Both vitamin K1 and vitamin K2 can antagonize warfarin's anticoagulant effect, though they work through different mechanisms. Vitamin K2 can bypass the warfarin-sensitive vitamin K epoxide reductase step, directly overcoming warfarin's action, while vitamin K1 is the primary dietary form that requires consistent intake management 1.
Mechanism of Interaction
Vitamin K2 bypasses warfarin's primary site of action:
Warfarin works by inhibiting vitamin K epoxide reductase, which blocks the conversion of vitamin K epoxide back to vitamin K1, thereby preventing the formation of reduced vitamin K (KH2) needed for clotting factor activation 1
Vitamin K2, whether given therapeutically or derived from food sources, can overcome warfarin's effect by bypassing the warfarin-sensitive vitamin K epoxide reductase step in the formation of vitamin KH2 1
This means vitamin K2 can directly provide substrate for clotting factor carboxylation without needing the enzyme that warfarin blocks 1
Clinical Evidence for Vitamin K2 Interaction
Vitamin K2 administration demonstrably reduces INR in warfarin-treated patients:
In a population pharmacokinetic/pharmacodynamic analysis of 100 patients undergoing catheter ablation, vitamin K2 administration of more than 20 mg caused a dose-dependent decrease in INR and delayed INR elevation after warfarin re-initiation 2
The study successfully modeled the antagonistic effect of vitamin K2 on warfarin's anticoagulant activity, confirming the clinical significance of this interaction 2
Intestinal bacterial production of vitamin K2 may contribute to increased warfarin dose requirements in patients with small intestinal bacterial overgrowth, though the mechanism appears complex and may involve enhanced vitamin K1 absorption rather than solely increased K2 biosynthesis 3
Practical Implications
Both forms of vitamin K require clinical attention in warfarin management:
Dietary vitamin K1 from green vegetables and plant oils remains the primary concern for day-to-day INR stability, as fluctuating intake is the most common cause of anticoagulation variability 1, 4
Therapeutic vitamin K2 (typically given as 10-20 mg intravenously in Japan for urgent warfarin reversal) will antagonize warfarin, though doses above 20 mg should be avoided as they cause excessive INR reduction and delayed re-anticoagulation 2
Maintaining consistent vitamin K intake (both K1 and K2 sources) at approximately 65-80 micrograms/day supports stable anticoagulation 4
Common Pitfalls
Do not assume only vitamin K1 matters clinically:
While vitamin K1 is emphasized in dietary counseling, vitamin K2 from fermented foods (natto, certain cheeses) and supplements can also affect INR 3
Therapeutic vitamin K2 administration requires the same caution as vitamin K1 regarding warfarin resistance and overcorrection 2
Patients taking vitamin K2 supplements for bone health should be counseled that these will interact with warfarin, requiring INR monitoring and potential warfarin dose adjustment 2