What are the guidelines for Vitamin K1 (phylloquinone) and K2 (menaquinone) supplementation, particularly in relation to anticoagulant medications like warfarin (coumarin)?

Guidelines for Vitamin K1 and K2 Supplementation in Relation to Anticoagulant Medications

Patients receiving warfarin should not take vitamin K supplements (either K1 or K2) due to the direct antagonistic effect on anticoagulation therapy. 1

Mechanism of Interaction Between Vitamin K and Warfarin

Warfarin works by inhibiting the C1 subunit of vitamin K epoxide reductase (VKORC1) enzyme complex, which reduces the regeneration of vitamin K1 epoxide 2. This inhibition leads to:

• Decreased synthesis of vitamin K-dependent clotting factors (II, VII, IX, X)
• Reduced activity of anticoagulant proteins C and S
• Overall anticoagulant effect measured by INR (International Normalized Ratio)

Vitamin K (both K1 and K2) directly counteracts warfarin's mechanism of action by bypassing the warfarin-sensitive step in the formation of vitamin KH2, which is essential for blood clotting 1.

Clinical Recommendations for Patients on Warfarin

1. Avoid vitamin K supplements:

   • Both K1 (phylloquinone) and K2 (menaquinone) supplements should be avoided by patients on warfarin 1
   • Even multivitamins containing small amounts (25 μg) of vitamin K can affect anticoagulation in susceptible patients 3

2. Maintain consistent dietary vitamin K intake:

   • Rather than restricting vitamin K-rich foods, patients should maintain stable dietary habits 4
   • Wide fluctuations in vitamin K intake can destabilize anticoagulation control
   • Excessive consumption of vitamin K-rich foods (broccoli, spinach) over consecutive days may reduce warfarin effectiveness 5

3. Monitor for vitamin K deficiency:

   • About 12% of anticoagulated patients may have very low vitamin K levels (<0.1 ng/mL) 3
   • These patients may be particularly sensitive to even small changes in vitamin K intake

Managing Warfarin Overanticoagulation with Vitamin K

When INR is excessively elevated due to warfarin, vitamin K1 (not K2) should be administered according to the following protocol 1:

1. INR above therapeutic range but <5 without bleeding:

   • Reduce or omit next warfarin dose
   • Resume at lower dose when INR approaches desired range

2. INR 5-9 without bleeding:

   • Omit 1-2 doses of warfarin and reinstate at lower dose when INR normalizes
   • For patients at increased bleeding risk: omit next dose and give vitamin K1 1-2.5 mg orally

3. INR >9 without significant bleeding:

   • Give vitamin K1 3-5 mg orally
   • Monitor INR closely and repeat vitamin K as necessary

4. Serious bleeding or major overdose (INR ≥20):

   • Give vitamin K1 10 mg by slow IV infusion
   • Supplement with fresh plasma or prothrombin complex concentrate
   • Additional doses of vitamin K1 may be needed every 12 hours

Special Considerations

• Enteral nutrition: Should be withheld 1 hour before and after anticoagulant administration to prevent interactions 1

• Parenteral nutrition: Vitamin K content from lipid emulsions (6-300 μg/100g) should be included in requirement calculations 1

• Vitamin K1 vs K2: Clinical guidelines specifically recommend vitamin K1 for reversal of warfarin effects, although K2 has been used in some countries like Japan 6

• Route of administration: Oral administration of vitamin K is preferred over intravenous (risk of anaphylactoid reactions) or subcutaneous (risk of cutaneous reactions) routes 7

Pitfalls to Avoid

1. Overcorrection: High doses of vitamin K can lead to warfarin resistance for up to a week 1

2. Inconsistent dietary advice: Restricting vitamin K-rich foods is not supported by evidence; maintaining stable intake is more important 4

3. Overlooking multivitamins: Even low-dose vitamin K in multivitamins can affect anticoagulation in susceptible patients 3

4. Ignoring individual variability: Patients with low baseline vitamin K status may be more sensitive to small changes in vitamin K intake 3