Vitamin K2 and Risk of Thrombosis
Vitamin K2 supplementation at recommended dosages does not increase the risk of thrombosis in healthy individuals without anticoagulation therapy. 1
Mechanism of Action and Normal Physiology
Vitamin K is a critical cofactor in the blood clotting cascade that enables the activation of several coagulation factors. It functions as a cofactor in the carboxylation of glutamic acid residues, allowing coagulation factors II, VII, IX, and X to bind to phospholipid surfaces and participate in blood coagulation. 2
Key points about vitamin K and coagulation:
- Vitamin K exists naturally in two forms:
- Phylloquinone (K1) found in plants
- Menaquinone (K2) produced by gut bacteria and available as supplements
- It serves as a cofactor for the carboxylation of glutamic acid residues to gamma-carboxyglutamic acid (Gla), essential for the biological activity of vitamin K-dependent proteins 2
Evidence on Vitamin K2 and Thrombosis Risk
The most recent and highest quality evidence comes from a 2021 study that specifically examined whether vitamin K2 (menaquinone-7) supplementation affects coagulation factors in healthy individuals:
- MK-7 supplementation at 90 μg for 30 days did not affect:
- Prothrombin time (PT)
- Activated partial thromboplastin time (APTT)
- Thrombin time (TT)
- Activities of coagulation factors II, VII, IX, and X
- PIVKA-II levels (Protein Induced by Vitamin K Absence or Antagonist-II) 1
This demonstrates that vitamin K2 supplementation at recommended dosages does not enhance coagulation activity or alter hemostatic balance in healthy individuals.
Special Considerations for Patients on Anticoagulants
For patients taking vitamin K antagonists (VKAs) like warfarin, vitamin K2 supplementation requires special consideration:
- High doses of vitamin K2 can reduce the anticoagulant effect of warfarin by promoting synthesis of active coagulation factors 3
- Guidelines recommend against routine use of vitamin K supplementation for patients with stable INRs who are taking VKAs (Grade 2C recommendation) 2
Vitamin K for Reversing Excessive Anticoagulation
In cases of excessive anticoagulation with VKAs:
- For patients with INR between 4.5 and 10 without bleeding, guidelines suggest against routine use of vitamin K (Grade 2B recommendation) 4
- For patients with mechanical valves and uncontrollable bleeding requiring immediate reversal of anticoagulation, administration of 4-factor prothrombin complex concentrate is reasonable 4
- For patients with mechanical valves and uncontrollable bleeding who have received prothrombin concentrate complex, adjunctive use of intravenous vitamin K is reasonable if resumption of VKA therapy is not anticipated for 7 days 4
Potential Benefits of Low-Dose Vitamin K Supplementation
Some studies suggest that low-dose vitamin K supplementation might improve anticoagulation control in patients on VKAs who may be vitamin K deficient, though results have not consistently reached statistical significance 5.
Clinical Implications
- For healthy individuals: Vitamin K2 supplementation at recommended dosages does not increase thrombosis risk
- For patients on warfarin: Vitamin K2 supplementation may interfere with anticoagulation and should be avoided or carefully monitored
- For patients with excessive anticoagulation: Vitamin K administration should follow established guidelines based on INR levels and bleeding status
Pitfalls to Avoid
- Assuming vitamin K2 supplementation increases thrombosis risk in all individuals
- Using high-dose vitamin K in patients on VKAs without appropriate indication
- Failing to monitor INR closely when vitamin K is administered to patients on VKAs
- Overlooking that vitamin K's effect on coagulation depends on dosage and the patient's anticoagulation status
In conclusion, while vitamin K2 plays an essential role in the coagulation cascade, supplementation at recommended dosages does not increase thrombosis risk in healthy individuals not taking anticoagulants.