Do vitamin K2 (menaquinone) and vitamin D3 (cholecalciferol) improve coagulation?

Vitamin K2 and D3 Effects on Coagulation

Vitamin K2 (menaquinone) supports normal coagulation by activating vitamin K-dependent clotting factors, but supplementation at recommended doses does not enhance coagulation beyond normal levels in healthy individuals. Vitamin D3 has no direct role in the coagulation cascade. 1, 2

Vitamin K2's Role in Coagulation

Mechanism of Action

• Vitamin K2 functions as an essential cofactor for the carboxylation of glutamic acid residues on coagulation factors II, VII, IX, and X, as well as anticoagulant proteins C and S. 1
• This carboxylation step is required to render these clotting factors biologically active and capable of binding to phospholipid surfaces during the coagulation cascade. 1, 3
• Vitamin K2 can bypass the warfarin-sensitive vitamin K epoxide reductase step, which is why it can overcome warfarin's anticoagulant effects. 1

Effect of K2 Supplementation in Healthy Individuals

• A 2021 study demonstrated that menaquinone-7 (MK-7) supplementation at 90 μg daily for 30 days did not alter prothrombin time (PT), activated partial thromboplastin time (APTT), or the activities of coagulation factors II, VII, IX, and X in healthy adults. 2
• PIVKA-II levels (undercarboxylated prothrombin, a marker of vitamin K deficiency) remained unchanged, indicating that supplementation does not enhance carboxylation beyond normal physiological levels in vitamin K-replete individuals. 2
• This means K2 supplementation corrects deficiency but does not create a hypercoagulable state in healthy people. 2

Clinical Context: Deficiency vs. Sufficiency

• Vitamin K deficiency leads to decreased functioning of vitamin K-dependent clotting factors, prolonged coagulation times, and bleeding tendency. 3
• Both vitamin K1 (phylloquinone) and K2 (menaquinones) contribute to maintaining adequate vitamin K status, with dietary menaquinones accounting for up to 25% of total vitamin K intake. 4
• Intestinal bacteria synthesize menaquinones (particularly in the ileum), which contribute significantly to vitamin K requirements, especially during periods of dietary insufficiency. 5

Important Caveats

• In patients taking vitamin K antagonists (warfarin), vitamin K2 supplementation can reduce anticoagulant effectiveness. Doses exceeding 150 μg can cause warfarin resistance by bypassing the drug's mechanism of action. 1, 6
• Vitamin K2 supplementation is safe and does not cause toxicity even at high doses in individuals not on anticoagulants. 6, 7
• Natural forms of vitamin K (K1 and K2) have no established upper safety limit and do not cause adverse effects. 6

Vitamin D3 and Coagulation

• Vitamin D3 (cholecalciferol) has no direct role in the coagulation cascade. The evidence provided does not support any mechanism by which vitamin D3 affects clotting factor synthesis or function.
• Vitamin D3 should not be confused with vitamin K; they are entirely separate vitamins with distinct biological functions.

Clinical Bottom Line

For patients with normal vitamin K status not on anticoagulants: K2 supplementation maintains normal coagulation but does not enhance it beyond physiological levels. 2

For patients on warfarin: Avoid K2 supplementation or maintain consistent intake, as it can interfere with anticoagulation control. 1, 6

For vitamin K-deficient patients: K2 supplementation will restore normal coagulation function by enabling proper carboxylation of clotting factors. 3, 5