Functions of Vitamin K2
Vitamin K2 (menaquinone) plays crucial roles in blood coagulation, bone metabolism, and cardiovascular health by activating vitamin K-dependent proteins through carboxylation of glutamic acid residues. 1
Primary Functions of Vitamin K2
Blood Coagulation
- 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
- Enables these coagulation factors to bind calcium, which is necessary for their biological activity 1
- Deficiency can lead to bleeding disorders due to impaired clotting function 1
Bone Health
- Activates osteocalcin, the major non-collagenous protein in bone matrix, through carboxylation 2, 3
- Regulates bone-specific gene expression through the steroid and xenobiotic receptor (SXR) 2
- Increases expression of bone markers including bone alkaline phosphatase, osteoprotegerin, osteopontin, and matrix Gla protein 2
- Low vitamin K2 intake is associated with increased bone loss and fracture risk 3, 4
- Works synergistically with calcium and vitamin D to maintain bone density and strength 3
Cardiovascular Health
- Activates matrix Gla protein (MGP), which inhibits calcium deposition in arterial walls 5
- Prevents arterial calcification and arterial stiffening 5
- May reduce the risk of vascular damage by promoting calcium removal from blood vessels 5
Clinical Implications
Deficiency Risks
- Vitamin K2 deficiency can contribute to:
- Bleeding disorders
- Poor bone development
- Osteoporosis
- Increased cardiovascular disease risk 1
- In normal healthy adults, 8-31% have vitamin K deficiency based on undercarboxylated protein analysis 1
Supplementation Considerations
- Unlike vitamin K1, there are no established adequate intake (AI) recommendations specifically for vitamin K2 due to lack of data 1, 6
- Vitamin K2 is not associated with toxicity, unlike synthetic vitamin K3 1
- Vitamin K2 supplementation may be beneficial for:
Monitoring and Assessment
- Vitamin K status should be measured in at-risk patients, including those with:
- Conditions causing steatorrhea
- Prolonged use of broad-spectrum antibiotics
- Chronic kidney disease 1
- Assessment requires a combination of biomarkers and dietary intake evaluation 1
- PIVKA-II (protein induced by vitamin K absence or antagonism-II) is a sensitive biomarker for hepatic subclinical vitamin K deficiency 1, 7
Important Clinical Considerations
- Vitamin K2 has different pharmacokinetics and bioavailability compared to vitamin K1 6
- Vitamin K2 may be more effective in activating extra-hepatic vitamin K-dependent proteins than vitamin K1 6
- Vitamin K2 can overcome the effect of warfarin by bypassing the warfarin-sensitive vitamin K oxide reductase step 1
- Patients on warfarin should maintain consistent vitamin K intake to avoid fluctuations in anticoagulation control 1
- Dietary sources of vitamin K2 are limited in Western diets, with higher amounts found in fermented foods and animal products 5, 6
Understanding the multifaceted functions of vitamin K2 is essential for optimizing bone and cardiovascular health, especially in populations at risk for deficiency or those with conditions affecting vitamin K metabolism.