What is Vitamin K2?

Vitamin K2: Functions, Benefits, and Clinical Implications

Vitamin K2, also known as menaquinone (MK), is a fat-soluble vitamin that plays crucial roles in bone metabolism, cardiovascular health, and blood clotting, with emerging evidence supporting its importance for reducing morbidity and mortality related to osteoporosis and cardiovascular disease. 1

What is Vitamin K2?

• Vitamin K2 belongs to a group of fat-soluble compounds with the chemical formulation MK (menaquinone), ranging from MK-2 to MK-14 2
• Unlike vitamin K1 (phylloquinone) which is primarily found in leafy greens and plant sources, vitamin K2 is primarily produced by gram-negative bacteria in the human gastrointestinal tract 3
• Currently, there is insufficient data to establish an Adequate Intake (AI) for vitamin K2, while vitamin K1 has established recommendations (120 μg for adult males and 90 μg for adult females) 4

Physiological Functions of Vitamin K2

• Vitamin K2 is essential for the carboxylation of vitamin K-dependent proteins, including those involved in bone formation and preventing vascular calcification 1
• It contributes to the structural integrity of osteocalcin, the major non-collagenous protein found in bone matrix 2
• Vitamin K2 acts as a transcriptional regulator of bone-specific genes through the steroid and xenobiotic receptor (SXR), promoting the expression of osteoblastic markers 5
• It helps prevent the "calcium paradox" phenomenon, characterized by low calcium deposition in bone and accumulation in vessel walls 6

Clinical Implications

Bone Health

• Low vitamin K2 intake is linked to bone loss and increased fracture risk in both men and women 2
• Vitamin K2 supplementation enhances the effectiveness of calcium and vitamin D for bone health 2
• Level I and II evidence supports the use of vitamin K2 in osteoporosis management, potentially rivaling bisphosphonate therapy without the associated toxicity 1

Cardiovascular Health

• Level II evidence supports vitamin K2 in preventing coronary calcification and cardiovascular disease 1
• Vitamin K2 deficiency contributes to vascular calcification, a significant risk factor for cardiovascular morbidity and mortality 6
• It may significantly reduce cardiovascular events by preventing calcium deposition in arterial walls 1

Other Potential Benefits

• Emerging research suggests possible benefits in diabetes, cancer, and osteoarthritis, though evidence remains insufficient for definitive recommendations 1
• Vitamin K2 has been associated with lower concentrations of inflammatory markers and may exert anti-inflammatory effects by suppressing NF-kB signal transduction 4

Safety and Interactions

• Unlike synthetic vitamin K3 (which is toxic), vitamin K1 and K2 are not associated with toxicity 4
• Patients using anti-vitamin K drugs (warfarin) should be monitored with blood clotting tests and avoid making major sudden changes in vitamin K intake 4
• Vitamin K2 may be used as a supplementary agent for patients on warfarin therapy to improve INR control, though dosage adjustments would be required 1

Clinical Recommendations

• Vitamin K2 supplementation should be considered for patients at risk of osteoporosis and cardiovascular disease due to its dual beneficial effects on bone formation and prevention of vascular calcification. 1, 6
• Vitamin K status should be assessed in patients with risk factors for deficiency, including conditions causing steatorrhea, prolonged use of broad-spectrum antibiotics, and chronic kidney disease 4
• When prescribed as a supplement, menaquinone-7 (a form of vitamin K2) is typically administered at a dosage of 4 capsules once daily or as prescribed by a licensed medical practitioner 7

Monitoring and Assessment

• No single biomarker is established to determine vitamin K status; a combination of biomarkers along with dietary intake assessment is recommended 4
• Measurement of undercarboxylated proteins (such as PIVKA-II) can serve as sensitive markers of subclinical vitamin K deficiency 4
• Special preanalytical, analytical, and storage conditions must be applied to prevent vitamin K degradation by light exposure, alkaline conditions, and temperature 4