What is the role of vitamin K2 in the body?

Vitamin K2: Role in the Body

Vitamin K2 functions primarily in blood clotting through carboxylation of clotting factors, and plays critical roles in bone mineralization, cardiovascular health by preventing vascular calcification, and anti-inflammatory processes. 1

Primary Biological Functions

Blood Coagulation

• Vitamin K2 is essential for the carboxylation of vitamin K-dependent clotting factors (II, VII, IX, X), enabling proper blood coagulation 1
• Without adequate vitamin K2, these clotting factors remain undercarboxylated and biologically inactive, leading to prolonged prothrombin time and bleeding risk 1

Bone Health and Mineralization

• Vitamin K2 carboxylates osteocalcin, the major non-collagenous protein in bone matrix, which is critical for calcium binding and bone structural integrity 2, 3
• Vitamin K2 acts as a transcriptional regulator through the steroid and xenobiotic receptor (SXR), upregulating osteoblast markers including bone alkaline phosphatase, osteoprotegerin, osteopontin, and matrix Gla protein 4
• Vitamin K2 increases bone-building processes while decreasing bone-loss processes, making it effective for osteoporosis prevention and treatment 5, 6
• Low vitamin K2 intake is linked to increased fracture risk in both sexes 2

Cardiovascular Protection

• Vitamin K2 prevents vascular calcification by carboxylating matrix Gla protein (MGP), which inhibits calcium deposition in arterial walls 1
• Vitamin K deficiency contributes to increased cardiovascular disease risk 1
• Level II evidence supports vitamin K2 in prevention of coronary calcification and cardiovascular disease 5

Anti-Inflammatory Effects

• Vitamin K2 suppresses NF-κB signal transduction, resulting in lower concentrations of inflammatory markers in vivo 1

Clinical Implications of Deficiency

Consequences

• Vitamin K deficiency causes significant bleeding, poor bone development, osteoporosis, and increased cardiovascular disease 1
• Clinically significant bleeding is most commonly reported in newborns and cases of extreme inadequate intake or malabsorption syndromes 1
• 8-31% of normal healthy adults have vitamin K deficiency based on undercarboxylated protein analysis 1

High-Risk Populations

• Conditions with fat malabsorption (celiac disease, cystic fibrosis, short bowel syndrome) 1
• Malnutrition states 1
• Prolonged antibiotic therapy (disrupts intestinal vitamin K2 production) 1
• Warfarin/anticoagulant treatment 1
• Chronic cholestasis and chronic liver disease 7

Safety Profile

• Vitamin K1 and vitamin K2 are not associated with toxicity 1
• Vitamin K2 as menaquinone-7 (MK-7) has a documented history of safe and effective use, making it ideal for supplementation in pregnant women, nursing mothers, and children 3
• The lack of adverse effects contrasts sharply with synthetic vitamin K3, which is highly toxic and no longer available 1

Important Clinical Caveats

Anticoagulant Interactions

• Patients on anti-vitamin K drugs (warfarin) must avoid sudden major changes in vitamin K intake, as this affects anticoagulation control 1
• Through dose titration and patient counseling, stable anticoagulation is achievable if vitamin K intake is known and consistent 1
• Blood clotting tests should monitor patients using anti-vitamin K drugs 1

Measurement Limitations

• Current adequate intake (AI) recommendations are for vitamin K1 only due to lack of data for vitamin K2 1
• No single biomarker is established to determine vitamin K status; combination of biomarkers with dietary intake is required 1
• PIVKA-II (undercarboxylated prothrombin) is the most sensitive and specific marker for subclinical vitamin K deficiency 1, 7