What is Vitamin K2?
Vitamin K2, also known as menaquinone (MK), is a fat-soluble vitamin that is endogenously synthesized by intestinal bacteria and exists in several subtypes (MK-2 to MK-14) that differ in side chain length, with menaquinone-7 (MK-7) being particularly bioavailable and clinically relevant. 1, 2
Forms and Sources
Vitamin K exists in multiple forms with distinct characteristics:
- Vitamin K1 (phylloquinone) is the predominant dietary form found in plants, green leafy vegetables, cruciferous vegetables, asparagus, prunes, peas, and parsley 3, 1
- Vitamin K2 (menaquinone) is produced by intestinal bacteria and includes various subtypes (MK-2 through MK-14) that differ in their side chain length 1, 2
- Vitamin K2-7 (MK-7) is absorbed more readily than K1 and demonstrates superior bioavailability 2
Biological Functions
Blood Clotting
- Vitamin K2 serves as an essential cofactor for gamma-carboxylation of vitamin K-dependent clotting factors (II, VII, IX, X), which is critical for normal blood coagulation 4, 5
Bone Health
- K2 acts as a cofactor to convert undercarboxylated osteocalcin (ucOC) to its carboxylated form (cOC), facilitating calcium deposition in bones 2
- It upregulates osteoprotegerin, which acts as a decoy receptor for RANK ligand (RANKL), thereby inhibiting bone resorption 2
- K2 promotes the transition of osteoblasts to osteocytes and limits osteoclastogenesis 1
- Vitamin K2 has been approved for osteoporosis treatment in Japan since 1995, with evidence showing reduced fracture incidence and maintained bone mineral density 6
Cardiovascular Health
- K2 converts undercarboxylated matrix Gla protein (ucMGP) to its carboxylated form (cMGP), preventing vascular calcification 2
Additional Roles
- Anti-inflammatory effects through suppression of proinflammatory mediators (IL-1α, IL-1β, TNF-α) and NF-κB signal transduction 3, 2
- Transcriptional regulation through the steroid and xenobiotic receptor (SXR), inducing expression of bone markers including alkaline phosphatase, osteoprotegerin, osteopontin, and matrix Gla protein 5
- Potential benefits in diabetes, peripheral neuropathy, Alzheimer's disease, and cancer through various signal transduction pathways (PI3K/AKT, MAP Kinase, JAK/STAT) 2
Clinical Considerations
Deficiency
- Common causes include fat malabsorption syndromes (celiac disease, cystic fibrosis, short bowel), malnutrition, prolonged antibiotic use, anticoagulant therapy (warfarin), and chronic cholestasis 3, 4
- Deficiency contributes to bleeding disorders, poor bone development, osteoporosis, and increased cardiovascular disease risk 3
- 8-31% of normal healthy adults have vitamin K deficiency based on undercarboxylated protein analysis 3
Toxicity
- Vitamin K1 and K2 are not associated with toxicity, with no known adverse effects from supplementation 3
- Rare anaphylactoid reactions (bronchospasm, cardiac arrest) have been reported only with IV vitamin K1 administration 3
Dosing
- Current adequate intake recommendations are based on K1 only due to lack of data for K2: 1 mg/kg body weight per day (EFSA) or 120 mg for males and 90 mg for females (IOM) 3
- For K2-7 supplementation, the usual adult dose is 4 capsules once daily as prescribed 7
- In cystic fibrosis, vitamin K1 supplementation ranges from 0.3-1 mg/day for infants to 1-10 mg/day for older children and adults 3