Vitamin K2 Effects on the Body
Vitamin K2 primarily functions to activate proteins involved in blood clotting and calcium metabolism, with established roles in coagulation and emerging evidence for bone and cardiovascular health, though its clinical benefits beyond coagulation remain incompletely proven.
Primary Biological Mechanisms
Vitamin K2 carboxylates coagulation factors II, VII, IX, and X, making them functionally active and essential for normal blood clotting 1
Vitamin K2 serves as a cofactor for γ-glutamyl carboxylase, which activates various vitamin K-dependent proteins throughout the body by carboxylating glutamic acid residues 2
The compound demonstrates anti-inflammatory effects through suppression of NF-κB signal transduction, correlating with lower inflammatory marker concentrations 1
Effects on Bone Health
Vitamin K2 contributes to structural integrity of osteocalcin, the major non-collagenous protein in bone matrix, through carboxylation 3
The mechanism involves stimulating bone formation by promoting osteoblast differentiation and increasing alkaline phosphatase, insulin-like growth factor-1, growth differentiation factor-15, and stanniocalcin 2 levels 4
Vitamin K2 reduces bone resorption by decreasing osteoclast differentiation through increasing osteoprotegerin and reducing receptor activator of nuclear factor kappa-B ligand 4
It reduces pro-apoptotic proteins Fas and Bax in osteoblasts, protecting bone-building cells from death 4
However, the clinical evidence for bone benefits remains mixed—while observational studies link low vitamin K2 intake to increased fracture risk, large-scale randomized controlled trials have not consistently confirmed protective effects against osteoporosis 3, 5
Cardiovascular Effects
Vitamin K2 activates matrix Gla protein (MGP), the most potent inhibitor of cardiovascular calcifications, by carboxylating this protein 2
The mechanism reduces hydroxyapatite formation in blood vessels through carboxylation of MGP and Gla-rich protein 4
Vitamin K2 inhibits apoptosis of vascular smooth muscle cells by increasing growth arrest-specific gene 6, and reduces transdifferentiation of these cells to osteoblasts 4
Critical limitation: Despite compelling mechanistic data and observational studies linking vitamin K deficiency to cardiovascular calcification and mortality, multiple randomized controlled trials with high-dose menaquinone-7 (MK-7) supplements in patients with advanced chronic kidney disease have failed to confirm cardiovascular benefits 2
Safety Profile and Dosing
Vitamin K1 and K2 are not associated with toxicity, and MK-7 has a documented history of safe and effective use without adverse effects 1
The commonly used dosage in human studies is 45 mg/day, though no established adequate intake exists specifically for vitamin K2 (only for vitamin K1) 4, 1
Dietary sources include fermented cheeses, full-fat dairy products, and fermented dairy 1
Critical Clinical Caveat
Patients on warfarin or other anti-vitamin K drugs must maintain consistent vitamin K intake and avoid sudden major changes, as vitamin K2 can overcome warfarin's effect—blood clotting tests require monitoring in these patients 1
Practical Clinical Context
Vitamin K2 deficiency is particularly prevalent in patients with advanced chronic kidney disease, partly due to dietary restrictions and possibly impaired endogenous recycling 2
Subclinical non-hemostatic vitamin K deficiency in extrahepatic tissues (particularly bone and vasculature) exists widely in otherwise healthy adults 5
The evidence supports vitamin K2 supplementation as potentially beneficial for enhancing calcium and vitamin D therapy for bone health, but not as a standalone intervention with proven mortality or morbidity benefits 3