Vitamin K2-a neglected player in cardiovascular health: a narrative review

Abstract

Vitamin K₂ serves an important role in cardiovascular health through regulation of calcium homeostasis. Its effects on the cardiovascular system are mediated through activation of the anti-calcific protein known as matrix Gla protein. In its inactive form, this protein is associated with various markers of cardiovascular disease including increased arterial stiffness, vascular and valvular calcification, insulin resistance and heart failure indices which ultimately increase cardiovascular mortality. Supplementation of vitamin K₂ has been strongly associated with improved cardiovascular outcomes through its modification of systemic calcification and arterial stiffness. Although its direct effects on delaying the progression of vascular and valvular calcification is currently the subject of multiple randomised clinical trials, prior reports suggest potential improved survival among cardiac patients with vitamin K₂ supplementation. Strengthened by its affordability and Food and Drug Adminstration (FDA)-proven safety, vitamin K₂ supplementation is a viable and promising option to improve cardiovascular outcomes.

Keywords: atherosclerosis; biomarkers; clinical; coronary vessels; heart valve diseases; pharmacology.

Figure 1

Mechanism of action of vitamin K₂. Vitamin K₂ is as a cofactor for gamma-carboxylation of dp-ucMGP into dp-cMGP in vascular smooth muscle cells and chondrocytes. dp-cMGP undergoes an additional phosphorylation by a casein kinase in Golgi bodies into p-cMGP, the final active form of MGP that ultimately inhibits soft tissue calcification. Inactive dp-ucMGP is a biomarker of poor vitamin K status in the circulation and is associated with increased deposition of calcium into blood vessels, predisposing to arterial stiffness via medial calcification and atherosclerosis via atheroma calcification. On the other hand, vitamin K-dependent carboxylation activates osteocalcin (OC), also known as bone Gla protein, and the latter not only promotes bone growth but also plays a role in preventing soft tissue calcification through inhibiting calcium and phosphate precipitation. dp-uc, dephospho-uncarboxylated; MGP, matrix Gla protein.

Figure 2

Role of vitamin K₂ on various measures of cardiovascular health. Based on a myriad of preclinical, epidemiological and interventional studies, vitamin K₂ has been shown to have strong potential in reducing several surrogate measures of cardiovascular morbidity and mortality, including arterial stiffness, valvular calcification, arterial calcification, cardiac systolic and diastolic functions. In light of such evidence, vitamin K₂ has been strongly associated with improved cardiovascular health by improving arterial, endothelial and myocardial function and with potential for improved overall survival.