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Vitamin K for vascular health

How does vitamin K supplementation impact vascular calcification and stiffness? And does observational evidence suggest an association between vitamin K status and cardiovascular disease and death?

Study under review: Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis.

Introduction

Cardiovascular disease (CVD) is the number one cause of death globally[1], estimated to account for almost one-third of all deaths around the world. CVD consists of complications relating to the heart and blood flow[2] throughout the body, which includes strokes, heart attacks, atherosclerosis, and more.

While traditional markers for CVD[3] include cholesterol-related blood lipids, inflammatory markers, blood clotting factors, hormones, and lifestyle, vascular-related markers such as vascular calcification (VC)[4] and vascular stiffness (VS)[5] have begun to demonstrate strong associations with CVD and mortality. While there are no clear pharmacological treatments available to mediate vascular calcification and stiffness, recent studies[6] suggest vitamin K may offer a cheap and safe therapeutic intervention.

Vitamin K[7] is fat soluble and mainly known for its role in blood coagulation and required as a cofactor for various vitamin K-dependent proteins (VKDPs). As you can see in Figure 1, vitamin K is needed to carboxylate the VKDPs to activate them, meaning inactive uncarboxylated VKDPs (ucVKDPs) serve as indicators of vitamin K deficiency. One example is matrix GLA protein (MGP), which binds Ca2+ and inhibits VC. Another example is osteocalcin (OC)[8], which also binds Ca2+ and contributes to bone formation. Thus, vitamin K status may have an influence on VC[9] and osteoporosis[10] via these two proteins.

Some studies[6] have suggested there is evidence for a protective effect from vitamin K supplementation on VS and VC, while other studies[11][12] have reported no effect. It is not clear whether vitamin K supplementation can reduce VC or VS, nor whether ucVKDPs are associated with hard endpoints such as CVD or mortality. The authors of the two-part systematic review and meta-analysis under review aimed to clarify these concerns.

Vitamin K is a cofactor for various proteins that may have an impact on markers of vascular health that have recently demonstrated strong associations with CVD. Inconsistent results from trials of vitamin K supplementation’s impact on vascular calcification and stiffness, as well as a lack of knowledge on vitamin K-dependent proteins’ associations with CVD or mortality, drove the authors of the study under review to evaluate the available literature through a systematic review and meta-analysis.

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Other Articles in Issue #51 (January 2019)