Evidence before enthusiasm: A critical review of the potential cardiovascular benefits of vitamin K

Authors: SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BERKNER, KATHLEEN - Cleveland Clinic; FERLAND, GUYLAINE - University Of Montreal; FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HOLDEN, RACHEL - Queen'S University - Canada; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Advances in Nutrition
Publication Type: Review Article
Publication Acceptance Date: 1/15/2021
Publication Date: 3/5/2021
Citation: Shea, K., Berkner, K., Ferland, G., Fu, X., Holden, R., Booth, S.L. 2021. Evidence before enthusiasm: A critical review of the potential cardiovascular benefits of vitamin K. Advances in Nutrition. https://doi.org/10.1093/advances/nmab004.
DOI: https://doi.org/10.1093/advances/nmab004

Interpretive Summary:

Technical Abstract: A protective role for vitamin K in cardiovascular disease (CVD), a leading cause of morbidity and mortality, has been proposed because vitamin K-dependent proteins, such as matrix gla protein (MGP), are present in vascular tissue. MGP functions as a vascular calcification inhibitor - but only when it is carboxylated, which requires vitamin K. There is more than one naturally-occurring form of vitamin K. Phylloquinone (vitamin K1) is found in plant-based foods, whereas menaquinones (vitamin K2) are a class of vitamin K compounds found in animal-based and fermented foods. Phylloquinone and menaquinones are capable of carboxylating MGP and other vitamin K-dependent proteins. In rodent models, high intakes of either phylloquinone or menaquinone reduced vascular calcification. Evidence of the relative importance of phylloquinone and menaquinone to CVD in humans is limited and controversial. In some observational studies, higher dietary menaquinone intake, but not phylloquinone intake, was associated with less coronary artery calcification (CAC, a subclinical manifestation of CVD) and a lower risk for clinical CVD events. These findings have led to claims that menaquinones have unique cardiovascular health benefits, compared to phylloquinone. However, this claim is not supported by the results of the limited number of intervention trials conducted to date. The purpose of this review is to evaluate the strengths and limitations of the available evidence regarding the role of vitamin K in vascular calcification, CVD, and mortality.