Vitamin K-a Neglected Player in Cardiovascular Health: a Narrative Review

Overview

Journal Open Heart

Publisher BMJ Publishing Group

Specialty Cardiology & Vascular Diseases

Date 2021 Nov 17

PMID 34785587

Citations 13

Authors

Essa Hariri

Nicholas Kassis

Jean-Pierre Iskandar

Leon J Schurgers

Anas Saad

Omar Abdelfattah

Agam Bansal

Toshiaki Isogai

Serge C Harb

Samir Kapadia

Affiliations

Soon will be listed here.

Abstract

Vitamin K 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 K 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 K supplementation. Strengthened by its affordability and Food and Drug Adminstration (FDA)-proven safety, vitamin K supplementation is a viable and promising option to improve cardiovascular outcomes.

Citing Articles

Minerals and Human Health: From Deficiency to Toxicity.

Razzaque M, Wimalawansa S Nutrients. 2025; 17(3).

PMID: 39940312 PMC: 11820417. DOI: 10.3390/nu17030454.

The role of vitamin K2 in cognitive impairment: linking vascular health to brain health.

Roumeliotis S, Kontogiorgos I, de Vries F, Maresz K, Jeanne J, Leivaditis K Front Aging Neurosci. 2025; 16:1527535.

PMID: 39881683 PMC: 11775153. DOI: 10.3389/fnagi.2024.1527535.

Prevalence of Vitamin K2 Deficiency and Its Association with Coronary Artery Disease: A Case-Control Study.

Ahmed S, Yar A, Ghaith A, Alahmadi R, Almaleki F, Alahmadi H Diseases. 2025; 13(1).

PMID: 39851476 PMC: 11764201. DOI: 10.3390/diseases13010012.

Exploring the potential of soapstock over a glycerol in vitamin K2 production by Bacillus subtilis natto: a comparative analysis.

Ansari F, Nouri H, Moghimi H Microb Cell Fact. 2024; 23(1):348.

PMID: 39731131 PMC: 11681655. DOI: 10.1186/s12934-024-02629-1.

Vitamin K: a potential missing link in critical illness-a scoping review.

Paulus M, Drent M, Kouw I, Balvers M, Bast A, van Zanten A Crit Care. 2024; 28(1):212.

PMID: 38956732 PMC: 11218309. DOI: 10.1186/s13054-024-05001-2.

References

Weijs B, Blaauw Y, Rennenberg R, Schurgers L, Timmermans C, Pison L . Patients using vitamin K antagonists show increased levels of coronary calcification: an observational study in low-risk atrial fibrillation patients. Eur Heart J. 2011; 32(20):2555-62. DOI: 10.1093/eurheartj/ehr226. View

Juanola-Falgarona M, Salas-Salvado J, Martinez-Gonzalez M, Corella D, Estruch R, Ros E . Dietary intake of vitamin K is inversely associated with mortality risk. J Nutr. 2014; 144(5):743-50. DOI: 10.3945/jn.113.187740. View

Shea M, Booth S, Weiner D, Brinkley T, Kanaya A, Murphy R . Circulating Vitamin K Is Inversely Associated with Incident Cardiovascular Disease Risk among Those Treated for Hypertension in the Health, Aging, and Body Composition Study (Health ABC). J Nutr. 2017; 147(5):888-895. PMC: 5404216. DOI: 10.3945/jn.117.249375. View

Zwakenberg S, Burgess S, Sluijs I, Weiderpass E, Beulens J, van der Schouw Y . Circulating phylloquinone, inactive Matrix Gla protein and coronary heart disease risk: A two-sample Mendelian Randomization study. Clin Nutr. 2019; 39(4):1131-1136. PMC: 7612948. DOI: 10.1016/j.clnu.2019.04.024. View

Hermans M, Vermeer C, Kooman J, Brandenburg V, Ketteler M, Gladziwa U . Undercarboxylated matrix GLA protein levels are decreased in dialysis patients and related to parameters of calcium-phosphate metabolism and aortic augmentation index. Blood Purif. 2007; 25(5-6):395-401. DOI: 10.1159/000108629. View

Braam L, Dissel P, Gijsbers B, Spronk H, Hamulyak K, Soute B . Assay for human matrix gla protein in serum: potential applications in the cardiovascular field. Arterioscler Thromb Vasc Biol. 2000; 20(5):1257-61. DOI: 10.1161/01.atv.20.5.1257. View

Bar A, Kus K, Manterys A, Proniewski B, Sternak M, Przyborowski K . Vitamin K-MK-7 improves nitric oxide-dependent endothelial function in ApoE/LDLR mice. Vascul Pharmacol. 2019; 122-123:106581. DOI: 10.1016/j.vph.2019.106581. View

Parker B, Schurgers L, Vermeer C, Schiller N, Whooley M, Ix J . The association of uncarboxylated matrix Gla protein with mitral annular calcification differs by diabetes status: The Heart and Soul study. Atherosclerosis. 2009; 210(1):320-5. PMC: 2862076. DOI: 10.1016/j.atherosclerosis.2009.11.023. View

Knapen M, Jardon K, Vermeer C . Vitamin K-induced effects on body fat and weight: results from a 3-year vitamin K2 intervention study. Eur J Clin Nutr. 2017; 72(1):136-141. DOI: 10.1038/ejcn.2017.146. View

10.

Karsli-Ceppioglu S, Yazar S, Keskin Y, Karaca M, Luleci N, Yurdun T . Association of Genetic Polymorphisms in the Gene with Coronary Artery Disease and Serum MGP Levels. Balkan J Med Genet. 2020; 22(2):43-50. PMC: 6956629. DOI: 10.2478/bjmg-2019-0020. View

11.

Fusaro M, Cianciolo G, Brandi M, Ferrari S, Nickolas T, Tripepi G . Vitamin K and Osteoporosis. Nutrients. 2020; 12(12). PMC: 7760385. DOI: 10.3390/nu12123625. View

12.

Zwakenberg S, den Braver N, Engelen A, Feskens E, Vermeer C, Boer J . Vitamin K intake and all-cause and cause specific mortality. Clin Nutr. 2016; 36(5):1294-1300. DOI: 10.1016/j.clnu.2016.08.017. View

13.

Mansour A, Ahdab R, Daaboul Y, Korjian S, Morrison D, Hariri E . Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case-Control Study. Headache. 2019; 60(3):589-599. DOI: 10.1111/head.13715. View

14.

Mayer Jr O, Bruthans J, Seidlerova J, Karnosova P, Materankova M, Gelzinsky J . The coincidence of low vitamin K status and high expression of growth differentiation factor 15 may indicate increased mortality risk in stable coronary heart disease patients. Nutr Metab Cardiovasc Dis. 2020; 31(2):540-551. DOI: 10.1016/j.numecd.2020.09.015. View

15.

Hwang D, Dempsey A, Lee C, Liew C . Identification of differentially expressed genes in cardiac hypertrophy by analysis of expressed sequence tags. Genomics. 2000; 66(1):1-14. DOI: 10.1006/geno.2000.6171. View

16.

Wong T, Klein R, Nieto F, Klein B, Sharrett A, Meuer S . Retinal microvascular abnormalities and 10-year cardiovascular mortality: a population-based case-control study. Ophthalmology. 2003; 110(5):933-40. DOI: 10.1016/S0161-6420(03)00084-8. View

17.

Riphagen I, Keyzer C, Drummen N, de Borst M, Beulens J, Gansevoort R . Prevalence and Effects of Functional Vitamin K Insufficiency: The PREVEND Study. Nutrients. 2018; 9(12). PMC: 5748784. DOI: 10.3390/nu9121334. View

18.

Caluwe R, Vandecasteele S, Van Vlem B, Vermeer C, De Vriese A . Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study. Nephrol Dial Transplant. 2013; 29(7):1385-90. DOI: 10.1093/ndt/gft464. View

19.

Fraser J, Price P . Lung, heart, and kidney express high levels of mRNA for the vitamin K-dependent matrix Gla protein. Implications for the possible functions of matrix Gla protein and for the tissue distribution of the gamma-carboxylase. J Biol Chem. 1988; 263(23):11033-6. View

20.

Wei F, Trenson S, Monney P, Yang W, Pruijm M, Zhang Z . Epidemiological and histological findings implicate matrix Gla protein in diastolic left ventricular dysfunction. PLoS One. 2018; 13(3):e0193967. PMC: 5846787. DOI: 10.1371/journal.pone.0193967. View