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Vitamin K2—a neglected player in cardiovascular health: a narrative review
  1. Essa Hariri1,
  2. Nicholas Kassis1,
  3. Jean-Pierre Iskandar1,
  4. Leon J Schurgers2,
  5. Anas Saad3,
  6. Omar Abdelfattah3,4,
  7. Agam Bansal1,
  8. Toshiaki Isogai3,
  9. Serge C Harb1 and
  10. Samir Kapadia3
  1. 1Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
  2. 2Biochemistry, Maastricht University CARIM School for Cardiovascular Diseases, Maastricht, The Netherlands
  3. 3Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
  4. 4Department of Cardiovascular Medicine, Morristown Medical Center, Morristown, New Jersey, USA
  1. Correspondence to Dr Samir Kapadia; kapadis{at}


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.

  • coronary vessels
  • atherosclerosis
  • heart valve diseases
  • pharmacology
  • clinical
  • biomarkers

Data availability statement

Data sharing not applicable as no datasets generated and/or analysed for this study.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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Data availability statement

Data sharing not applicable as no datasets generated and/or analysed for this study.

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  • EH and NK contributed equally.

  • Contributors EH conceived and designed the study. EH, NK, J-PI and AS collected, analysed and interpreted the data, and performed the literature review. EH, NK and J-PI drafted the manuscript and designed the tables. LJS, TI, SCH, AB and SK revised the manuscript. OA designed the figures. TI, SCH and SK supervised the study. All authors have read and approved the manuscript.

  • Funding This study was made possible by a generous gift from Jennifer and Robert McNeil as unrestricted philanthropic support to the Heart and Vascular Institute, Cleveland Clinic.

  • Disclaimer The funding source had no role in the design or conduct of the study; collection, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

  • Competing interests LJS received an institutional grant from NattoPharma.

  • Provenance and peer review Not commissioned; externally peer reviewed.