Low Vitamin K2 Status is a Risk Factor for Hardening of the Arteries – Presented at the American Society of Nephrology Convention
14 November 2008, Morristown, NJ
PL Thomas and NattoPharma, Norway, announced significant exposure and discussion of Vitamin K2 and its role in promoting cardiovascular health at the American Society of Nephrology’s Renal Week 2008 in Philadelphia. Of note, four key presentations, including two abstracts, a poster and a feature presentation by Leon Schurgers, PhD, Senior Scientist at the Cardiovascular Research Institute Maastricht (CARIM) at the University of Maastricht, all discussed the significance of adequate vitamin K2 intake for the prevention of vascular calcification in both healthy and diseased populations. The source of natural vitamin K2 used in the studies was MenaQ7 natural vitamin K2.
At the Vascular Calcification in Chronic Kidney Disease Symposium, Dr Schurgers explained: “Calcification of the arteries seen in chronic kidney disease is the same type of calcification which is found in aging population. The accumulation of calcium salts in the arteries results in stiffening and increase fragility. This might be considered a “silent killer” as hardening of the arteries develops without any symptoms over time. At this meeting evidence was provided that the process of calcification is an actively regulated process and that adequate vitamin K2 intake can prevent this process and potentially reduce this risk factor.”
Other activities of note: An abstract by Dr. Ralf Westenfeld, et al. with 53 hemodialysis patients compared to 102 control patients revealed that hemodialysis patients are characterized by impaired mineralization inhibitors, meaning they do not have the their ability to protect against arterial calcification. These patients have a significant amount of inactive Matrix GLA Protein (MGP) a vitamin K-dependent protein which is the most potent inhibitor of vascular calcification known. Six weeks of vitamin K2 supplementation increased active MGP levels in these patients in a dose dependent manner, suggesting that disturbed calcification inhibitory activity in the vasculature may be improved by dietary vitamin K2 supplementation.
Yet another abstract, by Cranenburg, et. al., with 54 hemodialysis patients compared to 44 healthy controls looked at vitamin K2 supplementation to address protection against arterial calcification due to the synthesis of immature, inactive MGP. Vitamin K2-administration rapidly eliminated the inactive MGP species, suggesting improved calcification-inhibitory activity. Therefore, also in this study vitamin K2 supplementation showed that it is possible to positively influence the major calcification inhibitor MGP. This may have interesting potential for this group of patients as they suffer from high cardiovascular morbidity and mortality. Finally, a poster presented by Krueger, et. al., discussed the development of an animal model to study calcification inhibitors. In this new model, vascular calcification is induced by adding warfarin to the diet, blocking vitamin K and inhibiting MGP from preventing calcium accumulation. By adding vitamin K2 to the diet simultaneously with warfarin, the calcification was inhibited. This work supports the concept that vitamin K2 is important to protect the arteries and soft tissues from calcification, and even could lead to regression of pre-formed calcification.
Inhibition of Vascular Calcification
Moderate to severe vascular calcifications are found in approximately 60-80% of patients undergoing hemodialysis, resulting in 20-fold higher risk of cardiovascular mortality (than in healthy population).
Vitamin K2 is the form of vitamin K strongly associated with the vitamin K-dependent protein MGP in human calcium metabolism. Studies show that K2 is required to activate MGP and therefore to restrain circulating calcium from depositing within the vessel walls. Without adequate vitamin K2 status, the biological function of MGP is impaired, contributing to the development of arterial calcification resulting in stiffness and fragility of blood vessels, thus increasing the risk of fatal cardiovascular event.
The Rotterdam Study from 2004 found increased intake of Vitamin K2 from dietary sources significantly reducing the incidence of arterial calcification and the risk of CHD mortality by 50% as compared to low dietary vitamin K2 intake. Conversely, dietary vitamin K1 had no effect.
Presented at ASN Renal Week 2008
Vitamin K2 Supplementation Reduces the Elevated Inactive Form of the Calcification Inhibitor Matrix GLA Protein in Hemodialysis Patients Ralf Westenfeld, Thilo KrÃ¼ger, Georg Schlieper, Ellen Cranenburg, Stefan Heidenreich, Stefan Holzmann, Cees Vermeer, Markus Ketteler, JÃ¼rgen Floege, Leon J. Schurgers. Department of Nephrology, RWTH University Hospital, Aachen, Germany; Cardiovascular Reseach Institute and VitaK BV, University, Maastricht, Netherlands; Kfh Dialyse, Aachen, Germany; Dialysezentrum, Erkelenz, Germany; Nephrology, Klinikum, Coburg, Germany.
Poor Vitamin K Status and Immature MGP Species Are Associated with the Progression of Calcification in Hemodialysis Patients Ellen C. M. Cranenburg, Vincent M. Brandenburg, Cees Vermeer, Elke Magdeleyns, Markus Ketteler, Leon J. Schurgers. VitaK and CARIM, Maastricht University, Maastricht, Netherlands; Department of Nephrology and Clinical Immunology, RWTH University Hospital, Aachen, Germany; Nephrology, Klinikum Coburg, Coburg, Germany.
Warfarin-Induced Calcification in Mice – A Novel Tool To Investigate Interactions of Calcification Inhibitors Thilo Krueger, L. Schurgers, G. Schlieper, V. Brandenburg, B. Fekete, C. Schafer, M. Ketteler, W. Jahnen-Dechent, J. Floege, R. Westenfeld. Nephrology, University Clinic Aachen, Aachen, Germany; VitaK, University of Maastricht, Maastricht, Netherlands; Nephrology, University of Budapest, Budapest, Hungary; Biomedical Engineering, University of Aachen, Aachen, Germany; Nephrology, Hospital Coburg, Coburg, Germany.
MenaQ7 provides Natural Vitamin K2 as an extract of natto, a fermented soy food from Japan. Natto is particularly rich in the highly bio-available form of vitamin K2, menaquinone-7 (MK-7). MenaQ7 is the commercially available Natural Vitamin K2 with guaranteed actives and stability, clinical substantiation and international patents awarded and pending.