Press Release 12/19/2013: MenaQ7® Vitamin K2 Supplementation May Benefit Dialysis Patients by Inhibiting Vascular Calcification
NattoPharma has announced the publication of a new study performed in collaboration with OLV Hospital, Belgium, St. Jan Hospital, Belgium and VitaK, University of Maastricht, the Netherlands, published by Nephrology Dialysis Transplantation. doi: 10.1093/ndt/gft464 .
Haemodialysis patients suffer from early and accelerated vascular calcification which is predictive for cardiovascular disease and all-cause mortality in this population. The vitamin K-dependent matrix GLA protein (MGP) is one of the most potent inhibitors of vascular calcification, and Dialysis patients have high levels of the inactive form, or undercarboxylated MGP. Thus, this patient population may benefit from Vitamin K2 as menaquinone-7 supplementation to activate MGP and prevent vascular calcification.
“Vascular calcification is a significant problem for dialysis patients. In fact, without transplant, it could be considered a terminal condition for this population. Our hope is that Vitamin K2 supplementation may slow this process and improve not only the quality, but quantity of life for these patents, ” says investigator An S. De Vriese of the Division of Nephrology and Infectious Diseases, AZ St.-Jan Hospital.
Previously vascular calcification was considered to be an entirely passive process. However it is now widely recognized that it is an actively regulated process implying death and damage of vascular smooth muscle cells (VSMCs) and transformation of these cells into osteoblast-like cells (bone producing cells). Deficiencies in calcification inhibitors – where carboxylated (active) MGP is one of the strongest, and where Vitamin K2 activates MGP – are major explanations for calcification in the vessel wall.
To determine the optimal dose of Vitamin K2 as menaquinone-7 (MK-7) for MGP activation, 200 chronic haemodialysis patients were recruited to randomly receive 360, 720 or 1080 μg of MK-7 (MenaQ7 ® ) three times weekly for 8 weeks. Vitamin K1 (phylliquone) and K2 from food sources was estimated based on a detailed questionnaire. Vitamin K1 was not associated with MGP activity. MK-7 levels in the patient groups were correlated with the reduction in the concentrations of inactive (undercarboxylated) MGP after 8 weeks. The reductions were 17, 33 and 46% in the respective K2 groups.
“This study demonstrates the benefits of vitamin K2 in the activation of MGP, a potent inhibitor of vascular calcification, ” says Hogne Vik, CEO of NattoPharma. “While dialysis patients are significantly prone to calcification, we know from population- and in vivo studies, that improving vitamin K2 status results in less arterial calcification and improved cardiovascular outcomes. A three-year interventional study with MenaQ7® actually showed an improvement in arterial elasticity in healthy postmenopausal women.”
The authors concluded that vitamin K2 supplementation may be a novel approach to prevent vascular calcifications in chronic haemodialysis patients.
About NattoPharma and MenaQ7®
As a biotechnology-based nutraceutical company, NattoPharma is the worldwide innovator of Vitamin K2 menaquinone-7. Its brand MenaQ7® is supported by a global IPR portfolio and research substantiating clear efficacy for bone and cardiovascular health. NattoPharma has since 2007 been in a research and development collaboration with VitaK, University of Maastricht, the Netherlands, working to substantiate the health benefits of vitamin K2.
Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study*
Nephrology Dialysis Transplantation, Advance Access, 10.1093/ndt/gft464
Rogier Caluwé 1⇑, Stefaan Vandecasteele 2, Bruno Van Vlem 1, Cees Vermeer3 and An S. De Vriese2
1Division of Nephrology, OLV Hospital, Aalst, Belgium
2Division of Nephrology and Infectious Diseases, AZ St.-Jan Hospital, Brugge, Belgium
3VitaK, Maastricht University, EV Maastricht, the Netherlands
Correspondence and offprint requests to: Rogier Caluwé; E-mail: rogier.caluwe at olvz-aalst.be
↵* The results presented in this paper have not been published previously in whole or part, except in abstract form in November 2012 as a poster abstract at ASN Kidney week in San Diego, California (SA-PO618).
Background Haemodialysis patients suffer from accelerated vascular calcification. The vitamin K-dependent matrix Gla protein (MGP) is one of the most powerful inhibitors of vascular calcification. Haemodialysis patients have high levels of the inactive form of MGP (desphosphorylated-uncarboxylated-MGP, dp-uc-MGP) and may benefit from pharmacological doses of vitamin K2 (menaquinone) to improve the calcification inhibitory activity of MGP.
Methods To determine the optimal dose of menaquinone-7 (MK-7) for MGP activation, 200 chronic haemodialysis patients were recruited to randomly receive 360, 720 or 1080 µg of MK-7 thrice weekly for 8 weeks. Dp-uc-MGP was measured at baseline and after 8 weeks. Dietary intake of vitamin K1 (phylloquinone) and menaquinone was estimated based on a detailed questionnaire.
Results At baseline, dp-uc-MGP was not associated with phylloquinone intake (P = 0.92), but correlated inversely with menaquinone intake (P = 0.023). MK-7 supplementation dose dependently reduced dp-uc-MGP. The levels decreased by 17, 33 and 46% in the respective groups.
Drop-outs were mainly due to gastrointestinal side-effects related to the unpleasant smell of the tablets.
Conclusions Chronic haemodialysis patients have high levels of inactive MGP, possibly related to a low dietary vitamin K intake. Pharmacological doses of MK-7 dose-dependently reduce dp-uc-MGP. Menaquinone supplementation may be a novel approach to prevent vascular calcifications in chronic haemodialysis patients.
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