The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: A randomized, double-blind, placebo-controlled trial

S. R. Zwakenberg, P. A. De Jong, J. W. Bartstra, R. Van Asperen, J. Westerink, H. De Valk, R. H.J.A. Slart, G. Luurtsema, J. M. Wolterink, G. J. De Borst, J. A. Van Herwaarden, M. A. Van De Ree, L. J. Schurgers, Y. T. Van Der Schouw, J. W.J. Beulens

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Background: Vitamin K occurs in the diet as phylloquinone and menaquinones. Observational studies have shown that both phylloquinone and menaquinone intake might reduce cardiovascular disease (CVD) risk. However, the effect of vitamin K on vascular calcification is unknown. Objectives: The aim of this study was to assess if menaquinone supplementation, compared to placebo, decreases vascular calcification in people with type 2 diabetes and known CVD. Methods: In this double-blind, randomized, placebo-controlled trial, we randomly assigned men and women with type 2 diabetes and CVD to 360 μg/d menaquinone-7 (MK-7) or placebo for 6 mo. Femoral arterial calcification at baseline and 6 mo was measured with 18sodium fluoride positron emission tomography (18F-NaF PET) scans as target-to-background ratios (TBRs), a promising technique to detect active calcification. Calcification mass on conventional computed tomography (CT) scan was measured as secondary outcome. Dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) concentrations were measured to assess compliance. Linear regression analyses were performed with either TBR or CT calcification at follow-up as the dependent variable, and treatment and baseline TBR or CT calcification as independent variables. Results: We randomly assigned 35 patients to the MK-7 group (33 completed follow-up) and 33 to the placebo group (27 completed follow-up). After the 6-mo intervention, TBR tended to increase in the MK-7 group compared with placebo (0.25; 95% CI: -0.02, 0.51; P = 0.06), although this was not significant. Log-transformed CT calcification mass did not increase in the intervention group compared with placebo (0.50; 95% CI: -0.23, 1.36; P = 0.18). MK-7 supplementation significantly reduced dp-ucMGP compared with placebo (-205.6 pmol/L; 95% CI: -255.8, -155.3 pmol/L). No adverse events were reported. Conclusion: MK-7 supplementation tended to increase active calcification measured with 18F-NaF PET activity compared with placebo, but no effect was found on conventional CT. Additional research investigating the interpretation of 18F-NaF PET activity is necessary. This trial was registered at as NCT02839044.

Original languageEnglish
Pages (from-to)883-890
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Issue number4
Publication statusPublished - 1 Oct 2019


  • cardiovascular disease
  • diabetes
  • menaquinone-7
  • vascular calcification
  • vitamin K

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