The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial
What this study found
MK-7 did not reduce vascular calcification. The primary 18F-NaF PET outcome showed a change in TBR of 0.25 versus placebo, with a 95% CI of -0.02 to 0.51 and P = 0.06. CT calcification mass also showed no treatment effect, with a change of 0.50, 95% CI of -0.23 to 1.36, and P = 0.18. Despite a marked reduction in dp-ucMGP at 3 and 6 months, no adverse events were reported and the authors concluded that further work is needed to interpret 18F-NaF PET activity in this setting.
- Study & population
- Randomized, double-blind, placebo-controlled trial conducted in the Netherlands.
- Intervention
- Menaquinone-7 (MK-7) 360 μg orally once daily for 6 months, given as two tablets taken with the evening meal.
- Key limitation
- The trial was relatively small and only 6 months long, limiting power for clinical and imaging outcomes.
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Open PDFOriginal abstract
ABSTRACT 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 clinicaltrials.gov as NCT02839044.