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

Randomized, double-blind, placebo-controlled trial conducted in the Netherlands. Adults older than 40 years with type 2 diabetes and preexisting cardiovascular disease were enrolled; for the MK-7 group, 35 participants were randomized and 33 completed follow-up.

Menaquinone-7 (MK-7) 360 μg orally once daily for 6 months, given as two tablets taken with the evening meal. The active product was Nattopharma MK-7; the comparator was placebo.

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.

The trial was relatively small and only 6 months long, limiting power for clinical and imaging outcomes. The primary result was not statistically significant, and 18F-NaF PET activity may be difficult to interpret as a surrogate in this context. Baseline phylloquinone intake was higher in the MK-7 group, and sex data were not reported per arm.