Menaquinone-7 Supplementation and Vascular Calcification in Diabetic Patients

by | Jan 6, 2020 | 2019, Cardiovascular Health, Diabetes, Vitamin K

Written by Angeline A. De Leon, Staff Writer. Menaquinone supplementation, compared to placebo, does not appear to decrease vascular calcification in people with type 2 diabetes and known cardiovascular disease.

cardiovascular healthVascular calcification, involving accumulation of mineral deposits in the vascular system, typically in the inner or middle layer of blood vessels, is associated with higher risk of cardiovascular disease (CVD) 1. Matrix Gla protein (MGP), a vitamin K-dependent protein, plays a prominent role in regulating vascular calcium metabolism and has been shown in epidemiological studies to function as an inhibitor of vascular calcification 2,3. Risk of CVD may be lowered through increased intake of vitamin K 3, but observational studies on the effects of vitamin K intake on vascular calcification have primarily studied vitamin K in the form of phylloquinone (vitamin K-1) 4,5.  Vitamin K-2 (menaquinone) has not been studied in the context of vascular calcification, but is known to be more bioavailable, compared to vitamin K-1, and has been associated with reduced vascular stiffness in intervention studies 6,7. In a 2019 study 8 published in the American Journal of Clinical Nutrition, investigators looked at the effects of menaquinone-7 (MK-7) supplementation in subjects with type 2 diabetes, a population group with high prevalence of vascular calcification 9, using a new technique to identify early signs of active vascular calcification (18sodium fluoride positron emission tomography, 18F-NaF PET).

A total of 68 patients (mean age = 69.1 years) with a diagnosis of type 2 diabetes and pre-existing CVD were enrolled in a randomized, double-blind, placebo-controlled trial in which they were randomized to receive either 360 µg MK-7 or matching placebo daily for 6 months. At baseline and Month 6, 18F-NaF PET was used to measure active vascular calcification in the femoral arterial wall (target-to-background ratio, TBR), and a conventional CT scan was performed to measure calcification mass. Dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) concentrations were also measured as a marker of vitamin K status to confirm treatment compliance. Additional parameters were also measured, including anthropometric measures, ankle-brachial index (ABI, measure of arterial stiffness), blood pressure, and lipid profile based on non-fasting blood samples.

At the end of treatment, TBR was seen to trend towards an increase in the MK-7 group, relative to placebo (p = 0.06), but was not significant. Calcification mass based on CT scans did not appear to increase in the MK-7 group, compared to placebo (p = 0.18). At 3 months, MK-7 was found to significantly reduce inactive MGP concentrations, relative to placebo (-205.6 pmol/L, 95% Confidence Interval: -255.8 to –155.3, p < 0.01), and this effect was sustained after 6 months (-202.7 pmol/L, 95% CI: -272.5 to –132.8, p < 0.01), suggesting a high compliance rate. No significant findings were observed for other study parameters.

Contrary to research hypotheses, findings from the present study did not appear to support an association between MK-7 supplementation and lower vascular calcification. Based on both conventional CT and more exploratory techniques (18F-NaF PET), intake of vitamin K, in the form of menaquinone, was not seen to inhibit vascular calcification. The outcome of this study may be potentially explained by the relatively higher level of vascular calcification observed in the MK-7 group vs. placebo at baseline. It is also worth noting that in the current study, the cohort of diabetic patients did not exhibit significant vitamin K deficiency at the outset. Despite several strengths in the current trial, including a well-controlled design with a high compliance rate, the study also suffered from reduced statistical power due to a high rate of dropout among subjects. Ongoing research, perhaps using higher resolution imaging techniques, is needed to identify the potential therapeutic relationship between vitamin K supplementation and vascular calcification.

Source: Zwakenberg SR, deJong PA, Bartstra JW, et al. The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2019; 110: 883-90. DOI: 10.1093/ajcn/nqz147.

© American Society for Nutrition 2019. All rights reserved. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/)

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Posted January 6, 2020.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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