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Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale
Liv M Vossen1,2, Leon J Schurgers3, Bernard J van Varik4
1Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht 6229HX, The Netherlands. liv.vossen@mumc.nl.
Insights
Vitamin K supplementation, specifically menaquinone-7 (MK-7), may slow coronary artery calcification (CAC) progression in patients with coronary artery disease (CAD). The VitaK-CAC trial investigates MK-7
Area of Science:
- Cardiovascular Medicine
- Nutritional Science
- Biochemistry
Background:
- Coronary artery calcification (CAC) is an early indicator of atherosclerosis and a predictor of cardiovascular disease (CVD).
- Arterial calcification results from dysregulated calcification processes, inhibited by vitamin K-dependent matrix Gla protein (MGP).
- Vitamin K antagonists (VKA) increase uncarboxylated MGP (ucMGP), linked to arterial calcification, suggesting a role for vitamin K in prevention.
Purpose of the Study:
- To investigate the effect of menaquinone-7 (MK-7) supplementation on the progression of coronary artery calcification (CAC) in patients with coronary artery disease (CAD).
- To evaluate MK-7's potential to slow or halt CAC progression, offering a novel therapeutic strategy for vascular calcification and CVD.
Main Methods:
- The VitaK-CAC trial is a 24-month, double-blind, randomized, placebo-controlled study.
- Participants with coronary artery disease (CAD) and a baseline Agatston CAC score between 50 and 400 were randomized.
- Intervention group received 360 micrograms of MK-7 daily, while the control group received a placebo.
Main Results:
- Primary endpoint: difference in CAC score progression between MK-7 and placebo groups over 24 months.
- Secondary endpoints: changes in arterial structure, function, and relevant biomarkers.
- Hypothesis: MK-7 supplementation will reduce CAC progression compared to placebo.
Conclusions:
- The VitaK-CAC trial will determine if MK-7 supplementation can mitigate CAC progression.
- Findings may establish MK-7 as a treatment for vascular calcification, reducing cardiovascular disease risk.
- This research addresses the imbalance in calcification regulation, potentially impacting atherosclerosis management.
Abstract:
Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months. The primary endpoint is the difference in CAC-score progression between both groups. Secondary endpoints include changes in arterial structure and function, and associations with biomarkers. We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD.
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