Research links vitamin K2 and D to predictor of cardiovascular disease

By Nikki Hancocks

- Last updated on GMT

© BrianAJackson / Getty
© BrianAJackson / Getty

Related tags Research Vitamins Cardiovascular disease

A new data analysis suggests a link between vitamin K2 MK-7 and vitamin D supplementation and a reduction in coronary artery calcification (CAC) development—a strong predictor of heart attack and cardiovascular mortality in high-risk patients and statin users.

Published in JACC Advances​, the double-blinded, placebo-controlled clinical trial tested the impact of supplementing with Kappa Bioscience’s vitamin K2 MK-7 solution (K2VITAL DELTA) alongside vitamin D3, concluding that the supplements may help to slow the progression of CAC in those with high baseline scores and those on statins.

“These findings add to a growing bank of evidence demonstrating the benefits of vitamin K2 MK-7 for heart health, but this is the first clinical trial documenting effects directly on calcium deposits in the coronary arteries,” said Trygve Bergeland, Director Nutrition Science, Kappa Bioscience, owned by Balchem​.

“We’re thrilled to be at the forefront of such pivotal research in the cardiovascular space and for our K2VITAL solution to be at the centre of it all. We’ve been interested in the science behind ‘The Perfect Pair’—that is vitamin K2 MK-7 supplementation in combination with vitamin D—for some time now.”

The study was independently conducted by researchers from hospitals across Denmark, as well as the Biomedical Imaging Research Institute in Los Angeles, California.

“The positive discoveries from the AVADEC trial signal an exciting advancement in our continued efforts to understand the full benefits of this vitamin combination,” Bergeland added.

Principal investigator of the AVADEC study, Professor Axel Diederichsen from the Odense University Hospital in Denmark, points out that emerging science shows that vitamin K2 and D supplementation play an important role in heart health, but there is limited research that delves deeper into the mechanism of action behind this.

"We were interested in exploring this further, particularly the effects of vitamin K2 deficiency on coronary artery calcifications, which we know is strongly associated with higher risk of heart attack and death," he explained.

“Although this is just the beginning of our research in this specific field, the initial findings from our subgroup analysis are promising and pave the way for future innovation and research in the cardiovascular space. We’ve already started the preparations for our next trial with the objective to confirm our findings of the AVADEC trial—so watch this space!” 

Heart attack prevalence and research

Acute myocardial infarction, aka heart attack, is one of the leading causes of death in the developed world, with a prevalence approaching three million people worldwide, annually​. CAC—the buildup of calcium in the arteries that supply blood to the heart—is a strong predictor of heart attacks.

The Aortic Valve Decalcification Trial, commonly known as the AVADEC study​, was commissioned in 2018 to investigate the effects of vitamin K supplementation through the quantification of calcium deposits in the aortic valve as well as the coronary arteries.

In the study, 389 male patients (mean age 71 years) from four Danish hospitals were randomised to supplement with vitamin K2 (720 μg/day) and D (25 μg/day) vs placebo in a multi-center, double-blinded controlled trial.

Patients with previous heart valve surgery, moderate aortic stenosis, treatment with vitamin K antagonists, calcium and phosphate metabolism or coagulation system disorders were excluded.

Patients were followed for 24 months undergoing clinical examination with blood sample collection every six months. A biobank was established with blood samples at baseline and after 1 and 2 years of follow-up. Analysis of plasma dp-ucMGP in the biobank samples was used as a proxy for vitamin K status.

Participants underwent both noncontrast electrocardiogram-gated CT for calcium scoring at baseline, 1-year and 2-year follow-up, as well as contrast-enhanced electrocardiogram-gated coronary CT angiography​ (CCTA) at baseline and 2-year follow-up. 

The secondary outcome of the study was the effect of vitamin K2 and D supplementation on CAC progression, as well as changes in plaque composition and coronary artery stenosis, in a randomized controlled setting.

Analysing high-risk patients

The new study reports CAC progression in 304 participants (155 in the control group and 149 in the intervention group), excluding patients with ischemic heart disease (reduced blood flow to the heart). The purpose of this exclusion from the primary population was to optimize the CAC evaluations.

CAC, coronary plaque volume and 'safety events' (heart attacks, procedures and all-cause mortality) were evaluated in the entire group and in two subgroups - statin users and those with baseline CAC scores above 400 AU. 

In the total group, the progression of CAC score after two years was not different between the intervention and placebo group.  

However, in the subgroup of participants with baseline CAC score above 400 AU, a significant difference at 24-month follow-up was shown (P​ = 0.047), safety events were fewer in participants receiving supplementation (1.9% vs 6.7%, P​ = 0.048), which the authors say is hypothesis-generating for future studies.

What's more, when exploring the group of statin users, the intervention with K2+D significantly slowed down the progression of calcification (P=0.048). This suggests that statin users may benefit from K2+D supplementation. 

The authors note this probably relates to the fact that these participants also had higher CAC scores at baseline (numbers not presented).

"No randomized controlled trials​ have managed to show a reduction in CAC progression to date," the authors wrote. "It has previously been described that baseline CAC score predicts progression by an annual increase of 20% to 25%. 

"As expected, the high-risk participants with CAC scores over 400 AU had the highest absolute increase in CAC score, but they also seemed to have the greatest effect of vitamin K2 supplementation. It is possible that the effect is simply most evident in the participants with the most notable progression and that the follow-up period was too short to detect a difference in the participants with lower CAC scores."

The authors emphasized that this finding was based on a safety endpoint and the study was not powered for this outcome, leaving this a possible coincidental finding. Hence, more research is needed to discover the benefits of this supplement in a high-risk population.

To confirm the results of the AVADEC research, the researchers have initiated a follow-up study called DANCODE​. The main aim of DANCODE is to investigate the effect of MK-7 and vitamin D on progression of CAC in men and women with a CAC score ≥400 AU at baseline, in a Danish multicentre randomized controlled trial. 

Source: JACC Advances
doi: 10.1016/j.jacadv.2023.100643
"Effects of Vitamin K2 and D Supplementation on Coronary Artery Disease in Men: A RCT"
Authors: Selma Hasific et al.

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