Daily supplementation with 360 mcg of menaquinone-7, a form of vitamin K2, slowed the progression of coronary artery calcification in a group of individuals with confirmed atherosclerotic cardiovascular disease.
This is a new result A two-year clinical trial just published in JAMA Cardiology By researchers at Maastricht University Medical Center in the Netherlands.
All 180 patients in this study were at high risk for myocardial infarction and had coronary artery calcification (CAC) scores between 50 and 400 Agatston units (AU) based on 128-slice, multidetector CT scans.
Compared with those who took placebo, patients who consistently took vitamin K2 supplements showed a 29% reduction in CAC progression over the 2-year period, based on the Agatston score, and 42% less progression of arterial calcium block.
“This randomized clinical trial found that dietary supplements containing vitamin MK-7 have the potential to reduce new coronary artery calcification in people with mild coronary disease,” Leif M. Vossen, MD, PhD, and colleagues wrote. “This is important because it is an inexpensive, safe and easily purchased product.”
According to Hoogny Vik, MD, PhD, medical and scientific advisor at Gnosis by Lesaffre, the nutritional ingredient that provided MK-7 for the study, Vosine’s findings are “remarkable because we currently have no effective treatments to address the problem of vascular calcification.”
A modest but meaningful impact
However, the authors described the overall effect of supplementation as “modest,” adding that it remains to be seen whether taking MK-7 over a long period would reduce actual fatal and non-fatal cardiovascular events.
At the start of the study, 78% of patients were taking statins, and 67-74% were smokers. The authors note that these points are important when evaluating CAC scores, because statins are known to promote calcification and raise CAC scores. Active and former smokers are also at increased risk of CAC progression, compared with never smokers.
Many participants were also taking angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, calcium channel blockers, and/or diuretics. Nearly two-thirds of them were diagnosed with high blood pressure.
180 men and women were randomly assigned to two groups: one took oral tablets once daily containing 360 mcg of MK-7 (MenaQ7, from Gnosis by Lesaffre); The other took placebo pills similar in size, shape, and color. The 360 mcg dose level was based on data from previous human clinical studies.
The researchers evaluated the patients at 6, 12, and 24 months of age, measured blood vitamin K status, and took repeat CT scans to quantify CAC. They estimated complete compliance with the MK-7 intervention at 80% over 2 years.
Among those who took the supplements, plasma levels of MK-7 increased from an average of 0.5 mcg/L at baseline, to 6.56 mcg/L by the second year. Not surprisingly, MK-7 levels remained steady at just above zero among those who took the placebo.
Weaken progress
MK-7 supplementation did not prevent the development of CAC; AU scores rose steadily in both groups over the 2-year trial period. But the acceleration was much greater in the placebo group.
The median CAC score among placebo-treated patients increased from 145 AU (range 99-217) at baseline, to 173 AU (range 119-297) after the first year, and continued to rise to 214 AU (range 148-344) by the end of the study.
“This randomized clinical trial found that supplements containing vitamin MK-7 have the potential to reduce new coronary artery calcification in people with mild coronary disease.”
Leif Vossen, MD, PhD, Maastricht University
In contrast, AU scores among those taking MK-7 were 135 AU (range 89-226) at the start, 150 AU (range 110-254) after year 1, and 184 (range 122-298) by year 2. That’s a 14% difference between the two groups.
“Regardless of the measure used, all GEE (generalized estimating equations) analyzes showed that CAC score progression over time was significantly lower in the active treatment group than in the placebo group,” Vossen and colleagues reported. They add that the annual increase in CAC scores decreased by 19 AU among MK-7 subjects.
Calcium mass scores showed the same pattern: Although scores increased in both groups, the MK-7 group showed consistently lower calcium mass measurements in year 1 and year 2, compared with those taking placebo.
The Maastricht researchers noted that essentially all of the subjects had visible coronary plaques, but in most cases, these caused only mild stenosis. None of them had life-threatening plaques.
Effect on stenosis
MK-7 supplements appear to mitigate the increase in stenosis severity over time. Vossen reported that 41% of patients in the placebo group showed increases in stenosis severity over the two years, compared to just 33% of those taking MK-7. However, this difference was not statistically significant.
But observed increases in CAC scores over time were significantly associated with increases in the number of previously non-calcified plaques that became partially calcified. Fossen’s team hypothesizes that MK-7 slows calcification in newly developing plaques, but has little effect on already calcified plaques.
Improve flexibility
The idea that vitamin K2 may ameliorate CAC arose from research showing that inhibition of the vitamin K cycle by vitamin K antagonists leads to elevation of decarboxylated Gla protein, and this is strongly associated with arterial calcification.
Leon Schorgers, who heads the Department of Biochemistry at the Cardiovascular Research Institute Maastricht (CARIM) at Maastricht University, and who was involved in the Vosine study, had previously reported that
Supplementation with K2 such as MK-7 can improve vitamin K-dependent MGP activationWhich in turn reduces arterial stiffness and increases their flexibility.
There is also evidence from Placebo-controlled study Among 165 pre- and postmenopausal women, improvements in arterial elasticity after MK-7 supplementation led to clinically meaningful improvements in blood pressure.
Observations from the Vossen experiment support the hypothesis that MK-7 can mitigate CAC to some extent. “Because both the Agatston score and calcium mass point in the same direction, we are confident that MK-7 can slow coronary artery calcification,” they wrote.
But they also emphasize that the overall clinical impact of this intervention remains to be determined in future studies. The MK-7 certainly shows promise, as well as being inexpensive, accessible and extremely safe. But the authors urge caution against overly enthusiastic interpretations of the current data.
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