Daily supplementation with 360 μg of menaquinone-7, a form of vitamin K2, slowed the progression of coronary artery calcification in a cohort of individuals with confirmed atherosclerotic cardiovascular disease.
That’s the upshot of a new two-year clinical trial just published in JAMA Cardiology by researchers based at the Maastricht University Medical Center, Netherlands.
All 180 patients in this study were at elevated risk for myocardial infarction, and had baseline coronary artery calcification (CAC) scores between 50 and 400 Agatston units (AU) based on 128-slice, multiple detector CT scans.
Compared with those on placebo, the patients who consistently took the vitamin K2 supplement showed a 29% lower CAC progression over the two-year period, based on Agatston score, and 42% less progression in arterial calcium mass.
“This randomized clinical trial found that supplementation with vitamin MK-7 has the potential to reduce new coronary artery calcification in people with mild coronary disease,” write Liv M. Vossen, MD, PhD, and colleagues. “This is relevant because it is an inexpensive and safe product that can easily be purchased.”
According to Hogne Vik, MD, PhD, a medical and scientific advisor at Gnosis by Lesaffre, the nutraceutical ingredient that provided the MK-7 for the study, Vossen’s findings are, “remarkable as we currently do not have any effective treatments to address the issue of vascular calcification.”
Modest But Meaningful Effect
That said, the authors characterized the overall impact of supplementation as “modest,” adding that it remains to be seen whether taking MK-7 over an extended period would reduce actual fatal and non-fatal cardiovascular events.
At the outset of the study, 78% of the patients were taking statin drugs, and 67-74% were smokers. The authors note that these points are important when assessing CAC outcomes, because statins are known to promote calcification and raise CAC scores. Active and past smokers are also at risk of increased CAC progression, compared with never-smokers.
Many of the participants were also taking ACE inhibitors, β-blockers, calcium channel blockers, and/or diuretics. Roughly two-thirds had been diagnosed with hypertension.
The 180 men and women were randomized to two groups: one took once-daily oral tablets containing 360 μg of MK-7 (MenaQ7, from Gnosis by Lesaffre); the other took placebo tablets similar in size, shape, and color. The 360 μg dose level was based on data from previous human clinical studies.
The researchers evaluated the patients at 6, 12, and 24 months, measuring serum vitamin K status, and capturing repeated CT scans to quantify CAC. They estimated full compliance with the MK-7 intervention to be 80% over the two-year stretch.
Among those taking the supplements, plasma levels of MK-7 rose from a median of 0.5 μg/L at baseline, to 6.56 μg/L by the second year. Not surprisingly, MK-7 levels remained flat at just over zero among those on placebo.
Attenuating Progression
MK-7 supplementation did not avert CAC progression; AU scores rose steadily in both groups over the two-year trial period. But the acceleration was far greater in the placebo group.
The median CAC score among the placebo-treated patients went from 145 AU (range 99-217) at baseline, to 173 AU (range 119-297) after the first year, and continued rising to 214 AU (range 148-344) by the close of the study.
“This randomized clinical trial found that supplementation with vitamin MK-7 has the potential to reduce new coronary artery calcification in people with mild coronary disease.”
Liv Vossen, MD, PhD, Maastricht University
In contrast, AU scores among those taking MK-7 were 135 AU (range 89-226) at the outset, 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.
“Irrespective of what scale was used, all GEE (generalized estimaging equations) analyses showed that the evolution of the CAC score over time was significantly less in the active treatment group compared with the placebo group,” report Vossen and colleagues. They add that the yearly increase in CAC scores was reduced by 19 AU among the MK-7 subjects.
Calcium mass scores showed the same pattern: though the scores increased in both groups, the MK-7 group showed consistently lower calcium mass measurements at year 1 and year 2, compared with those on placebo.
The Maastricht researchers note that at baseline, all subjects had visible coronary plaques but that, in most cases, these caused only mild stenosis. None had life-threatening plaques.
Impact on Stenosis
MK-7 supplementation did appear to mitigate the increase in stenosis severity over time. Vossen reports that 41% of the patients in the placebo group showed increases in stenosis severity over the two years, compared with just 33% of those taking MK-7. However, this difference was not statistically significant.
But the observed increases in CAC scores over time did correlate significantly with increases in the number of previously non-calcified plaques that became partially calcified. The Vossen team hypothesizes that MK-7 slows calcification in newly developing plaques, but has little effect on already calcified plaques.
Improving Elasticity
The notion that Vitamin K2 might attenuate CAC arose from research showing that inhibition of the vitamin K cycle by vitamin K antagonists results in elevations of uncarboxylated matrix Gla protein, and this is strongly associated with arterial calcification.
Leon Schurgers, who chairs the Department of Biochemistry at the Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, and who participated in the Vossen study, had previously reported that supplementation with K2 as MK-7 could improve vitamin K–dependent MGP activation, which in turn, reduces arterial stiffness and increases elasticity.
There’s also evidence from a placebo-controlled study of 165 peri- and post-menopausal women, that the improvements in arterial elasticity following MK-7 supplementation led to clinically meaningful improvements in blood pressure.
The observations from the Vossen trial support the hypothesis that MK-7 can mitigate CAC to some degree. “As both the Agatston and the calcium mass score pointed in the same direction, we are confident that MK-7 can slow down coronary calcification,” they write.
But they also stress that the overall clinical impact of this intervention remains to be determined in future studies. MK-7 is definitely promising, as well as being inexpensive, easily accessible, and very safe. But the authors urge caution against overly enthusiastic interpretations of the current data.
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