Trial: Vitamin K Supplement Curbs Coronary Atherosclerosis

Menaquinone-7 (MK-7) supplementation modestly slowed the progression of coronary artery calcification (CAC) for patients in the placebo-controlled VitaK-CAC trial.

Among people with existing chronic coronary atherosclerosis, CT-derived CAC scores rose to varying degrees between people randomized to the vitamin K homologue or matching placebo, going from 135 AU and 145 AU at baseline, respectively, to 150 AU and 173 AU after 1 year, then finally to 184 AU and 214 AU after 2 years (P=0.02).

Similarly, calcium mass favored those who got once-daily MK-7 supplements: from a baseline level of 25 mg and 26 mg, respectively, calcium mass rose to 28 mg and 33 mg after 1 year and ultimately reached 32 mg and 38 mg after 2 years (P=0.02), reported Peter de Leeuw, MD, PhD, of Maastricht University Medical Center in the Netherlands, and colleagues in JAMA Cardiology.

“The present data support our hypothesis that supplementation with MK-7 during a period of 2 years attenuates coronary artery calcification in individuals with symptomatic CAD [coronary artery disease]. However, the overall effect is modest, and given that the percentage of fast progressors did not differ between the two treatment groups, the clinical significance of our findings remains to be demonstrated,” the authors wrote.

“Only the results of a well-designed outcome trial can provide an answer to the question as to whether the effect of MK-7 is beneficial,” they cautioned.

The menaquinones, also known as vitamin K2, are a family of compounds synthesized by gut bacteria and thought to aid in bone health and cardiovascular health. MK-7 in particular has been shown to be a powerful inhibitor of vascular calcification, with good bioavailability and a relatively long half-life, hence its attractiveness as a supplement for heart protection.

Coupled with CT angiography data, the present results showed that the benefit of MK-7 supplementation seemed limited to reining in the calcification of early to moderately developed noncalcified plaques, whereas it had no effect on CAC progression in advanced plaque or on de novo atherogenesis.

MK-7 treatment also showed no effect on degree of stenosis or number of affected vessels.

VitaK-CAC investigators argued that the true efficacy of MK-7 may have been underestimated in the study, however, noting that study participants had about 80% adherence to their assigned treatment and a 17% dropout rate. What’s more, they were not equipped to study the tiniest calcium deposits in atherosclerotic plaque.

“MK-7 has been suggested to structurally shift macrocalcifications, detectable by CT, to microcalcifications, subtle changes that are not detectable at the plaque level with routine CAC-protocol noncontrast cardiac CT,” explained Michael Blaha, MD, MPH, and Sungwoo Choi, MD, MPH, both of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease in Baltimore, in an accompanying editorial.

“Given what is known about plaque-level calcium density, it is difficult to surmise what the impact on future cardiovascular events might be,” they wrote.

The editorialists stressed the need for more research and cited important questions that remain unanswered regarding MK-7’s effects on atherosclerosis and cardiovascular health.

“Would MK-7 reduce acute coronary syndromes by slowing early propagation of coronary calcification, reducing the mechanical instability thought to be associated with early calcifications? Would MK-7 increase risk by interfering with later plaque stabilization, reversing the favorable process we associate with statin treatment? Or would there be no effect at all since calcification is largely a byproduct along the continuum of plaque development?” Blaha and Choi posed.

VitaK-CAC was a relatively small study conducted at two centers in the Netherlands. Included were 180 symptomatic patients, with CAC scores of 50-400 AU, who were randomized to MK-7 (360 μg daily) or placebo.

Baseline characteristics were statistically similar between groups. Participants had a median age around 60 years and were 42% women. Statin use was reported in 78%, and the average LDL cholesterol level was 77 mg/dL.

Plasma levels of MK-7 rose significantly in the active treatment group (median 0.50 μg/L to 6.56 μg/L, P<0.001), but not among controls.

No significant adverse effects were associated with MK-7 supplements.

The researchers noted that dietary vitamin K consumption had not been tracked for study participants, but was presumably unchanged given the stability in vitamin K1 levels.