Two Years of Menaquinone-7 Supplementation and Coronary Artery Calcification (paper June 10 2026)

#1

https://jamanetwork.com/journals/jamacardiology/article-abstract/2850256

This is sadly behind a paywall.

Key Points

Question What is the effect of menaquinone-7 on coronary artery calcification?

Findings In this randomized clinical trial that included 180 adults, menaquinone-7 significantly attenuated coronary artery calcification compared with placebo.

Meaning In this study, menaquinone-7 slowed the progression of coronary artery calcification, but a large, prospective trial with hard clinical outcomes is needed to ascertain whether supplementation with menaquinone-7 is beneficial among patients with coronary artery disease.

Abstract

Importance Vitamin K supplementation can reduce progression of vascular calcification in patients with diabetes or end-stage kidney disease. Presently, it is unknown whether vitamin K is also beneficial in patients with symptomatic atherosclerotic coronary artery disease (CAD).

Objective To evaluate whether supplementation with the vitamin K homologue menaquinone-7 (MK-7) for a period of 2 years attenuates the progression of coronary artery calcification (CAC) compared with placebo.

Design, Setting, and Participants This randomized placebo-controlled clinical trial including symptomatic patients with CAC score between 50 and 400 Agatston units (AU) with 2 years of follow-up (VitaK-CAC study). The study was conducted at 1 university hospital and 1 community-dwelling hospital in the Netherlands. Data were collected from January 2012 through October 2022 with a few interruptions; analyses were performed from January 2023 to April 2024.

Intervention Supplementation with either the vitamin K homologue menaquinone-7 (MK-7) in a daily dose of 360 µg or identical placebo.

Main Outcomes and Measures The primary outcome of the study was the evolution of the CAC score and calcium mass at 1 and 2 years of follow-up, as measured with computed tomography (CT) scanning. Additionally, CT angiography was performed. The incidence of new calcifications was a secondary outcome measure. Data were analyzed using a generalized estimation equations model, adjusted for covariates.

Results Altogether, 180 patients could be randomized (90 patients per group), with 85 patients receiving MK-7 (median [IQR] age, 59 [54-65] years; 36 [42%] female) and 82 receiving placebo (median [IQR] age, 61 [54-65] years; 34 [42%] female). Baseline characteristics were comparable for the 2 groups. Plasma levels of MK-7 rose significantly in the active treatment group (median [IQR], 0.50 [0.32-0.77] µg/L to 6.56 [2.04-10.35] µg/L; P < .001). In the placebo group, CAC scores increased from a median (IQR) of 145 (99-217) AU to 173 (119-297) AU after the first year and to 214 (148-344) AU after the second. In the active treatment group, these values were 135 (89-226), 150 (110-254) and 184 (122-298) AU, respectively. The difference between the groups was significant (P = .02), even after adjustment for covariates. A similar result was seen for calcium mass. The increase in CAC score correlated with the number of noncalcified plaques that became partially calcified during the study (R 2 = 0.17; P = .04). No significant adverse effects were observed.

Conclusions and Relevance The findings of this study suggest that supplementation with MK-7 for 2 years may slow calcification in noncalcified plaques of patients with symptomatic CAD. The clinical significance of this finding in terms of plaque stability remains to be determined.

JH

The menaquinones and in particular menaquinone-7 are some of my favourite molecules. I have been reading up on the mechanism with mk-7 recently and I think that it could be (and there is some evidence for this, but not masses) that it acts particularly to accept electrons from Complex I. Normally CoQ10 would be more efficient, but if there is damage to the mtDNA for Complex I mk-7 could handle the situation better.

Hence if it can act to fix the mitochondria slightly then it will reduce endothelial problems.

It may need CoQ10 to handle complex III, but mk-7 (or another hydrophobic menaquinone mk-n where n>6) to get into the membrane wall.

The underlying question is whether mk-n where n>6 supplementation makes mitochondria more efficient or not. Provisionally I think it does.

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#2

I can’t say I am overly impressed by these results. While in the first year there certainly was attenuation in the CAC score of an increase 15 (treated) vs 28 (placebo), so an almost 50% slower accumulation, yet that is still a pretty significant increase of the CAC score in the treatment group.

But the real story is what happens in the second year - we have a massive jump in the CAC score of 34 (treated) vs 41 (placebo)… dramatically diminished improvement vs placebo of some 15% or so compared to the almost 50% in the first year. That’s an absolutely terrible trend line. First of all, with a powerful drug you would expect the accumulation to slow down further with time as the drug keeps working, so maybe a 15 in the first year, but only 10 in the second and so on, or at the very least, to keep going up at the same yearly rate (15) instead of accelerating wildly - jumping to 34 increase the next year, are you kidding me?! Goes up by more than twice as much?! Sorry, but that’s not how an effective drug works over time, this is abysmal even in absolute terms (34 CAC increase!). Second, and even more damning, the accumulation is almost as much as the placebo 34 vs 41, and the rate of increase is much faster in the mk-7 group going from 15 to 34 vs placebo 28 to 41. Given this rate of accumulation one fears what year 3 would bring, not to mention further out. This is a classic trajectory of an initial bump in beneficial effect that quickly goes away with time. The signature of an ineffective drug. Based on this particular result, I would have zero confidence in the effectiveness of long term supplementation of mk-7 at this dose for the attenuation of CAC scored plaque.

Bottom line, unimpressive results at best. YMMV.

#3

I think mk-7 is quite dose dependant.