This 2025 paper analyzed clinical trial subjects’ protocol adherence:

“The VitaK-CAC (vitamin K-coronary artery calcification) trial is a double-blind, randomized, placebo-controlled trial in patients with pre-existent CAC who were treated for two years with either placebo or the vitamin K2-analogue menaquinone-7 (MK-7) [360 mcg daily]. The present analysis of the VitaK-CAC trial assesses degree of adherence to supplementation with MK-7 during the implementation and persistence phases.

We estimated adherence in three different ways: 1) by pill counts, 2) by measuring plasma levels of MK-7, and 3) by measuring plasma levels of dephosphorylated, uncarboxylated matrix Gla-protein (dp-ucMGP), a marker of functional bioactivity of vitamin K.

1. We estimated tablet intake by counting the number of pills participants returned to the laboratory at each follow-up visit. When 20% or less of the prescribed pills were returned, this was considered adequate adherence. Due to inconsistent bottle returns by many participants, reliable pill counts could be obtained for only half of the patients. No difference in evolution of the CAC score was found between patients with an adherence below or above 80%, as determined by pill counts.
2. In patients receiving MK-7, an increase in plasma levels above the upper interquartile range (IQR) observed in the placebo group was taken as evidence of supplementation adherence. When this occurred both at 12 months and at 24 months, this was taken as a robust indicator of good persistence. When patients with persistence throughout the study, as based on the MK-7 levels, were compared to those who were not, the former group showed an attenuated progression of their CAC score.
3. We considered a fall in dp-ucMGP by more than 10% as indicative of a positive effect of MK-7 supplementation and, hence, as a proxy for good adherence. Levels of dp-ucMGP rose significantly in both groups, although to a lesser extent in the group with active treatment. If the reduced rise in dp-ucMGP is considered a proxy for adherence, this suggests approximately 60% adherence in the MK-7 group. In 21 of the 75 patients (28%), the rise in MK-7 was sufficiently great for levels of dp-ucMGP to decrease.

There was no difference in the response of MK-7 levels and in the primary outcome (CAC progression) between patients with or without sufficient adherence. We cannot exclude the possibility that variations in absorption or metabolism have contributed to, or may even be entirely responsible for, the observed swings in MK-7 plasma levels.

None of the three methods that we applied in our study is absolutely reliable to estimate adherence to supplementation with MK-7. Measurement of MK-7 levels provides the best information.”

https://www.explorationpub.com/Journals/em/Article/1001321 “Adherence to dietary supplementation with menaquinone-7, a vitamin K2 analogue”

A paper described the clinical trial itself:

https://journals.lww.com/jhypertension/fulltext/2025/05001/menaquinone_7_slows_down_progression_of_coronary.39.aspx “MENAQUINONE-7 SLOWS DOWN PROGRESSION OF CORONARY ARTERY CALCIFICATION. A RANDOMIZED, PLACEBO-CONTROLLED TRIAL” (not freely available, NCT01002157)

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Always more questions:

1. The registration summary included:

In animal studies, active supplementation of Vitamin K2 caused regression of existing arterial calcification. The aim of this randomized, double-blind, placebo-controlled clinical trial is to investigate whether daily supplementation of Vitamin K2 (Menaquinone-7) to patients with established CAC will lead to a decreased progression-rate of CAC after 24 months of follow-up in comparison to placebo.

Is this trial’s stated goal to decrease CAC progression to the point of an unstated goal of reversing existing arterial calcification?

2. What is the degree of success of this clinical trial? I don’t have access to the clinical trial paper, although I’ve requested a copy of it. Did any of the treatment or placebo group subjects reverse their CAC score over 12 or 24 months?

3. Which if any of the items discussed in Vitamin K2 and your brain were suggested to achieve a goal of reversing existing arterial calcification?

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I’ve taken a higher MK-7 daily dose (600 mcg) over the past few years. I take it with a fat source, and without vitamins A, D3, and E to eliminate the possibility of competition from other fat-soluble vitamins.

I haven’t ever had CAC measured because I’m not particularly concerned about existing arterial calcification. I’ll update this post if needed after one of the trial’s researchers provides a copy of their paper.