Vitamin K2/MK-7 Slows Calcification in Heart Arteries: Does it Matter?

At the KAHN CENTER, we perform the most accurate assessments of vascular disease and then apply strategies to slow and reverse atherosclerosis. One of the tools available is a vitamin called K2/MK-7.  There is also a similar one called K2/MK-4 and many supplements have both. 

Vitamin K2 supplementation can reduce the progression of vascular calcification in patients with diabetes or end-stage kidney disease. Presently, it is unknown whether vitamin K2 is also beneficial in patients with symptomatic atherosclerotic coronary artery disease (CAD) who do not have those conditions. A new study has reported important findings to know. 

STUDY

The study was planned to evaluate whether supplementation with the vitamin K2 homologue menaquinone-7 (MK-7) for a period of 2 years attenuates the progression of coronary artery calcification (CAC) compared with placebo.

The study was a 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.

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

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. 

RESULTS

Altogether, 180 patients could be randomized (90 patients per group), with 85 patients receiving MK-7 (median age 59, 36 [42%] female) and 82 receiving placebo (median age, 61 years; 34 [42%] female). Baseline characteristics were comparable for the 2 groups.

Plasma levels of MK-7 rose significantly in the active treatment group.

In the placebo group, CAC scores increased from a median 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.

No significant adverse effects were observed.

At baseline, all patients had visible coronary plaques on coronary CT angiograpy. In mostcases this caused mild stenosis. None of the patients had a highrisk plaque. Overall, stenosis severity increased among 31 of 75 patients receiving placebo (41%) and 25 of 75 patients receiving MK-7 (33%) (difference not significant).

Progression in the number of affected vessels did not differ between the groups either.
All 3 plaque categories (noncalcified, partially calcified, and calcified) increased significantly in all segments but without significant differences between the 2 groups. Increases in CAC score correlated significantly with the number of noncalcified plaques that became partially calcified during the study but not with any of the other types of plaque.

CONCLUSIONS

The findings of this study suggest that moderate dose supplementation with Vitamin K2 as 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 as the study was not big enough or long enough to measure clinical events like heart attacks or hospitalizations.

Should we add vitamin K2/MK-7 to all patients with an elevated calcium score and plaque? This remains unknown despite this study. It remains to be seen if slowing the rate of calcifications, particularly in the non-calcified plaque, results in clinical benefit, is neutral, or is even harmful as non-calcified plaque may be of more risk for clinical events.

There also versions of vitamin K2 available with mixtures of MK-4 and MK-7 with over 50 times higher doses than used in this study. The impact of those preparations on heart outcomes is also unknown.  

At the KAHN CENTER, we will continue to use vitamin K2 in our vitamin D3 preparations (usually around 180 ug dose of Mk-7) and will use the higher dose version in some patients but more data is needed.