Does menaquinone-7 (MK-7) supplementation, combined with vitamin D, reduce the progression rate of aortic valve calcification (AVC) in men with aortic stenosis?
Vitamin K2, a randomized trial in 365 men (Circulation 2022, PMID 35465686) — two years of MK-7 and vitamin D supplementation did not slow aortic valve calcification progression in elderly men, despite improving a biomarker of vitamin K status. The rates of heart valve surgery (1 vs 2 patients), all-cause death (1 vs 4 patients), and cardiovascular events (10 vs 10 patients) were also not significantly different.
Source: Circulation 2022, PMID 35465686 ↗ · Research map · How Magellan grades evidence · evidence confidence: high
Circulation · 2022 · PMID 35465686 · DOI 10.1161/CIRCULATIONAHA.121.057008
Two years of MK-7 and vitamin D supplementation did not slow aortic valve calcification progression in elderly men, despite improving a biomarker of vitamin K status.
The question
Does menaquinone-7 (MK-7) supplementation, combined with vitamin D, reduce the progression rate of aortic valve calcification (AVC) in men with aortic stenosis?
What they tested
Menaquinone-7 (MK-7), a cofactor for carboxylation of proteins inhibiting arterial calcification, may reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis.
How they did it
This was a randomized, double-blind, multicenter trial involving 365 men from the community with an AVC score >300 arbitrary units (AU). Participants were randomized to receive daily treatment with 720 µg MK-7 plus 25 µg vitamin D or a matching placebo for 24 months. The primary outcome was the change in AVC score, with secondary outcomes including changes in aortic valve area, peak aortic jet velocity, heart valve surgery, aortic and coronary artery calcification, and dp-ucMGP levels. Safety outcomes included all-cause death and cardiovascular events.
What they found
The mean increase in AVC score was 275 AU in the intervention group and 292 AU in the placebo group, with a mean difference of 17 AU. There were no significant differences between groups in changes in aortic valve area, peak aortic jet velocity, or progression of aortic and coronary artery calcification. The rates of heart valve surgery (1 vs 2 patients), all-cause death (1 vs 4 patients), and cardiovascular events (10 vs 10 patients) were also not significantly different. However, a significant reduction in dp-ucMGP was observed in the MK-7 plus vitamin D group (-212 pmol/L) compared to the placebo group (45 pmol/L).
| MK-7 + Vitamin D | 275 | |
|---|---|---|
| Placebo | 292 |
The mean increase in AVC score was 275 AU in the intervention group and 292 AU in the placebo group over 24 months.
What it means
In elderly men with an AVC score >300 AU, 2 years of MK-7 plus vitamin D supplementation did not influence the progression of aortic valve calcification, despite a significant reduction in dp-ucMGP.
Limitations
The study was conducted on elderly men from the community with a specific AVC score, which may limit generalizability to other populations or those with different stages of aortic stenosis.
The paper at a glance
| Magellan’s evidence label | matrix Gla-protein carboxylation (our label for this citation — see PubMed for the paper’s own title and authors) |
|---|---|
| Journal | Circulation |
| Year | 2022 |
| PMID | 35465686 ↗ |
| DOI | 10.1161/CIRCULATIONAHA.121.057008 ↗ |
| Topic | Nutrition, micronutrients & whole foods |
Read the source: PubMed record (authors, abstract, full citation) ↗ · Publisher via doi.org ↗
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Vitamin K2 (MK-7)
In humans, MK-7 supplementation consistently improves vitamin K-status biomarkers — lowering circulating dephospho-uncarboxylated MGP by about half and markedly reducing undercarboxylated osteocalcin — and one well-run three-year randomized trial in healthy postmenopausal women found modestly improved arterial…
Vitamin K2 (menaquinone) is a fat-soluble vitamin obtained from fermented foods such as natto and some…
Research describes the compound or intervention studied. It is not a claim about any specific product.
Molecules & mechanisms in this paper
Each of these is named in the paper’s own words above. Open the monograph for the full mechanism and its other citations.
Cite this page
These citations point at this summary. To cite the original paper with its full author list, use the PubMed record or doi.org.
Magellan Longevity. (2026). Does menaquinone-7 (MK-7) supplementation, combined with vitamin D, reduce the progression rate of aortic valve calcification (AVC) in men with aortic stenosis? [Plain-English summary of Circulation 2022, PMID 35465686, DOI 10.1161/CIRCULATIONAHA.121.057008]. Magellan Longevity. https://magellanlongevity.com/study/s138.html@misc{magellan_s138,
title = {Does menaquinone-7 (MK-7) supplementation, combined with vitamin D, reduce the progression rate of aortic valve calcification (AVC) in men with aortic stenosis?},
author = {{Magellan Longevity}},
year = {2026},
howpublished = {\url{https://magellanlongevity.com/study/s138.html}},
note = {Plain-English summary of PubMed PMID 35465686; DOI 10.1161/CIRCULATIONAHA.121.057008; Circulation 2022. Reviewed by Gabriel Radu, DO},
urldate = {2026-08-11}
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