---
title: "Evidence: matrix Gla-protein carboxylation"
description: "Two years of MK-7 and vitamin D supplementation did not slow aortic valve calcification progression in elderly men, despite improving a biomarker of…"
url: "https://magellanlongevity.com/study/s138.md"
canonical: "https://magellanlongevity.com/study/s138.html"
html: "https://magellanlongevity.com/study/s138.html"
type: "study"
study_key: "s138"
journal: "Circulation"
year: 2022
pmid: "35465686"
doi: "10.1161/CIRCULATIONAHA.121.057008"
citations: 1
updated: 2026-09-02
author: "Gabriel Radu, DO"
author_credentials: "Physiatrist (PM&R). NY medical license 275110. NPI 1376861765."
publisher: "Magellan Longevity"
content_format: "markdown"
---

# Evidence: matrix Gla-protein carboxylation

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## Citation

| Field | Value |
| --- | --- |
| Journal | Circulation |
| Year | 2022 |
| PMID | [35465686](https://pubmed.ncbi.nlm.nih.gov/35465686/) |
| DOI | [10.1161/CIRCULATIONAHA.121.057008](https://doi.org/10.1161/CIRCULATIONAHA.121.057008) |
| Study key | s138 |

## Takeaway

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?

## Hypothesis

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.

## Methods

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.

## Results

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).

## Conclusion

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.

## Verbatim from the abstract

> a cofactor for the carboxylation of proteins involved in inhibition of arterial calcification

## Mean Change in AVC Score Over 24 Months

| Measure | Mean Increase in AVC Score (AU) |
| --- | --- |
| 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.*

## Where this study is used on Magellan

This paper is one of the citations behind the evidence grade on the pages below. Grades are assigned from the published research and are independent of affiliate commissions.

| Compound or device | Evidence grade | Graded pages |
| --- | --- | --- |
| Vitamin K2 (MK-7) | Moderate evidence | [Vitamin K2 (MK-7)](https://magellanlongevity.com/p/138.md) |

## Reference

1. **Evidence: matrix Gla-protein carboxylation**
   Circulation 2022 · [PMID 35465686](https://pubmed.ncbi.nlm.nih.gov/35465686/) · [DOI 10.1161/CIRCULATIONAHA.121.057008](https://doi.org/10.1161/CIRCULATIONAHA.121.057008)

   > a cofactor for the carboxylation of proteins involved in inhibition of arterial calcification

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## Related on Magellan Longevity

- [Vitamin K2 (MK-7)](https://magellanlongevity.com/p/138.md) — product graded on this and related evidence
- [The effect of menaquinone-7 supplementation on vascular calcification in patients with…](https://magellanlongevity.com/study/d31387121.md)
- [Effect of vitamin K supplementation on arterial stiffness in vitamin K-deficient kidney…](https://magellanlongevity.com/study/d36695702.md)
- [Longevity research map](https://magellanlongevity.com/longevity-research-map.html)
- [Evidence-based longevity supplements](https://magellanlongevity.com/longevity-supplements.md)

## Scope and disclosures

Educational information, not medical advice. Nothing here is intended to diagnose, treat, cure, or prevent any disease. Talk to your physician before starting any supplement or device, especially if you are pregnant, nursing, or taking medication.

Editorial firewall: evidence grades are assigned from the published research and are independent of any affiliate commission. As an Amazon Associate, Magellan Longevity earns from qualifying purchases.

Reviewed for accuracy by a board-certified physician (DO).