Evidence Trace, complete trial record

In plain terms

In plain terms: Vitamin K2 (MK-7 / Menaquinone-7) shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.

Vitamin K2 (MK-7 / Menaquinone-7)

C Limited: small, mixed or unreplicated trials

Category Supplements

Evidence Randomized controlled trial (3-year, arterial stiffness)

Reviewed July 2026

PMIDs 25694037 · 15514282 · 42268593 · 32817311 · 26892582 · 33068157

The endpoint this grade is based on: Surrogate biomarker endpoint, Carboxylates matrix Gla protein (MGP), a protein involved in inhibiting vascular and soft-tissue calcification; supports bone density through osteocalcin carboxylation. Cardiovascular event prevention has not been established.

The evidence as the record states it

Evidence record

PMID 25694037 PMID 15514282 PMID 42268593 PMID 32817311 PMID 26892582 PMID 33068157

Knapen et al. (Thrombosis and Haemostasis, 2015; PMID 25694037): 3-year RCT showing MK-7 180 mcg/day reduced arterial stiffness and improved arterial flexibility. Rotterdam Study (Geleijnse et al.): observational: higher dietary K2 associated with lower cardiovascular mortality. Geleijnse et al. (J Nutr, 2004; PMID 15514282) is the Rotterdam dietary-menaquinone cohort, observational and not grade-bearing. Vossen et al., VitaK-CAC (JAMA Cardiology, 2026; PMID 42268593): 2-year randomized placebo-controlled trial of MK-7 360 mcg/day in 180 patients with symptomatic coronary artery disease and a baseline CAC score of 50 to 400 Agatston units. Plasma MK-7 rose in the treated arm and the authors report slowed calcification in noncalcified plaque, stating that the clinical significance in terms of plaque stability remains to be determined. Coronary artery calcification is a surrogate, not a cardiovascular event. Other randomized trials of vitamin K2 on arterial stiffness or calcification were null (Witham et al., J Am Soc Nephrol, 2020; PMID 32817311; Fulton et al., J Nutr Health Aging, 2016; PMID 26892582; Bartstra et al., Eur J Nutr, 2021; PMID 33068157). Grade C: mixed trials on markers that are not established stand-ins.

PMID 25694037 PMID 15514282 PMID 42268593 PMID 32817311 PMID 26892582 PMID 33068157

Why Grade C and not Grade B

Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.

What this grade covers and what it does not

Grade C. Some randomized trials of MK-7 slowed arterial stiffening or coronary calcification (Knapen et al., Thromb Haemost, 2015; PMID 25694037; Vossen et al., JAMA Cardiol, 2026; PMID 42268593), and others found no effect on stiffness or calcification (Witham et al., J Am Soc Nephrol, 2020; PMID 32817311; Fulton et al., J Nutr Health Aging, 2016; PMID 26892582; Bartstra et al., Eur J Nutr, 2021; PMID 33068157). Arterial stiffness and coronary calcium are not established stand-ins for a clinical outcome under the B definition, and the trials are mixed: C. WHAT THIS GRADE DOES NOT COVER: heart attack, stroke or death, which no trial of vitamin K2 has measured; and bone outcomes.

What would move this grade

A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.

How to track whether this is working For MK-7, dp-ucMGP is a pharmacodynamic marker of vitamin K status/carboxylation and arterial stiffness can be followed when that is the indication. DEXA is appropriate for long-term bone outcomes. Do not treat dp-ucMGP or undercarboxylated osteocalcin as proven surrogates for fracture or cardiovascular-event reduction.