Key result
Vitamin K2 plus D3 slows CAC progression by ~21% vs placebo over 24 months.
Why the study?
Coronary artery calcification progression strongly predicts cardiovascular events, but whether vitamin K2 and D3 supplementation reduces progression in severe calcification was unknown.
Does vitamin K2 and D3 supplementation reduce coronary artery calcification progression in patients with severe coronary artery calcification?
RCT (n=398)
Double-blind
Randomized
Yes
Does vitamin K2 and D3 supplementation reduce coronary artery calcification progression in patients with severe coronary artery calcification?
Mean Difference: -52 (95% CI -79–-24)
Absolute Event Rate: 196% vs 248%
Supplementation with high-dose vitamin K2 and D3 significantly attenuated the progression of coronary artery calcification over 24 months in patients with severe baseline calcification.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The DANCODE trial was well-done and powered sufficiently, with low risk for bias. The results were robust, consistent across subgroups, and consistent with prior work. It appears that vitamin K2-D3 is an effective agent to slow CAC progression.”
“However, we do not know if vitamin K2-D3 is effective for the prevention of clinical events.”
“In 398 adults who already had severe coronary calcification, two years of vitamin K2 plus vitamin D3 slowed the growth of their calcium score by 52 Agatston units, about 21 percent less progression than placebo, and did it without pushing plaque into the softer, rupture-prone form. That is a real, well-designed finding with a modest effect size and no outcome data behind it yet.”
Vitamin K2 plus D3 slowed CAC progression in severe disease; leaves open clinical event reduction and routine use pending larger trials.
BACKGROUND: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular events. We investigated whether supplementation with vitamin K 2 and vitamin D 3 reduces CAC progression in patients with severe coronary calcification. METHODS: In this multicenter, double-blind, placebo-controlled randomized trial, 400 participants with a CAC score ≥400 Agatston units (AU) were randomly assigned to vitamin K 2 (720 μg/d) plus vitamin D 3 (25 μg/d) or placebo for 24 months. Participants were enrolled from February 2023 to February 2024. Noncontrast cardiac computed tomography was performed at baseline, 12 months, and 24 months. The primary end point was change in CAC score at 24 months. Subgroup analyses by sex and baseline CAC subgroups (400–999 and ≥1000 AU) were performed. Change in plaque composition was assessed in a subset with CAC score <1000 AU who underwent coronary computed tomography angiography at baseline and 24 months. RESULTS: A total of 398 participants (30% women; median age, 71 years) were included. Median baseline CAC was 903 AU, and 44% had CAC ≥1000 AU. In the intention-to-treat analysis, the mean CAC increase was 196 AU (95% CI, 178–214) with vitamin K 2 and D 3 and 248 AU (95% CI, 225–271 AU) with placebo (between-group difference, −52 AU [95% CI, −79 to −24]). The treatment effect was consistent across sex and baseline CAC subgroups. In the 143 participants who underwent coronary computed tomography angiography, there were a similar increase in total plaque volume and no change in noncalcified plaque volume between groups; progression of calcified plaque volume was attenuated in the intervention group (between-group difference, −8 mm 3 [95% CI, −13 to −2]). CONCLUSIONS: Among patients with severe CAC, supplementation with vitamin K 2 and vitamin D 3 reduced progression of CAC over 24 months. The reduction in calcification progression was not associated with an increase in noncalcified plaque volume. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05500443.
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A 2026 study conducted an RCT in Severe Coronary Artery Calcification (n=398). Vitamin K2 and Vitamin D3 vs. Placebo was evaluated on Change in CAC score at 24 months (MD -52, 95% CI -79 to -24). Supplementation with vitamin K2 and vitamin D3 reduced coronary artery calcification progression over 24 months compared to placebo (mean difference, -52 AU; 95% CI, -79 to -24).
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