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. 2023 Nov 24;2(9):100643.
doi: 10.1016/j.jacadv.2023.100643. eCollection 2023 Nov.

Effects of Vitamin K2 and D Supplementation on Coronary Artery Disease in Men: A RCT

Selma Hasific  1 , Kristian A Oevrehus  1 , Jes S Lindholt  2 , Anna Mejldal  3 , Damini Dey  4 , Jordi S Dahl  1 , Niels Erik Frandsen  1 , Søren Auscher  5 , Jess Lambrechtsen  5 , Susanne Hosbond  6 , Dilek Alan  6 , Grazina Urbonaviciene  7 , Søren Becker  7 , Lars M Rasmussen  8 , Axel P Diederichsen  1
Affiliations

Effects of Vitamin K2 and D Supplementation on Coronary Artery Disease in Men: A RCT

Selma Hasific et al. JACC Adv. .

Abstract

Background: Extent and progression of coronary artery calcification (CAC) are strong predictors of myocardial infarction and mortality.

Objectives: This study aims to investigate if vitamin K2 and D supplementation can reduce CAC progression.

Methods: A total of 389 participants were randomized to supplementation with vitamin K2 (720 μg/day) and D (25 μg/day) vs placebo in a multicenter double-blinded randomized controlled trial. The primary endpoint (progression of aortic valve calcification) has been reported. This study reports CAC progression in participants with no ischemic heart disease. CT scans were performed at baseline, 12, and 24 months. ΔCAC and coronary plaque volume were evaluated in the entire group and in 2 subgroups. A safety endpoint was the composite of myocardial infarction, coronary revascularization, and all-cause mortality.

Results: In total, 304 participants (male, mean age 71 years) were identified. The intervention and placebo group both increased in mean CAC scores from baseline to 24-month follow-up (Δ203 vs Δ254 AU, P = 0.089). In patients with CAC scores ≥400 AU, CAC progression was lower by intervention (Δ288 vs Δ380 AU, P = 0.047). Plaque analyses showed no significant difference in progression of noncalcified plaque volume (Δ-6 vs Δ46 mm3, P = 0.172). Safety events were fewer in participants receiving supplementation (1.9% vs 6.7%, P = 0.048).

Conclusions: Patients with no prior ischemic heart disease randomized to vitamin K2 and D supplementation had no significant reduction in mean CAC progression over a 2-year follow-up compared to placebo. Although the primary endpoint is neutral, differential responses to supplementation in those with CAC scores ≥400 AU and in safety endpoints are hypothesis-generating for future studies.

Keywords: CAC score; cardiac CT scan; coronary artery disease; vitamin D; vitamin K2.

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Conflict of interest statement

Study execution was supported by unrestricted grants from the 10.13039/100007405Danish Heart Foundation (grant No. 17-R116-A7569-22071), the Region of Southern Denmark’s Research Council (grant No. 17/15638), and the 10.13039/501100009708Novo Nordisk Foundation (grant No. NNF17OC0029076). Salary for the investigator Dr Hasific was supported by grants from the Danish Cardiovascular Academy funded by the 10.13039/501100009708Novo Nordisk Foundation (grant No. NNF20SA0067242), the 10.13039/100007405Danish Heart Association, and the Region of Southern Denmark’s Research Council. The study tablets, including placebo, were provided free of charge by Kappa Bioscience, Norway, and Orkla Care, Denmark. The funders had no influence on the design or conduct of the trial and were not involved in data collection or analysis, in the writing of the article, or in the decision to submit for publication. Dr Diederichsen has served as an expert on a Generally Recognized as Safe panel to review the safety of vitamin K2 and its proposed use in foods in the United States. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Enrollmentand Randomization of Patients
Figure 2
Figure 2
CAC Score Progression According to Treatment Allocation Showing no significant difference in CAC score progression in the total population as well as in participants with baseline CAC score <400 AU. However, in the subgroup of participants with baseline CAC score above 400 AU, a significant difference at 24-month follow-up is shown (P = 0.047).
Figure 3
Figure 3
Forest Plot of Stratified Analyses of CAC Score Progression in the Total Population Showing significant reduction of CAC score progression in participants with statin therapy.
Figure 4
Figure 4
Plaque Volume Progression According to Treatment Allocation Showing no significant difference in 24-month progression of plaque volumes including calcified and noncalcified plaque.
Central Illustration
Central Illustration
The Effect of Vitamin K2and D vs Placebo on Change in CAC Score and Plaque Volumes Over a 2-Year Follow-Up Period CAC = coronary artery calcification; CT = computed tomography.
See this image and copyright information in PMC

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