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. 2025 Oct 12:410:120540.
doi: 10.1016/j.atherosclerosis.2025.120540. Online ahead of print.

Effects of vitamin K2 and D3 supplementation on epicardial adipose tissue and systemic inflammation: A substudy of the AVADEC trial

Selma Hasific  1 , Emil Johannes Ravn  2 , Lars Melholt Rasmussen  3 , Anna Mejldal  4 , Damini Dey  5 , Niels Erik Frandsen  2 , Jes S Lindholt  6 , Søren Auscher  7 , Jess Lambrechtsen  7 , Susanne Hosbond  8 , Dilek Alan  8 , Grazina Urbonaviciene  9 , Søren Becker  9 , Kristian Altern Øvrehus  2 , Axel Diederichsen  2
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Free article

Effects of vitamin K2 and D3 supplementation on epicardial adipose tissue and systemic inflammation: A substudy of the AVADEC trial

Selma Hasific et al. Atherosclerosis. .
Free article

Abstract

Background and aims: Vitamins K2 and D3 may improve cardiovascular health by modulating inflammation and vascular calcification. Inflammation contributes to atherosclerosis and can be assessed through imaging and systemic biomarkers. This study investigated whether vitamin K2 and D3 supplementation reduces inflammation in epicardial adipose tissue (EAT), including pericoronary adipose tissue (PCAT), and systemic inflammation in elderly men at cardiovascular risk.

Methods: In the Aortic Valve DECalcification (AVADEC) trial, 388 men aged 65-74 received daily vitamin K2 (720 μg) and D3 (25 μg) or placebo for 24 months. EAT inflammation was assessed using non-contrast CT [EAT volume and attenuation] and contrast-enhanced CT [PCAT attenuation]. Systemic inflammation was evaluated via hs-CRP, IL-6, TNF-α, Fetuin-A, and osteopontin (OPN). Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), the inactive form of MGP, served as a proxy for vitamin K2 status.

Results: After 24 months, EAT volume increased in the placebo group (Δ5.66 cm3,95% CI 1.35; 9.98) and non-significantly in the vitamin group (Δ3.44 cm3, 95% CI -0.44; 7.33), with an intergroup difference of -2.22 cm3 (95% CI -8.01; 3.57). EAT attenuation declined similarly (intergroup difference: 0.32 HU, 95% CI -0.23; 0.87). PCAT attenuation remained unchanged. No significant changes were seen in systemic markers, though OPN increased modestly in the vitamin group (Δ25.72 pg/mL, 95% CI 2.40; 49.05). dp-ucMGP decreased significantly with supplementation (intergroup difference: 255.31 pmol/L, 95% CI -289.56; -221.05).

Conclusions: Despite reduction in dp-ucMGP, high-dose vitamin K2 and D3 supplementation did not affect EAT, PCAT or systemic inflammation over 24 months. Alternative strategies may be needed to target inflammatory pathways in cardiovascular disease prevention.

Keywords: Atherosclerosis; Cardiac CT scan; Inflammation; Vitamin D3; Vitamin K2.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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