Vitamin K and vascular calcification: from biological plausibility to clinical realism

Vitamin K has long been considered a potentially protective factor against ectopic calcification. This review summarizes the biological rationale and randomized clinical evidence for vitamin K supplementation as an anti-calcification strategy, with particular emphasis on chronic kidney disease. The concept is biologically plausible because vitamin K is required for post-translational γ-carboxylation and activation of matrix Gla protein, a key endogenous inhibitor of vascular and valvular calcification. Patients with chronic kidney disease frequently exhibit functional vitamin K deficiency and accelerated vascular and valvular calcification, providing a strong rationale for intervention trials. Randomized studies have therefore examined whether vitamin K1 or vitamin K2, mainly menaquinone-7, can slow progression of coronary, aortic, or valvular calcification. Overall, the evidence remains mixed. Both vitamin K1 and K2 supplementation consistently improves biochemical markers of vitamin K status. However, this biochemical response has not translated uniformly into attenuation of calcification progression on imaging. Across available randomized trials, vitamin K1 has generated the more consistent, although still heterogeneous, evidence for slowing imaging-based calcification progression, particularly in selected high-risk cohorts and in haemodialysis populations receiving intensive dosing. By contrast, vitamin K2 has not produced reproducible benefits on CT-based vascular or valvular calcification endpoints. Importantly, neither vitamin K1 nor vitamin K2 has demonstrated reductions in major adverse cardiovascular events or mortality. Where clinical events were collected, studies were underpowered and results were neutral. At present, vitamin K supplementation remains pharmacodynamically active but clinically unproven as a strategy to prevent cardiovascular endpoints in chronic kidney disease.