The multifunctional role of vitamin K2 in biological systems

Abstract

The increasing prevalence of non-communicable diseases and an aging population are driving interest in micronutrients capable of modulating coordinated metabolic and signaling networks. Vitamin K2 (menaquinones) is traditionally considered a cofactor of γ-glutamyl carboxylase in the vitamin K cycle, which provides γ-carboxylation of vitamin K-dependent proteins. At the same time, recent data indicate broader extrahepatic effects that link the carboxylation status of osteocalcin and matrix Gla protein to bone mineralization and vascular calcification processes, as well as pointing to potential non-carboxylation mechanisms in the regulation of redox balance, inflammation, and cellular metabolism. The aim of the study was to systematize current knowledge on the molecular mechanisms and tissue-specific effects of vitamin K2 (mainly MK-4 and MK-7) in hemostasis, the bone-vessel axis, metabolic-endocrine regulation, immune-inflammatory responses, and neurobiology, identifying gaps in the evidence base for clinical translation. A narrative synthesis with elements of a scoping approach was performed based on a search in PubMed/MEDLINE, Scopus, and Web of Science; priority was given to randomized studies, meta-analyses, and cohort studies supported by in vitro/in vivo mechanistic data. Biomarkers of vitamin K functional status, in particular dp-ucMGP and uncarboxylated osteocalcin, were analyzed separately. Therefore, the effects of K2 are context-dependent and determined by the form of menaquinone, dose, duration, and baseline vitamin K status; MK-7 is characterized by more stable pharmacokinetics and better extrahepatic carboxylation. The heterogeneity of clinical outcomes justifies the need for standardized interventions, biomarker-oriented stratification, and the selection of clinically meaningful endpoints (calcification, fractures) with parallel assessment of redox and inflammatory signaling pathways. Promising avenues include evaluating the neuro- and hero-protective potential of K2 in well-designed studies.