Vitamin K as an Endocrine Modulator: Mechanistic Links to Glucose Metabolism and Beyond

Vitamin K (VK), traditionally recognized for its role in coagulation, is increasingly implicated in extrahepatic processes, including glucose metabolism and calcium regulation. Suboptimal VK status is common in the general population and may limit these functions, yet evidence linking VK to glucose metabolism and other endocrine axes remains heterogeneous and incompletely synthesized. This narrative review integrates mechanistic, observational, and interventional evidence to examine the role of VK across the endocrine system, with particular emphasis on glucose metabolism. Mechanistic studies indicate that VK supports pancreatic β-cell function, modulates peripheral insulin sensitivity, and enables proper calcium distribution. Observational studies consistently associate higher VK status with a lower risk of type 2 diabetes, while interventional studies suggest that VK supplementation may improve glucose metabolism, primarily in metabolically impaired populations. In bone and mineral metabolism, VK acts synergistically with calcitriol, with combined supplementation showing more consistent benefits on skeletal outcomes than either vitamin alone. Evidence for VK involvement in other endocrine axes, including reproductive and inflammatory pathways, remains limited and largely mechanistic. Overall, the available evidence supports a context-dependent role for VK in glucose metabolism, influenced by base-line nutritional and metabolic status and outcome selection, as well as a synergistic interaction with calcitriol and parathormone in calcium regulation. Future clinical studies should incorporate baseline VK status stratification, dynamic measures of insulin sensitivity, and adequately powered designs to clarify the therapeutic relevance of VK across endocrine and metabolic outcomes.