Vitamin K: Metabolism, Genetic Influences, and Chronic Disease Outcomes

ABSTRACT Vitamin K refers to a group of lipid‐soluble vitamins that exist in two natural isoforms; phylloquinone (PK, vitamin K1) and menaquinones (MKs, vitamin K2). Phylloquinone, the primary dietary source, is found abundantly in green vegetables and plant oils. Menaquinones (MK‐4 through MK‐13) are synthesized by anaerobic bacteria and may be obtained through the diet from fermented foods and animal products (e.g., meats, dairy and eggs). Originally recognized for its role in blood coagulation, vitamin K is an essential cofactor for the posttranslational carboxylation of vitamin K‐dependent proteins (VKDPs), which are implicated in various physiological processes including; blood coagulation, calcium homeostasis, as well as metabolic and inflammatory pathways. Therefore, vitamin K has attracted considerable research interest for its potential implications in several diseases. While promising, the specific roles of vitamin K in various health conditions, the quantity of vitamin K (both PK and MKs) required for the function of various VKDPs, and the influence of genetics on vitamin K metabolism, remain unclear. This review aims to (i) provide an overview of the structure, dietary sources, metabolism, and physiological roles of vitamin K, including those relating to; cardiovascular diseases, type 2 diabetes, respiratory conditions, musculoskeletal health and cancer; (ii) discuss the impact of genetic factors on vitamin K status and how such factors modulate the role of vitamin K in the aforementioned chronic diseases; and (iii) outline key directions for future research.