The discovery of vitamin K and its clinical applications.

Vitamin K was discovered fortuitously in 1929 as part of experiments on sterol metabolism and was immediately associated with blood coagulation. In the decade that followed, the principal K vitamers, phylloquinone and the menaquinones, were isolated and fully characterized. In the early 1940s, the first vitamin K antagonists were discovered and crystallized with one of its derivatives, warfarin, still being widely used in today's clinical setting. However, major progress in our understanding of the mechanisms of action of vitamin K came in the 1970s with the discovery of γ-carboxyglutamic acid (Gla), a new amino acid common to all vitamin K proteins. This discovery not only provided the basis to understanding earlier findings about prothrombin but later led to the discovery of vitamin K-dependent proteins (VKDPs) not involved in hemostasis. The 1970s also saw an important breakthrough with respect to our understanding of the vitamin K cycle and marked the discovery of the first bone VKDP, osteocalcin. Important studies relating to the role of vitamin K in sphingolipid synthesis were also underway at that time and would pave the way to further work 15 years later. The decades that followed saw the discovery of additional VKDPs showing wide tissue distribution and functional scope, the latest members having been identified in 2008. The 1990s and 2000s were also marked by important epidemiological and intervention studies that focused on the translational impact of recent vitamin K discoveries, notably with respect to bone and cardiovascular health. This short review presents an overview of the history of vitamin K and of its recent developments.