Vitamin K is a collective term for a group of fat-soluble compounds required for proper function, particularly blood clotting (coagulation). The vitamin is named for its role in this process, which prevents uncontrolled bleeding. The history of Vitamin K’s discovery was not a singular event but a series of foundational experiments and chemical differentiations spanning over a decade. This timeline reveals how scientists first recognized a missing nutritional factor and later determined it was a family of chemically related compounds.
Identifying the Anti-Hemorrhagic Factor
The initial discovery of the Vitamin K class began in Denmark in the late 1920s with biochemist Carl Peter Henrik Dam. Dam was studying cholesterol metabolism in chickens using a diet severely depleted of fat-soluble components. After several weeks, the chickens developed severe hemorrhagic symptoms, characterized by bleeding under the skin and in the muscles. Dam attempted to resolve these issues by adding purified cholesterol, but this failed to correct the condition.
Dam concluded that an unrecognized, fat-soluble factor was missing from the diet. He determined this substance was necessary for normal blood coagulation, evidenced by the significantly delayed clotting time in the affected animals. In 1934, he published his findings and named the substance “Koagulations-Vitamin,” or Vitamin K, adopting the letter K from the German spelling of coagulation. Dam’s early work established the physiological existence of this anti-hemorrhagic factor, setting the stage for its chemical identification.
Isolation and Naming of Vitamin K1
Following Dam’s foundational work, the scientific focus shifted to isolating and determining the chemical structure of the coagulation factor. This effort was primarily led by American biochemist Edward Adelbert Doisy and his research team at Saint Louis University School of Medicine. Doisy’s group undertook the task of purifying the active compound from natural sources.
In 1939, Doisy’s team successfully isolated the primary form of the vitamin from alfalfa. They determined its exact chemical structure and named it phylloquinone, now commonly known as Vitamin K1. This was a chemical breakthrough that provided the first structural definition of a Vitamin K molecule. For their respective roles in the discovery of the factor and the determination of its chemical nature, Dam and Doisy were jointly awarded the 1943 Nobel Prize in Physiology or Medicine.
Distinguishing the Menaquinone Series (K2)
The discovery of Vitamin K2 occurred when scientists realized that “Vitamin K” was not a single compound. This key differentiation happened shortly after the isolation of K1, primarily in 1940, by Edward Doisy’s research team. They were studying a substance with similar anti-hemorrhagic activity isolated from putrefied fish meal and bacterial cultures.
Doisy and his colleagues recognized that this bacterially derived substance, while functionally similar to K1, had a slightly different chemical structure, specifically in the length of its side chain. This new compound was chemically distinct and designated Vitamin K2, or menaquinone. This discovery confirmed that Vitamin K was a group of compounds, with K1 primarily found in plants and K2 produced by bacterial synthesis. The menaquinone series is characterized by varying lengths of a repeating isoprenoid side chain, designated MK-4 through MK-13.