Vitamin K, discovered in the 1930s, functions as cofactor for the posttranslational carboxylation of
glutamate residues. Gammacarboxy
glutamic acid (Gla)-residues were first identified in
prothrombin and
coagulation factors in the 1970s; subsequently, extra-hepatic Gla
proteins were described, including
osteocalcin and
matrix Gla protein (MGP). Impairment of the function of
osteocalcin and MGP due to incomplete carboxylation results in an increased risk for developing
osteoporosis and
vascular calcification, respectively, and is an unexpected side effect of treatment with oral
anticoagulants. It is conceivable that other side effects, possible involving growth-arrest-specific gene 6 (Gas6)
protein will be identified in forthcoming years. In healthy individuals, substantial fractions of
osteocalcin and MGP circulate as incompletely carboxylated species, indicating that the majority of these individuals is subclinically
vitamin K-deficient. Potential new application areas for
vitamin K are therefore its use in dietary supplements and functional foods for healthy individuals to prevent bone and
vascular disease, as well as for patients on oral
anticoagulant treatment to offer them protection against
coumarin-induced side effects and to reduce diet-induced fluctuations in their INR values.