Vitamin K Functions and Functional Markers

Summary

The role of vitamin K extends well beyond the regulation of blood clotting to impact bone formation, and development of heart disease, and possibly cancer.

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The role of vitamin K extends well beyond the regulation of blood clotting to impact bone formation, and development of heart disease, and possibly cancer. The common denominator among these diverse roles is calcium. Vitamin K is required for the carboxylation of glutamate residues on specific proteins to form gamma-carboxyglutamate residues (abbreviated Gla-residues). Proteins that undergo this reaction are called Gla proteins. They either directly bind Ca++ or direct Ca++-dependent interactions with negatively charged surfaces.¹ Thus, vitamin K is critical for bone formation, soft-tissue calcification, cell growth and apoptosis. It has emerged as a potential protector against osteoporosis, atherosclerosis, insulin sensitivity, and cancer.^2-6 In human studies the intake of vitamin K has been associated with a lower risk of coronary calcification and in animal studies vitamin K has reversed arterial calcification.^{2, 7, 8} Vitamin K levels are used as diagnostic and therapeutic parameters in osteoporosis.³ Recommendations for vitamin K intake were originally made on the basis of hepatic requirements for blood coagulation factors.⁷ Accumulating evidence suggests that the requirements to maintain optimal bone and vessel function require higher vitamin K levels.^{6, 9} There are two natural forms of vitamin K which differ based on their phytyl group: phylloquinone (vitamin K1) synthesized in plants, and menaquinone (vitamin K2) produced by bacteria in the gut. Both forms have been used to assess vitamin K status via direct measurement in serum, though such direct measurements are generally not accepted as a reliable index of vitamin K status.^{7, 8} Functional markers provide a more accurate assessment of vitamin K status, they include prothrombin time, undercarboxylated prothrombin (PIVKA-II), and undercarboxylated osteocalcin. A vitamin K deficiency can lead to impairment in the carboxylation of osteocalcin, resulting in an increase in the undercarboxylated form in circulation, where it can be measured to identify vitamin K status.