Vitamin K in the Treatment and Prevention of Osteoporosis and Arterial Calcification

Jamie Adams; Joseph Pepping

Disclosures

Am J Health Syst Pharm. 2005;62(15):1574-1581. 

In This Article

Vitamin K

Vitamin K refers to a group of related compounds. There are two natural forms: phylloquinone (vitamin K1) and menaquinone (vitamin K2). Phylloquinone is the most common form of vitamin K and is found in leafy green vegetables (e.g., lettuce, broccoli, spinach, cabbage) and vegetable oils (e.g., soybean and canola oils). Commercially prepared vitamin K1 (phytonadione) is chemically identical to naturally occurring vitamin K1 (phylloquinone).

Menaquinone includes a range of related forms generally designated as menaquinone-n (MK-n), where n is the number of isoprenyl groups. Menaquinone is found in meat, fermented products, and cheese. The menaquinones most commonly found in food are MK-4, which is a short-chain menaquinone, and the long-chain menaquinones MK-7, MK-8, and MK-9.[20] Intestinal bacteria also produce the longer-chain menaquinones (MK-7-MK-10);[21] however, bacteria-derived menaquinone appears to contribute minimally to overall vitamin K status.[1,22,23] Menaquinone, in the form of MK-4 (also known as menatetrenone), has been used in Japan for the treatment of osteoporosis since 1995. Dietary supplements containing up to 15 mg of menaquinone (MK-4) per capsule have recently become available in the United States.

In humans, vitamin K is primarily a cofactor in the enzymatic reaction that converts glutamate residues into γ-carboxyglutamate residues in VKD proteins.[21,24,25,26,27,28] Vitamin K deficiency can lead to suboptimal γ-carboxylation of these proteins and impairment of their function.[29,30,31,32] These VKD proteins are involved in such functions as coagulation-factor activation (factors V, VII, and X; prothrombin; and fibrinogen), bone metabolism, and inhibition of vascular calcification. The vitamin K requirement for carboxylation of bone and arterial wall VKD proteins is higher than that for the carboxylation of coagulation factors in the liver.[33] Daily vitamin K requirements for maximal γ-carboxylation of the extrahepatic VKD proteins may be significantly higher than recommended by current dietary guidelines.[33] Vitamin K deficiency, resulting in the undercarboxylation of specific VKD proteins, may be an independent risk factor for osteoporosis and arterial calcification.

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