Vitamin K status of healthy Japanese women: Age-related vitamin K requirement for γ-carboxylation of osteocalcin

Background: Vitamin K deficiency is associated with low bone mineral density and increased risk of bone fracture. Phylloquinone (K₁) and menaquinone 4 (MK-4) and 7 (MK-7) are generally observed in human plasma; however, data are limited on their circulating concentrations and their associations with bone metabolism or with γ-carboxylation of the osteocalcin molecule. Objectives: The objectives were to measure the circulating concentrations of K₁, MK-4, and MK-7 in women and to ascertain whether each form of vitamin K is significantly associated with bone metabolism. Design: Plasma concentrations of K₁, MK-4, MK-7, undercarboxylated osteocalcin (ucOC; measured by using the new electrochemiluminescence immunoassay), intact osteocalcin (iOC), calcium, and phosphorus; bone-derived alkaline phosphatase activity; and concentrations of urinary creatinine, N-terminal telopeptide, and deoxypyridinoline were measured in healthy women (n = 396). Results: On average, MK-7 and MK-4 were the highest and lowest, respectively, of the 3 vitamers in all age groups. K₁ and MK-7 correlated inversely with ucOC, but associations between nutritional basal concentration of MK-4 and ucOC were not observed. Multiple regression analysis indicated that not only K₁ and MK-7 concentrations but also age were independently correlated with ucOC concentration and the ratio of ucOC to iOC. The plasma K₁ or MK-7 concentration required to minimize the ucOC concentration was highest in the group aged ≥70 y, and it decreased progressively for each of the younger age groups. Conclusions: The definite role of ucOC remains unclear. However, if submaximal γ-carboxylation is related to the prevention of fracture or bone mineral loss, circulating vitamin K concentrations in elderly people should be kept higher than those in young people.