Vitamin K status of healthy Japanese women: age-related vitamin K requirement for gamma-carboxylation of osteocalcin

Am J Clin Nutr. 2006 Feb;83(2):380-6. doi: 10.1093/ajcn/83.2.380.


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 gamma-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 > or =70 y, and it decreased progressively for each of the younger age groups.

Conclusions: The definite role of ucOC remains unclear. However, if submaximal gamma-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Aging / physiology
  • Biomarkers / blood
  • Bone Density / physiology*
  • Bone and Bones / metabolism*
  • Carboxylic Acids / metabolism
  • Female
  • Fractures, Bone / epidemiology
  • Fractures, Bone / etiology
  • Humans
  • Japan
  • Middle Aged
  • Nutritional Requirements
  • Nutritional Status*
  • Osteocalcin / metabolism*
  • Risk Factors
  • Vitamin K / blood*
  • Vitamin K / metabolism
  • Vitamin K 1 / blood
  • Vitamin K 2 / analogs & derivatives
  • Vitamin K 2 / blood
  • Vitamin K Deficiency / complications
  • Vitamins / blood


  • Biomarkers
  • Carboxylic Acids
  • Vitamins
  • Osteocalcin
  • Vitamin K 2
  • Vitamin K
  • menatetrenone
  • Vitamin K 1
  • menaquinone 7