N05036: The interaction of vitamins K and D in bone and vascular health - new functional markers of vitamin K status

Study Duration: September 2001 to February 2004

Contractor: St Thomas's Hospital

The role of vitamin K in bone regulation is now increasingly accepted and may be mediated via several vitamin K dependent proteins including osteocalcin and matrix Gla protein (MGP) which are also regulated by vitamin D. Vitamin K is needed to convert certain glutamate (Glu) residues to gamma-carboxyglutamate (Gla) residues, hence the products are called Gla proteins. Without adequate vitamin K, the core protein is synthesised but is undercarboxylated which affects the functionality of the protein. There is strong evidence of a link between sub-optimal vitamin K status, as indicated by high level of undercarboxylated osteocalcin, and osteoporosis. New evidence has also shown MGP to be a potent inhibitor of calcification and that this role is important in bone regulation.

Vitamins K and D may also be involved in vascular calcification, new evidence shows that atherosclerotic calcification is a highly regulated and active process modulated by vitamin D and parathyroid hormone (PTH). There is evidence that low vitamin D status is associated with aortic calcification and that MGP, including its Gla residues, are essential for the prevention of calcification of the artery. These advances suggest that an impaired status of both vitamins K and D contribute to the pathogenesis of both osteoporosis and vascular calcification.

This project will explore the optimal nutrition of vitamins K and D in elderly women using serum and urine samples collected during N05001, a randomised, four group (placebo, vitamin K, vitamin D with calcium, vitamins K and D with calcium) two-year intervention study. The work is based on up-to-date knowledge that vitamin K dependent proteins, especially osteocalcin and MGP, play important roles by promoting both healthy bones and inhibiting abnormal arterial calcification. Vitamin D also regulates the synthesis of osteocalcin and MGP. This project will pursue the recent evidence of a co-operative benefit of vitamins K and D, recently illustrated by the results of N05001 showing a net reduction of bone mineral loss at the wrist. The researchers intend to utilise state of the art assessments of vitamin K status, with expert collaboration for osteocalcin and MGP measurements. This will be the first study for MGP in any elderly population and the first study using a vitamin K/D intervention.