Vitamin K1 (phylloquinone) and vitamin K2 (menaquinones), differ regarding food source (green vegetables and fermented products, respectively), bioavailability and intermediate metabolism.
As a cofactor for carboxylase activity, vitamin K can facilitate the conversion of glutamyl to gamma-carboxyglutamyl residues and influence the synthesis and excretion of gamma-carboxylation of osteocalcin to increase the formation of bone.
There is a closely relationship between vitamin K and osteoporosis. In the past decade it has become evident that vitamin K has a significant role to play in human health that is beyond its well-established function in blood clotting.
There is evidence in human intervention studies that vitamins K and D, a classic in bone metabolism, works synergistically on bone density. Most of these studies employed vitamin K(2) at rather high doses, a fact that has been criticized as a shortcoming of these studies. However, there is emerging evidence in human intervention studies that vitamin K(1) at a much lower dose may also benefit bone health, in particular when coadministered with vitamin D. Several mechanisms are suggested by which vitamin K can modulate bone metabolism. Besides the gamma-carboxylation of osteocalcin, a protein believed to be involved in bone mineralization, there is increasing evidence that vitamin K also positively affects calcium balance, a key mineral in bone metabolism. The Institute of Medicine recently has increased the dietary reference intakes of vitamin K to 90 microg/d for females and 120 microg/d for males, which is an increase of approximately 50% from previous recommendations.
There is a wealth of epidemiologic studies investigating the association of vitamin K status and various markers of bone health including clinical endpoints such as BMD and fracture rate.
Patients with osteoporosis who had sustained an acute fracture (hip fracture) or suffered from a chronic fracture (spinal crush fracture) had lower circulating vitamin K1 serum levels than control subjects. Vitamin K intakes of individuals in the lowest decile of bone density were significantly lower than those of individuals in the highest decile
There is a consistent line of evidence in human epidemiologic and intervention studies that clearly demonstrates that vitamin K can improve bone health.
The first human intervention study investigating the effect of vitamin K on markers of bone strength such as BMD was published 10 y ago. In a small study comprising 17 patients on hemodialysis with low-turnover bone disease, supplementation with vitamin K2 (45 mg/d for 12 mo) prevented loss of bone density.
Vitamin K antagonists and bone health
Because the commonly prescribed oral anticoagulants are vitamin K antagonists, studies of patients taking those drugs have investigated the effect of vitamin K on bone status. Several such studies have been conducted, with mixed results. Some studies found no relation between the use of a vitamin K antagonists and bone status, whereas other studies did.
The occurrence of warfarin embryopathy (severe bone defects in offspring born to women who received warfarin during pregnancy)clearly demonstrated that warfarin has an adverse effect on developing bone, but the effects of coumarin-based anticoagulant therapy on the structural and functional integrity of adult bone are much less clear. Whether or not anticoagulants affect fracture risk appears to be in part dependent on the duration of anticoagulant use.
Dietary vitamin K variability affects International Normalized Ratio (INR) coagulation indices.
Changes in daily vitamin K intake may contribute to marked variations in the International Normalized Ratio (INR) coagulation index in patients receiving oral warfarin anticoagulant therapy, with potentially serious adverse outcomes.
prospective dietary assessment study was conducted at the Massachusetts General Hospital in Boston. Sixty outpatients (37 males and 23 females) were selected with a mean age 60.3 +/- 16.8 years, who began oral warfarin anticoagulant therapy within 14 days prior to their first clinic visit to an outpatient anticoagulation therapy unit. Week-to-week changes in vitamin K intake, warfarin dose, and INR were determined and cross-correlated.
correlation coefficient revealed the variability in INR and changes in vitamin K intake were inversely correlated (r = -0.600, p < 0.01). Multiple regression analysis (r = 0.848) indicated that a weekly change of 714 mug dietary vitamin K significantly altered weekly INR by 1 unit (p < 0.01) and a weekly change of 14.5 mg warfarin significantly altered weekly INR by 1 unit (p < 0.01) after adjustment for age, sex, weight, height, and concomitant use of medications known to interact with warfarin.
Patients taking warfarin and consuming markedly changing amounts of vitamin K may have a variable weekly INR with potentially unstable anticoagulant outcomes.