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LE Magazine April 2006

Vitamin K's Delicate Balancing Act

By Julius G. Goepp, MD

Other Effects of Vitamin K Antagonists

Supporting active vitamin K-dependent Gla-proteins in patients on warfarin is also a good idea in light of what we have learned about the importance of these proteins in tissues besides blood. Because warfarin inhibits activation of Gla-proteins, it has the potential to reverse vitamin K’s effects, causing reduced calcification of bone and increased calcification of blood vessels. Both laboratory and clinical evidence support this suspicion.42 Warfarin blocked vitamin D-induced production of the bone protein osteocalcin in a laboratory model;69 subsequently, doses of warfarin comparable to those used in humans reduced bone strength and volume in laboratory rats.70 Reduced bone mineral density has been observed in warfarin-treated patients,71 and an association between the chronic use of warfarin and fracture risk has been reported in humans.72,73 A recent study of children on long-term warfarin therapy found significantly lower bone mineral density in the lumbar spine of treated patients than in a group of randomly selected controls.74


Topical application of vitamin K may help speed the healing of bruises, according to a study from the University of Miami School of Medicine.77 Cosmetic procedures such as pulsed dye laser treatment often result in significant bruising. The Miami team investigated whether topical vitamin K could help prevent or clear bruising induced by laser treatment.

Twenty-two patients were enrolled in this randomized, double-blind, placebo-controlled trial. Eleven participants applied vitamin K cream to half of the face and a similar cream containing no vitamin K to the other half of the face for two weeks prior to laser treatment. The other 11 subjects followed the same procedure each day for two weeks following the laser procedure.

The side of the face treated with topical vitamin K prior to laser treatment showed no significant difference in bruising compared to placebo. However, the side of the face treated with vitamin K after treatment demonstrated significantly lower scores of bruising compared to the placebo-treated side.77

While pre-treatment with vitamin K cream does not appear to prevent bruising, application of vitamin K cream following laser treatment may help reduce the severity of bruising, particularly in the initial days of application.77

Arterial calcification, which is prevented by vitamin K-dependent matrix proteins, might also be influenced by warfarin treatment.14 Arterial calcification has been produced experimentally in rats by treatment with warfarin.40,41 In a 2005 study of older patients with known calcification of the aortic valve, those who had been on long-term oral anticoagulation therapy had markedly more calcium in their coronary arteries and aortic valves than did patients who had not been on such treatment.75


In addition to its effects on the coagulation cascade, vitamin K is now known to be involved in many of the body’s most critical functions. Bone mineralization and vascular calcification, two bodily functions affected by aging, are fundamentally related to each other through the actions of vitamin K. It is becoming increasingly clear that vitamin K antagonists (like warfarin) may have the unintended effects of exacerbating osteoporosis and atherosclerosis. Fortunately, the very science that revealed this new threat probably holds the answer to preventing it.

In 2005, a Japanese study demonstrated that the Gla-proteins governing coagulation require higher doses of warfarin for inhibition than do those that control bone mineralization.76 If confirmed, this exciting finding raises the possibility that careful, low-dose vitamin K supplementation could prevent warfarin’s deleterious effects on bone and blood vessel calcification, while preserving its beneficial effect of anticoagulation. University of Texas researchers have already demonstrated the safety and benefit of low-dose vitamin K supplementation in patients taking warfarin.68


In the last two years, scientists have uncovered several potential applications for vitamin K. Here is a summary of the most recent research demonstrating vitamin K’s wide applicability in human health beyond its well-known role in blood clotting.

  • Cancer-fighting effects. The hepatitis C virus is a leading cause of liver cancer. An 85-year-old man with hepatitis C and advanced liver cancer recently underwent marked regression of his tumor while using vitamin K therapy.78 Laboratory evidence in the last year provides an understanding of the mechanism of this anti-cancer effect.79-82 In 2005, vitamin K was also shown to have anti-leukemia effects.83 These anti-cancer capabilities seem to arise from vitamin K’s power to selectively inhibit cell growth and induce apoptosis (programmed cell death).84 This is an exciting and growing area of cancer therapy.
  • Improving cancer detection. Blood levels of “proteins induced by vitamin K absence or antagonist” (PIVKA) are elevated in liver cancer patients.85 PIVKA is a measure of insufficient vitamin K activity. In 2005, elevated PIVKA levels were correlated with a variety of other cancers.86,87 PIVKA testing may one day serve as a useful and sensitive marker of tumor progression or treatment success. Elevated PIVKA levels also raise the intriguing possibility that vitamin K deficiency could be related to the cause and possibly the treatment of some cancers.
  • Modulating inflammation. The vitamin K-dependent protein C has powerful anti-inflammatory capabilities. Activated protein C has been used in reducing the damage caused by the immune system in advanced bacterial sepsis.24,88
  • Supporting healthy bones. Earlier this year, researchers demonstrated that long-term use of anticoagulants is associated with increased risk of osteoporotic fractures.89 This is an unsurprising finding in light of other work demonstrating a link between anticoagulant drugs and abnormalities in measures of bone calcification.71 In a 2005 study, vitamin K-rich compounds in sweet potato leaves not only stimulated bone formation through vitamin K activity, but also seemed to inhibit bone resorption through the actions of other components.90
  • Protecting vascular health. Very recent work has shown that vitamin K antagonists such as warfarin may promote blood vessel calcification.45,91 Postmenopausal women who supplemented with vitamins D and K had less calcification and superior arterial vessel wall elasticity than placebo-treated subjects.92

Patients taking warfarin (Coumadin®) or other vitamin K antagonists should talk with their doctors about this recent literature, to learn whether regular, low-dose supplements of vitamin K (100 mcg/day), taken under careful medical supervision, may be right for them. Because of the considerable evidence for increasing the daily recommended dose of vitamin K,14,15,17,20 people who are not taking anticoagulant medication may want to consider beginning daily supplements of vitamin K to support the Gla-proteins that can slow osteoporosis and reduce arterial calcification.36 For people in good health, doses of 10 mg to 40 mg have been used.39


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