Life Extension 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
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
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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