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BOSTON, MASSACHUSETTS. No clinical trials or epidemiologic studies have ever reported an association
between vitamin E supplementation and increased risk of bleeding or hemorrhagic stroke – not even in
patients taking warfarin. As a matter of fact, a clinical study found no change in coagulant activity in patients
with coronary artery disease who were taking warfarin and 100-400 IU/day of vitamin E. It is, however,
possible that patients with low vitamin K status could experience a decrease in coagulation time if warfarin
therapy is combined with large doses (800-1200 IU/day) of vitamin E.
A team of American, German and Japanese researchers has just completed a study aimed at determining if vitamin E supplementation on its own affects vitamin K status or coagulation time in patients not treated with warfarin. Their study involved 38 men and women with rheumatoid arthritis and 32 healthy men participating in two independent 12-week randomized clinical trials of vitamin E supplementation. All trial participants were given 1000 IU/day of natural vitamin E. The researchers used plasma concentration of proteins induced by vitamin K absence-factor II, or PIVKA-II for short, as a sensitive measure of vitamin K status. A normal value for PIVKA-II is 2.4 ng/mL or less and values higher than this indicate poorer vitamin K status. At the end of the 12-week supplementation period PIVKA-II had increased from 1.7 to 16.1 ng/mL in the rheumatoid arthritis group and from 1.8 to 5.3 ng/mL in the healthy men. Thus, it would appear that supplementation with a high dose of vitamin E does indeed reduce body stores of vitamin K. The vitamin E supplementation had no effect on prothrombin time (INR) and its effect on PIVKA-II was insignificant when compared with the effect of warfarin – a powerful vitamin K destroyer. PIVKA-II concentrations in patients on warfarin are around 750 ng/mL or 140 times higher than that experienced in healthy men taking 1000 IU/day of vitamin E.
The researchers conclude that high-dose vitamin E supplementation does reduce vitamin K status, but are
uncertain whether this interaction is immaterial, beneficial (reduced stroke risk) or harmful (loss of bone
density). Editor's comment: This study highlights the possibility of interaction between supplements and adds to the growing body of evidence to the fact that high-dose supplementation with a single vitamin may not be desirable. A balanced approach is better. Nevertheless, daily supplementation with 400 IU/day of vitamin E has been found safe in numerous studies and is highly unlikely to affect prothrombin time or bleeding tendency in patients taking warfarin.
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