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Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status^1,2,3,4

¹ From the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston (SLB, JMS, RR, GED, and JBB); the Walther Straub Institute of Pharmacology and Toxicology, Ludwig Maximilians University of Munich, Munich, Germany (IG); and the Saga Nutraceuticals Research Institute, Saga, Japan (KH)

Background: Cases of enhanced anticoagulant effect in response to high-dose vitamin E supplementation have been reported among patients taking oral anticoagulants. Although a vitamin E–vitamin K interaction was proposed to underlie this effect, it has not been systematically investigated in adults with normal baseline coagulation status.

Objective: The objective was to study the effect of 12 wk of supplementation with 1000 IU RRR--tocopherol/d on biochemical measures of vitamin K status in men and women not taking oral anticoagulants.

Design: Vitamin K status, which was assessed with the use of plasma phylloquinone concentrations, the degree of under--carboxylation of prothrombin (proteins induced by vitamin K absence–factor II, PIVKA-II), and the percentage of undercarboxylated osteocalcin (ucOC), was determined in 38 men and women with rheumatoid arthritis (study A) and in 32 healthy men (study B) participating in 2 independent, 12-wk randomized clinical trials of vitamin E supplementation (1000 IU/d).

Results: Mean (± SD) PIVKA-II increased from 1.7 ± 1.7 to 11.9 ± 16.1 ng/mL (P < 0.001) in study A and from 1.8 ± 0.6 to 5.3 ± 3.9 ng/mL (P < 0.001) in study B in response to 12 wk of vitamin E supplementation. An increase in PIVKA-II is indicative of poor vitamin K status. In contrast, the other measures of vitamin K status (ie, plasma phylloquinone concentration and percentage of ucOC) did not change significantly in response to the supplementation.

Conclusions: High-dose vitamin E supplementation increased PIVKA-II in adults not receiving oral anticoagulant therapy. The clinical significance of these changes warrants further investigation, but high doses of vitamin E may antagonize vitamin K. Whether such an interaction is potentially beneficial or harmful remains to be determined.

Key Words: Vitamin K • vitamin E • proteins induced by vitamin K absence • PIVKA-II • coagulation

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