A secondary analysis of the Women’s Health Study was conducted to evaluate
whether vitamin E supplementation reduced the risk of venous thromboembolism. 
According to a 2008 U.S. Surgeon General’s report, at least 100,000 deaths in the
United States result from deep vein thrombosis and pulmonary embolism induced by
venous thromboembolism.  Women 45 years and older (n=39,876) were randomized
to 600 IU vitamin E (α-tocopherol) or a placebo every other day.  Genotyping for
coagulation disorders (factor V Leiden, G20210A prothrombin, and 677C>T MTHFR
polymorphisms) was completed for 26,779 participants.  Documented cases of venous
thromboembolism, including unprovoked venous thromboembolism (occurrence in
absence of trauma, surgery, or malignancy) were the primary outcome measures.  There
were 482 cases (213 supplemented and 269 placebo) of venous thromboembolism. 
Vitamin E supplementation was associated with a 21 percent reduction of venous
thromboembolism, a 27 percent reduction of unprovoked venous thromboembolism, and
a 28 percent reduction of pulmonary embolism.  In participants with a history of venous
thromboembolism or with factor V Leiden or prothrombin mutation, supplementation
was associated with a 40-49 percent risk reduction.  Adverse coagulation effects, such
as hemorrhagic stroke or hematuria (the presence of red blood cells in the urine), did
not differ between groups.

Although additional confi rmation studies are needed, this
study supports the benefi ts of vitamin E supplementation in the prevention of venous
thromboembolism, especially in those with prior history or genetic predisposition.

Funding: National Heart, Lung, and Blood Institute and National Cancer Institute, NIH;
Natural Source Vitamin E Association; and Bayer Healthcare.
Goldhaber, RY Zee, and
JE Buring.  Circulation
(Circulation) 2007
116(13):1497-1503.