Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study.
BACKGROUND
Supplementation with vitamin E may antagonize vitamin K in healthy adults, but it is unclear whether intake of vitamin E decreases the risk of venous thromboembolism (VTE).


RESULTS
The Women's Health Study randomized 39,876 women > or = 45 years of age to receive 600 IU of natural source vitamin E or placebo on alternate days. Before randomization, 26,779 participants gave blood samples, which were used to determine factor V Leiden, G20210A prothrombin, and 677C>T MTHFR polymorphisms. Documented VTE (including deep vein thrombosis or pulmonary embolism) and unprovoked VTE (no recent surgery, trauma, or cancer diagnosis) were prospectively evaluated, secondary end points of the trial. During a median follow-up period of 10.2 years, VTE occurred in 482 women: 213 in the vitamin E group and 269 in the placebo group, a significant 21% hazard reduction (relative hazard, 0.79; 95% CI, 0.66 to 0.94; P=0.010). For unprovoked VTE, the hazard reduction was 27% (relative hazard, 0.73; 95% CI, 0.57 to 0.94; P=0.016). In subgroup analyses, the 3% of participants who reported VTE before randomization had a 44% hazard reduction (relative hazard, 0.56; 95% CI, 0.31 to 1.00; P=0.048), whereas women without prior VTE had an 18% hazard reduction (relative hazard 0.82; 95% CI, 0.68 to 0.99; P=0.040). Women with either factor V Leiden or the prothrombin mutation had a 49% hazard reduction associated with vitamin E treatment (relative hazard, 0.51; 95% CI, 0.30 to 0.87; P=0.014).


CONCLUSIONS
These data suggest that supplementation with vitamin E may reduce the risk of VTE in women, and those with a prior history or genetic predisposition may particularly benefit.
Glynn
Robert J
RJ
Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave E, Boston, MA 02215-1204, USA. rglynn@rics.bwh.harvard.edu
Ridker
Paul M
PM
Goldhaber
Samuel Z
SZ
Zee
Robert Y L
RY
Buring
Julie E
JE
D020413:3' Untranslated Regions / Q000235:genetics; D020016:Activated Protein C Resistance / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005165:Factor V / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011516:Prothrombin / Q000235:genetics; D011655:Pulmonary Embolism / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D012008:Recurrence; D040242:Risk Reduction Behavior; D019851:Thrombophilia / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D014810:Vitamin E / Q000008:administration & dosage / Q000627:therapeutic use*
D020413:3' Untranslated Regions; D010975:Platelet Aggregation Inhibitors; C095381:factor V Leiden; D014810:Vitamin E; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D001241:Aspirin