Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study

Circulation. 2007 Sep 25;116(13):1497-503. doi: 10.1161/CIRCULATIONAHA.107.716407. Epub 2007 Sep 10.

Abstract

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).

Methods and 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions / genetics
  • Activated Protein C Resistance / complications
  • Activated Protein C Resistance / epidemiology
  • Activated Protein C Resistance / genetics
  • Adult
  • Aspirin / administration & dosage
  • Aspirin / therapeutic use
  • Double-Blind Method
  • Drug Administration Schedule
  • Factor V / analysis
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Incidence
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prothrombin / genetics
  • Pulmonary Embolism / epidemiology
  • Pulmonary Embolism / etiology
  • Pulmonary Embolism / prevention & control*
  • Recurrence
  • Risk Reduction Behavior
  • Thrombophilia / complications
  • Thrombophilia / drug therapy
  • Thrombophilia / genetics
  • Treatment Outcome
  • Venous Thrombosis / epidemiology
  • Venous Thrombosis / etiology
  • Venous Thrombosis / prevention & control*
  • Vitamin E / administration & dosage
  • Vitamin E / therapeutic use*

Substances

  • 3' Untranslated Regions
  • Platelet Aggregation Inhibitors
  • factor V Leiden
  • Vitamin E
  • Factor V
  • Prothrombin
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Aspirin