Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective double-blinded clinical trial

Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):341-7. doi: 10.1161/ATVBAHA.107.153965. Epub 2007 Nov 21.


Objective: Clinical trials of vitamin E have failed to demonstrate a decrease in cardiovascular events. However, these studies did not address possible benefit to subgroups with increased oxidative stress. Haptoglobin (Hp), a major antioxidant protein, is a determinant of cardiovascular events in patients with Type 2 diabetes mellitus (DM). The Hp gene is polymorphic with 2 common alleles, 1 and 2. The Hp 2 allelic protein product provides inferior antioxidant protection compared with the Hp 1 allelic product. We sought to test the hypothesis that vitamin E could reduce cardiovascular events in DM individuals with the Hp 2-2 genotype, a subgroup that comprises 2% to 3% of the general population.

Methods and results: 1434 DM individuals > or = 55 years of age with the Hp 2-2 genotype were randomized to vitamin E (400 U/d) or placebo. The primary composite outcome was myocardial infarction, stroke, and cardiovascular death. At the first evaluation of events, 18 months after initiating the study, the primary outcome was significantly reduced in individuals receiving vitamin E (2.2%) compared with placebo (4.7%; P=0.01) and led to early termination of the study.

Conclusions: Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2-2 genotype ( NCT00220831).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antioxidants / therapeutic use*
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / genetics
  • Double-Blind Method
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Haptoglobins / genetics*
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / prevention & control*
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Pharmacogenetics
  • Prospective Studies
  • Stroke / prevention & control*
  • Tocopherols / therapeutic use*


  • Antioxidants
  • Haptoglobins
  • Tocopherols

Associated data