Long-term effect of combined vitamins E and C on coronary and peripheral endothelial function

J Am Coll Cardiol. 2004 Feb 18;43(4):629-34. doi: 10.1016/j.jacc.2003.08.051.


Objectives: We tested whether long-term administration of antioxidant vitamins C and E improves coronary and brachial artery endothelial function in patients with coronary artery disease (CAD).

Background: Endothelial function is a sensitive indicator of vascular health. Oxidant stress and oxidized low-density lipoprotein (LDL) impair endothelial function by reducing nitric oxide bioavailability in the artery wall.

Methods: We randomly assigned 30 subjects with CAD to combined vitamin E (800 IU per day) and C (1000 mg per day) or to placebos in a double-blind trial. Coronary artery endothelial function was measured as the change in coronary artery diameter to acetylcholine infusions (n = 18 patients), and brachial artery endothelial function was assessed by flow-mediated dilation (n = 25 patients) at baseline and six months. Plasma markers of oxidant stress (oxidized LDL and autoantibodies) were also measured.

Results: Plasma alpha-tocopherol (p < 0.001) and ascorbic acid (p < 0.02) increased with active therapy. Compared to placebo, there was no improvement in coronary and brachial endothelial vasomotor function over six months. Although vitamins C and E tended to reduce F2-isoprostanes (p = 0.065), they failed to alter oxidized LDL or autoantibodies to oxidized LDL.

Conclusions: Long-term oral vitamins C and E do not improve key mechanisms in the biology of atherosclerosis or endothelial dysfunction, or reduce LDL oxidation in vivo.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / therapeutic use*
  • Brachial Artery / drug effects
  • Coronary Disease / drug therapy*
  • Coronary Disease / physiopathology
  • Coronary Vessels / drug effects
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • Time Factors
  • Vasodilation / physiology
  • Vitamin E / administration & dosage
  • Vitamin E / therapeutic use*


  • Antioxidants
  • Vitamin E
  • Ascorbic Acid