Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial

Lancet. 2002 Mar 30;359(9312):1108-13. doi: 10.1016/S0140-6736(02)08154-0.


Background: Cardiac transplantation is associated with oxidant stress, which may contribute to the development of accelerated coronary arteriosclerosis. We postulated that treatment with antioxidant vitamins C and E would retard the progression of transplant-associated arteriosclerosis.

Methods: In a double-blind prospective study, 40 patients (0-2 years after cardiac transplantation) were randomly assigned vitamin C 500 mg plus vitamin E 400 IU, each twice daily (n=19), or placebo (n=21) for 1 year. The primary endpoint was the change in average intimal index (plaque area divided by vessel area) measured by intravascular ultrasonography (IVUS). Coronary endothelium-dependent vasoreactivity was assessed with intracoronary acetylcholine infusions. IVUS, coronary vasoreactivity, and vitamin C and E plasma concentrations were assessed at baseline and at 1 year follow-up. All patients received pravastatin. Analyses were by intention to treat.

Findings: Vitamin C and E concentrations increased in the vitamin group (vitamin C 43 [SD 21] to 103 [43] mmol/L; vitamin E 24 [14] to 65 [27] mmol/L) but did not change in the placebo group (vitamin C 45 [15] vs 43 [16] mmol/L; vitamin E 27 [14] vs 27 [9] mmol/L; p<0.0001 for difference between groups). During 1 year of treatment, the intimal index increased in the placebo group by 8% (SE 2) but did not change significantly in the treatment group (0.8% [1]; p=0.008). Coronary endothelial function remained stable in both groups.

Interpretation: Supplementation with antioxidant vitamins C and E retards the early progression of transplant-associated coronary arteriosclerosis.

Publication types

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

MeSH terms

  • Antioxidants / therapeutic use*
  • Ascorbic Acid / therapeutic use*
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / physiopathology
  • Coronary Artery Disease / prevention & control*
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / physiopathology
  • Disease Progression
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endothelium, Vascular / physiopathology
  • Female
  • Heart Transplantation / adverse effects*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Tunica Intima / diagnostic imaging
  • Ultrasonography, Interventional
  • Vasodilation / drug effects
  • Vitamin E / therapeutic use*


  • Antioxidants
  • Vitamin E
  • Ascorbic Acid