Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a randomized controlled trial

Am J Clin Nutr. 2002 Sep;76(3):549-55. doi: 10.1093/ajcn/76.3.549.


Background: Lipid peroxidation may be important in the pathogenesis of atherosclerosis, particularly in its earliest stages. Evidence predominantly from in vitro studies suggests that antioxidant vitamins can prevent lipid peroxidation and that vitamin C and vitamin E have synergistic effects. However, in vivo evidence in support of these hypotheses is sparse.

Objective: The objective was to determine the effects of vitamin C and vitamin E, alone or in combination, on in vivo lipid peroxidation.

Design: We conducted a placebo-controlled, 2 x 2 factorial trial of vitamin C (500 mg ascorbate/d) and vitamin E (400 IU RRR-alpha-tocopheryl acetate/d) supplementation in 184 nonsmokers. The mean duration of supplementation was 2 mo. The outcome measures were changes from baseline in urinary 8-iso-prostaglandin F(2alpha), urinary malondialdehyde + 4-hydroxyalkenals, and serum oxygen-radical absorbance capacity.

Results: The within-group mean changes (and 95% CIs) in urinary 8-iso-prostaglandin F(2alpha) (pg/mg creatinine) were 9.0 (-125.1, 143.1), -150.0 (-275.4, -24.6), -141.3 (-230.5, -52.1), and -112.5 (-234.8, 9.8) in the placebo, vitamin C alone, vitamin E alone, and vitamins C + E groups, respectively. No synergistic effect of these 2 vitamins on urinary 8-iso-prostaglandin F(2alpha) was observed (P = 0.12). Neither vitamin had an effect on urinary malondialdehyde + 4-hydroxyalkenals. Vitamin C, but not vitamin E, increased serum oxygen-radical absorbance capacity (P = 0.01).

Conclusions: Supplementation with vitamin C or vitamin E alone reduced lipid peroxidation to a similar extent. Supplementation with a combination of vitamins C and E conferred no benefit beyond that of either vitamin alone.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antioxidants / administration & dosage*
  • Ascorbic Acid / administration & dosage*
  • Dinoprost* / analogs & derivatives*
  • F2-Isoprostanes / urine
  • Female
  • Humans
  • Lipid Peroxidation / drug effects*
  • Male
  • Malondialdehyde / urine
  • Middle Aged
  • Placebos
  • Reactive Oxygen Species / blood
  • Tocopherols
  • Treatment Outcome
  • alpha-Tocopherol / administration & dosage*
  • alpha-Tocopherol / analogs & derivatives*
  • alpha-Tocopherol / blood


  • Antioxidants
  • F2-Isoprostanes
  • Placebos
  • Reactive Oxygen Species
  • 8-epi-prostaglandin F2alpha
  • Malondialdehyde
  • Dinoprost
  • alpha-Tocopherol
  • Ascorbic Acid
  • Tocopherols