Title: Do Antioxidants Interact?

Key words: Vitamins C (ascorbic acid), Vitamin E (alpha-tocopherol)

Date: Oct 2000

Category: Materia Medica

Type: Article


Do Antioxidants Interact?

Taking supplements of individual or multiple antioxidant vitamins is increasingly common in developed countries. The effects of this type of supplementation are also being studied in large scale randomised clinical trials in areas such as cancer prevention.

One area of interest in these studies is how the various antioxidant supplements might interact, particularly vitamin C and vitamin E.

For example, even though vitamin C is water-soluble, it seems to have an effect on lipid peroxidation and lipid membranes which may involve the fat-soluble vitamin E.

There is also some evidence that vitamin C supplements help to increase vitamin E levels by taking on part of the antioxidant workload. Vitamin C may be the "terminal small-molecule antioxidant in biological systems" (Free Radic Biol Med 1993: 14:649-53). Interactions between antioxidant vitamins may also be important when assessing the possible side-effects of long term supplementation.

To assess the level of interaction between these antioxidant vitamins, a double-blind crossover study has recently been completed. Thirty subjects were given placebo for 2 weeks followed by either vitamin C (500mg/day) or vitamin E (73·5 mg RRR-alpha-tocopherol acetate/day) or placebo for a further 6 weeks. After a 2 month washout period, these supplements were swapped over. Fasting blood was collected for vitamin assay.

This study was carefully designed, with a lengthy washout period between the double-blinded treatment phases. It also used the appropriate measure of vitamin E status, i.e. corrected for lipid concentrations.

Supplementing the normal dietary intake with either of these vitamin supplements produced a significant increase in plasma antioxidant activity and glutathione peroxidase levels. It also caused a a decrease in urate, total cholesterol and triacylglycerol levels (p<0·05).

These results indicate a significant interaction between the levels of these vitamins when each is taken individually. However, the study did not investigate the reasons for this observation.

With Vitamin C supplementation

Baseline level

After supplementation

Statistical significance

Ascorbic acid*








With Vitamin E


Ascorbic acid*









* Plasma ascorbic acid (µmol/l)

** Lipid-standardised plasma alpha tocopherol (µmol/mmol)

Reference: Br. J Nutrition 2000;84: 261-267