The paradox of antioxidants and cancer

Laxdale Ltd Kings Park House Laurelhill Business Park Stirling FK7 9JQ United Kingdom E-mail: agreen{at}laxdale.co.uk

Dear Sir:

In reference to van der Vliets's recent editorial in the Journal (1), there is one relatively simple hypothesis that helps to explain the evidence that antioxidants may both prevent and promote the growth of cancer. On the one hand, evidence that free radicals may be involved in the generation of mutations that help to initiate cancer is well known and widely reported. Less well known, but also well documented, is evidence that free radical mechanisms are involved in the elimination of cancer cells. Agents that generate free radicals have repeatedly been shown to kill cancer cells selectively while sparing normal cells (2–4). Antioxidants block this cancer-killing effect and accelerate cancer growth both in vitro and in vivo (2–5).

Because cancer has a preclinical incubation time of many years, there will always be a substantial number of persons with existing but undetected cancers in any large population that appears clinically healthy. A population of smokers is expected to include more cases of subclinical cancer than is a population of nonsmokers. When such a population is treated with antioxidants or placebos, the antioxidants may prevent cancer in those with no subclinical cancer but may accelerate the growth of hitherto undetected cancers. The latter effect will appear much more rapidly than will the former. Therefore, clinical trials of antioxidants of a realistic duration are more likely to increase than to decrease the number of clinically detectable cancers; trials of a very long duration may have the opposite effect.

REFERENCES

1. van der Vliet A. Cigarettes, cancer, and carotenoids: a continuing, unresolved antioxidant paradox. Am J Clin Nutr 2000;72:1421–3.
2. Begin ME, Ells G, Horrobin DF. Polyunsaturated fatty acid induced cytotoxicity against tumor cells and its relationship to lipid peroxidation. J Natl Cancer Inst 1988;80:188–94.
3. Begin ME. Effects of polyunsaturated fatty acids and of their oxidation products on cell survival. Chem Phys Lipids 1987;45:269–313.
4. Das UN, Begin ME, Ells G, Huang YS, Horrobin DF. Polyunsaturated fatty acids augment free radical generation in tumor cells in vitro. Biochem Biophys Res Commun 1987;145:15–24.
5. Lhuillery C, Cognault S, Germain E, Jourdan ML, Bougnoux P. Suppression of the promoter effect of polyunsaturated fatty acids by the absence of dietary vitamin E in experimental mammary carcinoma. Cancer Lett 1997;114:233–4.