Abstract
Two of the dietary tenets of the free radical theory of cancer, put forth by Denham Harman in 1962, require, in deference to newly accrued knowledge, refinement. The first was a recommendation for dietary reduction of vulnerable free radical targets, for example, polyunsaturated lipids. The second was the addition of one or more antioxidants to the diet. With respect to the first, it is now known that the equivalent levels of dietary ω-6, -3 polyunsaturated fatty acids (PUFA) have opposite effects upon photocarcinogenesis. Increasing levels of ω-6 PUFA exacerbate photocarcinogenesis, with regard to decreased tumor latent period and tumor multiplicity. Dietary ω-3 PUFA inhibits photocarcinogenesis, increasing tumor latent period and reducing tumor multiplicity. Yet the degree of unsaturation in both types of fats is almost equal. It is almost certain that the action of these two types of PUFA rests with the intermediates that each generates through the lipoxygenase and cyclooxygenase pathways. The general recommendation to reduce dietary PUFA as a means to free radical reduction and reduced cancer risk is oversimplified and points to the complexity faced when accurately refining this recommendation. The second recommendation requiring refinement, that is, reducing cancer risk by addition of one or more antioxidants to the diet, also represents a formidable task. Supplementation of an antioxidant into the complex milieu of the cell with its own intricate and complex defense system may result in untoward effects. In addition, each antioxidant exerts its own specific mechanism(s) of radical scavenging and may exert its own specific physiological responses. As an example, butylated hydroxytoluene’s mode of action in inhibiting photocarcinogenesis involves the chemical differentiation of nonliving stratum corneum that results in UVR-dose diminution to the target. Moreover, b-carotene supplementation in clinical trials had no effect on UVR-induced skin cancer and may, depending on carotenoid dose, animal age, and dietary regimen, actually exacerbate photocarcinogenesis. β-carotene supplementation did, however, increase the incidence of lung cancer in smokers. Both butylated hydroxytoluene’s and β-carotene potentiate hepatic Phase I and/or II detoxification systems that may further predispose the host to chemically induced carcinogenesis. Thus, it may be necessary to develop an algorithm for each antioxidant supplement based upon the benefit to be derived for nonmelanoma skin cancer and the potential risks to each individual for other forms of cancer. Until then, the best advice, with respect to antioxidant supplementation and cancer risk, is to consume a diet that contains a wide range of natural antioxidants.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.