chemoprevention of cancer
Epidemiologic studies have provided evidence that populations who consume large quantities of fruits and vegetables in their diets have a lower risk of cancer. It is hypothesized that carotenoids that are converted to vitamin A in the liver and intestine may be important in the primary chemoprevention of cancer.
The following mechanisms are proposed for the anticarcinogenic effects of carotenoids and retinoids:
Retinoic acid promotes differentiation of mucus-secreting epithelial tissues. Supplementation of the diet with beta-carotene and retinol is hypothesized to reverse squamous metaplasia and preneoplastic lesions in the respiratory tract of cigarette smokers and workers exposed to asbestos.
Fruits and vegetables provide antioxidants such as beta-carotene, vitamins C and E, and selenium that prevent oxidative damage to DNA.
Vitamin A can enhance immune responses; other retinoids may modulate inflammatory reactions that are potential sources of reactive oxygen and nitrogen intermediates.
Notwithstanding such theoretical considerations, clinical studies on the role of vitamin A supplementation and cancer risk have failed to provide clear answers.
Clinical trials using beta-carotene and retinyl palmitate as primary preventive agents against lung cancer were terminated because the participants showed an excess of lung cancers and increased mortality. On the other hand, 13-cis-retinoic acid was effective in prevention of secondary squamous cell carcinomas of the head and neck region.
These apparently conflicting results are not easily explained; however, there are multiple chemical forms of retinoids that alter gene expression, cell proliferation, differentiation, and apoptosis by binding to six different nuclear receptors. Some retinoids are associated with significant toxicity, including dry skin, conjunctivitis, and hypertriglyceridemia.
Until the biochemical and molecular mechanisms of action of individual retinoids and other antioxidants are understood, it is unwise to recommend dietary supplements for the primary chemoprevention of cancer.
However, a diet rich in fruits, vegetables, and unprocessed grains that is low in fat and animal protein has been associated with a decreased risk of cardiovascular disease and some types of cancer.
High animal fat intake combined with low fiber intake has been implicated in the causation of colon cancer.
The most convincing explanation for these associations is as follows: high fat intake increases the level of bile acids in the gut, which in turn modifies intestinal flora, favoring the growth of microaerophilic bacteria. The bile acids or bile acid metabolites produced by these bacteria might serve as carcinogens or promoters.
The protective effect of a high-fiber diet might relate to (1) increased stool bulk and decreased transit time, which decrease the exposure of mucosa to putative offenders, and (2) the capacity of certain fibers to bind carcinogens and thereby protect the mucosa.
Attempts to document these theories in clinical and experimental studies have, on the whole, led to contradictory results.
References
Hong WK, Sporn MB: Recent advances in chemoprevention of cancer. Science 278:1073, 1997.