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1 From the University of California, Los Angeles, Center for Human Nutrition.
See corresponding article on page 689.
Both benign prostatic hyperplasia (BPH) and prostate cancer become more common as men age, and both disorders are likely to result from a gene-environment interaction (1, 2). The cause of BPH is not well understood, but sex hormones, fatty acids, and interactive effects of estradiol and testosterone have been proposed as playing important roles in the pathogenesis of this common disorder. For centuries it has been known that BPH occurs mainly in older men and that it does not develop in men whose testes are removed before puberty. For this reason, some researchers believe that factors related to aging and the testes may spur the development of BPH.
Throughout their lives, men produce both testosterone, an essential male hormone, and small amounts of estrogen, a female hormone. As men age, the amount of active testosterone in the blood decreases, leaving a higher proportion of estrogen. The results of studies in animals suggest that BPH may occur because the higher amount of estrogen within the gland increases the activity of substances that promote cell growth. Diet and lifestyle may influence BPH in part via effects on reproductive hormones in susceptible men (3).
Evidence of an increased risk of prostate cancer and BPH in association with Western dietary patterns can be found in both epidemiologic and animal studies. Men moving from countries with a low risk of these diseases, such as Japan, to countries with a high risk of these diseases, such as the United States, increase their risk of prostate cancer in one generation. Although similar data are not available for BPH, the report by Suzuki et al (4) in this issue of the Journal provides evidence that increased intakes of energy, protein, and certain polyunsaturated fats in the diet may be associated with modest increases in the risk of BPH. There is recent evidence that increased proliferation and associated inflammation may lead to preneoplastic lesions in the prostate gland. For example, areas of proliferative inflammatory atrophy were found adjacent to preneoplastic foci of prostatic intraepithelial neoplasia in the prostates of older men (5). Although BPH is clearly not cancer, factors in the diet that increase prostate cell proliferation may also play a role in increasing the risk of prostate cancer.
Western-style dietary patterns increase epithelial cell proliferation in the prostate gland of mice. In fact, a diet high in fat and low in calcium and vitamin D fed to C57BL/6J mice induced hyperproliferation in the anterior and dorsal lobes of the prostate gland in comparison with a standard AIN (American Institute of Nutrition)-76A diet (6). Although mice do not get BPH, the anterior and dorsal lobes of the mouse prostate are homologous with the human prostate in embryologic origin and histologic structure.
The canine prostate has often been proposed as a model for abnormal growth of the human gland in aging men because hyperplasia of the prostate has been estimated to be present in 100% of old intact dogs. The age-related expansion of proliferating prostate basal cell populations is thought to be mediated by sex steroids. For example, prostatic hyperplasia can be induced by administration of both 17ß-estradiol and 5-androstane-3, 17ß-diol, or dihydrotestosterone (7) to young castrated beagles, in which the gland had been allowed to involute for 1 mo. These data were used to imply that estrogens and androgens may play a role in prostatic enlargement. From a nutritional standpoint, this may be significant because 80% of circulating estrogens in men arise from aromatization of androgens in the peripheral fat tissue and because obese men have higher circulating estrogen concentrations than do lean men (8).
Increased proliferation of prostate cells due to polyunsaturated fats in the diet may also result from increased oxidative stress in the prostate gland. The Western diet is not only characterized by a high energy content (a high proportion of which comes from animal fats and polyunsaturated fats) but also by a low content of fruit, vegetables, and whole grains, which are known to counter oxidative stress (9). A high intake of tomato products and high blood concentrations of lycopene, the primary carotenoid antioxidant found in prostate tissue, were associated with a reduced risk of prostate cancer in the same cohort studied with regard to BPH (10). There was no mention of any inverse correlation with fruit and vegetable intake in the present report, but this is certainly a high priority area for future investigation. Comparisons of the effects on risk of BPH of diets low in polyunsaturated fat, animal protein, and total energy but high in antioxidants (ie, fruit and vegetables) with typical Western diets (which are high in fat and polyunsaturated fat but low in antioxidants) could help in developing effective population-wide strategies for preventing BPH.
Coal miners would often send a canary into a newly excavated tunnel. If the canary died, it meant that the tunnel was not safe. Perhaps hyperproliferation and enlargement of the prostate gland exposed to the inflammatory, proliferative, and prooxidative effects of the Western diet is a canary of sorts, telling us something about the potentially damaging effects of our dietary pattern. Perhaps it is time to consider dietary intervention studies as one way to define strategies to prevent the common problem of prostatic enlargement and BPH. These insights may lead to useful strategies for the prevention of prostate cancer—the most common form of cancer in men.
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