Prostate cancer: another aspect of the insulin-resistance syndrome?

Insulin resistance and compensatory hyperinsulinaemia are thought to be the underlying factors in the metabolic or insulin-resistance syndrome and can be controlled by diet and exercise. Hyperinsulinaemia has been shown to have a direct effect on the live, suppressing the production of sex hormone-binding globulin (SHBG) and insulin-like growth factor-binding proteins 1 and 2 (IGFBP-1, -2) while stimulating the production of insulin-like growth factor 1 (IGF-1). These factors have been proposed to be important modulators of hormone-related cancers, such as prostate cancer. Men adopting a low-fat diet and daily exercise reduced their levels of serum insulin and IGF-1, while increasing their levels of IGFBP-1 and sex hormone-binding globulin (SHBG). Cell-culture studies with LNCaP prostate cancer cells showed apoptosis of tumour cells and a reduction in serum-stimulated cell growth in the post diet and exercise serum. These results suggest that prostate cancer may be another aspect of the insulin-resistance syndrome and that adopting a low-fat diet combined with regular exercise may reduce the risk for prostate and other hormone-related cancers. This needs to be tested with prospective studies.

Changes in sex hormone-binding globulin, insulin, and serum lipids in postmenopausal women on a low-fat, high-fiber diet combined with exercise.

Dietary factors including fat and fiber have been reported to play a role in the development of breast cancer, possibly mediated by changes in estradiol. Diet and exercise have been shown to affect levels of sex hormone-binding globulin (SHBG), which in turn regulate the bioavailability of estradiol. Diet and exercise also affect insulin levels, which play a role in the synthesis of SHBG, and the hormone itself is a potent mitogen for many cancer cell lines. This study was designed to measure the effects of a low-fat, high-fiber diet, combined with regular aerobic exercise, on the levels of SHBG, insulin, and serum lipids in postmenopausal women with or without hormone replacement therapy (HRT). Two groups of postmenopausal women, 11 on HRT and 11 not on HRT, underwent a low-fat (1O% fat calories), high-fiber (65-70 g/day) diet-and-exercise intervention for three weeks. Serum SHBG, insulin, and lipids were measured before and after the regimen. After the intervention, SHBG levels were significantly increased for the women on HRT (44.5 +/- 3.4 vs. 62 +/- 6.4 nmol/l) and the women not on HRT (32.1 +/- 4.6 vs. 45.5 +/- 6.1 nmol/l, both changes p < 0.01). Also after the intervention, insulin levels were significantly reduced for the women on HRT (196 +/- 44.4 vs. 119.8 +/- 28.7 pmol/l) and the women not on HRT (144.2 +/- 17.9 vs. 115.5 +/- 20.8 pmol/l, both changes p < 0.01). Body mass index and total cholesterol were significantly reduced for both groups of women (all changes p < 0.01). Although the exact mechanism for the change in SHBG is not known, the increases in SHBG and reductions in insulin as a result of this lifestyle intervention should reduce the risk for breast cancer in postmenopausal women.

Effects of diet and exercise on insulin, sex hormone-binding globulin, and prostate-specific antigen.

A diet high in fat has been linked to prostate cancer, possibly through an influence on hormones. Sex hormone-binding globulin (SHBG) binds androgens and is regulated in part by insulin. Diet and exercise can modify insulin levels, potentially affecting SHBG and the biologically available levels of androgens. To determine the effects of a low-fat (< 10% of calories), high-fiber diet plus daily exercise on insulin, SHBG, prostate-specific antigen (PSA), and serum lipids, we measured the levels of these factors in the serum of 27 obese men undergoing a three-week diet-and-exercise program. Insulin decreased from 222 +/- 30 to 126 +/- 21 pmol/l (p < 0.01), and SHBG increased from 18 +/- 2 to 25 +/- 3 nmol/l (p < 0.01). Body mass index decreased from 35 +/- 1.9 to 33.4 +/- 1.8 kg/m2 (p < 0.01). PSA levels were normal and did not change significantly, although in a small subset of men (n = 3) with slightly elevated PSA levels (> 2.5 ng/ml) all showed a decrease. The three-week diet-and-exercise intervention decreased insulin and lipid levels while increasing SHBG. The increase in SHBG would result in more testosterone being bound and, therefore, less of the androgen available to act on the prostate. The decrease in insulin might also decrease mitogenic activity in the prostate. The diet-and-exercise regimen did not have a significant impact on normal PSA levels. Although modest, these changes may be protective against the development of prostate cancer.

Evidence of an inhibitory effect of diet and exercise on prostate cancer cell growth.

PURPOSE: A high fat diet and sedentary lifestyle may predispose men to prostate cancer through effects on serum factors such as hormones. We evaluated the effects of a low fat, high fiber diet and exercise intervention on serum stimulated growth of established prostate cancer cell lines. MATERIALS AND METHODS: Fasting serum was obtained from 13 overweight men before and after undergoing an 11-day low fat, high fiber diet and exercise intervention. Serum was also obtained from 8 men who had complied with the regimen for a mean of 14.2 years. Hormone dependent LNCaP and independent PC-3 prostate cancer cell lines were grown in culture medium containing 10% of subject pre-intervention or post-intervention serum and viable cells were counted after 48 hours. Anthropometry, serum free testosterone, lipids and glucose were measured in all subjects. RESULTS: Post-intervention serum from each of the 11-day intervention subjects reduced LNCaP cell growth by a mean of 30% compared with pre-intervention serum from each (p <0.01). LNCaP cell growth in serum from long-term subjects was 15% below that of post-intervention serum (p <0.01). There was no difference in the growth of PC-3 cells when cultured with serum from either intervention group. Serum free testosterone, body weight, glucose and lipids were significantly reduced in 11-day subjects. CONCLUSIONS: A low fat, high fiber diet and exercise intervention resulted in serum changes that significantly reduced the growth of androgen responsive LNCaP prostate cancer cells in vitro.

Decreased growth of human prostate LNCaP tumors in SCID mice fed a low-fat, soy protein diet with isoflavones.

Epidemiological studies suggest that high intake of dietary fat is a risk factor for the development of clinical prostate cancer. Soy protein has also been proposed to play a role in the prevention of prostate cancer, and one of the isoflavones in soy protein, genistein, inhibits the growth of human prostate cancer cell lines in vitro. This study was designed to evaluate whether altering dietary fat, soy protein, and isoflavone content affects the growth rate of a human androgen-sensitive prostate cancer cell line (LNCaP) grown in severe-combined immunodeficient (SCID) mice. SCID mice were randomized into four dietary groups: high-fat (42.0 kcal%) + casein, high-fat (42.0 kcal%) + soy protein + isoflavone extract, low-fat (12.0 kcal%) + casein, and low-fat (12.0 kcal%) + soy protein + isoflavone extract. After two weeks on these diets, the mice were injected subcutaneously with 1 x 10(5) LNCaP tumor cells and placed in separate cages (1 mouse/cage) to strictly control caloric intake. Isocaloric diets were given 3 days/wk, and tumor sizes were measured once per week. The tumor growth rates were slightly reduced in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In addition, the final tumor weights were reduced by 15% in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In this xenograft model for prostate cancer, there were statistically significant effects on tumor growth rate and final tumor weight attributable to a low-fat + soy protein + isoflavone extract diet.