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.

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.

Prostate cancer risk is associated with a high-fat diet and a sedentary lifestyle. Placing men on a low-fat diet-and-exercise intervention reduces serum hormones, including estradiol, insulin, and free testosterone, that may play a role in prostate cancer growth. Eight men participated in a low-fat diet-and-exercise program for a mean of 14.2 yr, and LNCaP cell growth in culture was measured in medium supplemented with 10% of each subject's serum as well as with testosterone, estradiol, and insulin added singly or in combination. These results were compared in the fetal bovine serum (FBS)-stimulated growth and cell growth in serum obtained from a control group of 14 overweight men. In separate tissue culture experiments, LNCaP and PC-3 cell growth was also measured in response to the addition of testosterone, estradiol, or insulin to steroid-stripped FBS. LNCaP cell growth in medium with subject serum was 40% less than in FBS-stimulated medium and 49% less than in medium with serum from control, overweight men. Addition of testosterone, estradiol, and insulin to serum from diet-and-exercise subjects significantly stimulated LNCaP cell growth in vitro but accounted for only about half of the difference between the control and diet-and-exercise subjects. Thus other serum changes must also account for the significant reduction in LNCaP cell growth observed using medium with serum from the diet-and-exercise subjects in the cell culture assay.

A low-fat diet and exercise intervention induces in-vivo changes in the circulating IGF axis and is associated with reduced growth and enhanced apoptosis/necrosis of LNCaP tumor cells in vitro.

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.