RESPONSE: Re: Plasma Insulin-Like Growth Factor-I, Insulin-Like Growth Factor-Binding Proteins, and Prostate Cancer Risk: a Prospective Study

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Drs. Allen and Key present evidence that suggests a relationship between serum IGF-I concentrations and diets rich in animal protein and associated essential amino acids. This very interesting observation is in line with results from several intervention studies in humans that showed that the intake level of protein, and especially of essential amino acids, is a key determinant of circulating IGF-I levels (1,2). We share the view of Drs. Allen and Key that an elevated intake of animal protein might, at least partly, explain the high incidence rates of prostate cancer in westernized, industrial countries.

A parallel hypothesis is that the balance between energy intake and expenditure also affects circulating IGF-I levels, which in turn affect prostate cancer risk. However, the relationship between plasma levels of IGF-I, prostate cancer, and adiposity (as a result of high energy intake and low expenditure) is complex. Results from a large number of epidemiologic studies [reviewed in (3)] have shown no consistent relationship between prostate cancer risk and body mass index (BMI). Furthermore, cross-sectional studies [reviewed in (4)], mostly in well-nourished Western populations, have also not shown a simple, direct relationship between BMI and circulating levels of IGF-I. On the contrary, a comparatively elevated BMI (>30 kg/m²) is associated with decreased, rather than increased, levels of IGF-I (4). Nevertheless, we would not rule out the existence of a positive association between IGF-I and adiposity in populations where the majority of subjects have a BMI below 22–24 kg/m², as is the case in many developing countries where prostate cancer risk is low. This would imply a nonlinear relationship between adiposity and IGF-I levels, with peak levels of IGF-I occurring in individuals with a BMI of about 25 kg/m², and a gradual decrease at higher levels of adiposity. This hypothesis—that increasing IGF-I levels accompany increasing adiposity in nonobese individuals—fits with observations made in patients with anorexia nervosa and also fits with observations that only a minimum level of endogenous insulin is required for tissues to respond optimally to growth hormone, the principal stimulus for IGF-I synthesis (5,6). In contrast, obesity and chronic hyperinsulinemia decrease pituitary growth hormone secretion and, hence, cause a drop in the level of IGF-I (3).