Dietary Glycemic Index May Influence Cancer Risk by Modulating IGF-I Activity: A Hypothesis

Abstract

A high-glycemic-index diet increases hepatocyte exposure to insulin, and thus should up-regulate IGF-I activity—both by stimulating IGF-I synthesis and by suppressing hepatic production of IGFBP-1. The resulting increase in IGF-I activity might be expected to have a significant cancer promotional impact in light of IGF-I's role as a progressional growth factor and anti-apoptotic agent in a great many normal and neoplastic tissues. Although direct epidemiological data linking the glycemic index of habitual diets to cancer risk are currently scarce, the profusion of reports suggesting that legumes—one of the lowest-glycemic-index staple foods—are cancer preventive is consistent with the thesis that a low-glycemic-index diet is protective in this regard; the apparent protection associated with high intakes of fruit and of fiber-rich foods may also be partially traceable to reduced glycemia. Slowly digested starch may be stored preferentially in the liver, accounting for its favorable impact on satiety and glycemic regulation; through induction of hepatic glucokinase, high-dose biotin may enhance hepatic uptake of portal glucose and thus reduce the effective glycemic index of meals. Choosing low-glycemic index starchy foods is only one of a number of measures—which include exercise training, a very-low-fat vegan diet, appropriate weight reduction, caloric restriction, and intake of chromium, biguanides, and possibly high-dose biotin—that tend to minimize diurnal insulin secretion in the context of good glycemic control, thereby decreasing risk for atherothrombotic disease, diabetes, obesity, and cancer, and perhaps even slowing the aging process.