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No Effect of Red Clover–Derived Isoflavone Intervention on the Insulin-Like Growth Factor System in Women at Increased Risk of Colorectal Cancer

¹ Division of Experimental Therapy, Departments of ² Epidemiology, ³ Clinical Chemistry, ⁴ Gastroenterology and Hepatology, and ⁵ Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; ⁶ Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands; ⁷ Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Utrecht, the Netherlands; and ⁸ Department of Gastroenterology, Gelderse Vallei Hospital, Ede, the Netherlands

Requests for reprints: Matti A. Rookus, Department of Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Phone: 31-20512-2491; Fax: 31-20512-2322. E-mail: m.rookus{at}nki.nl

Background: Increased insulin-like growth factor (IGF)-I and IGF-II concentrations are related to increased colorectal cancer risk. Isoflavones have been associated with reduced colorectal cancer risk, and may affect the IGF system because of their weak estrogenic activity. The aim of the study was to investigate the effect of isolated isoflavones on serum concentrations of IGF system components.

Materials and Methods: We conducted a randomized, placebo-controlled, double-blinded, crossover trial in four hospitals in the Netherlands to investigate the effect of an 8-week supplementation with red clover–derived isoflavones (84 mg/d) on serum IGF-I concentrations. In addition, serum concentrations of IGF-II and IGF binding proteins (IGFBP)-1, IGFBP-2, and IGFBP-3 were assessed. Normal colorectal tissue biopsies were obtained after the first intervention period and mRNA expression of IGF-I, IGF-II, IGFBP-3, and IGF-IR was evaluated. Our study population consisted of 34 postmenopausal women with a family history of colorectal cancer or a personal history of colorectal adenomas.

Results: Isoflavone supplementation did not significantly affect serum concentrations of total IGF-I (mean relative within-person difference; IGF-I, –2.0%; 95% confidence interval, –8.0% to 3.9%). IGF-II and IGFBPs were also not significantly altered after isoflavone supplementation. Colorectal tissue mRNA expression of IGF system components did not significantly differ between individuals on isoflavone supplementation and those who received placebo.

Conclusions: The results of our trial, supported by a qualitative review of soy trials published to date, suggest that isoflavones do not significantly affect circulating levels of IGF system components. Increased levels of IGF-I, as observed in most of these trials, are likely due to simultaneous protein supplementation. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2585–93)