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Nutrition and Disease

Isolated Isoflavones Do Not Affect the Circulating Insulin-Like Growth Factor System in Men at Increased Colorectal Cancer Risk¹

² Division of Experimental Therapy, ³ Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; ⁴ Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands; ⁵ Department of Clinical Chemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands; ⁶ Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Utrecht, The Netherlands; ⁷ Fred Hutchinson Cancer Research Center, Seattle, Washington; ⁸ Department of Gastroenterology and Hepatology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; ⁹ Department of Gastroenterology, Gelderse Vallei Hospital, Ede, The Netherlands; and ¹⁰ Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

^* To whom correspondence should be addressed. E-mail: m.rookus{at}nki.nl.

Epidemiological studies show that increased insulin-like growth factor (IGF)-I concentrations are related to increased colorectal cancer risk. A reduced colorectal cancer risk has been associated with isoflavones, which might affect the IGF-system because of their weak estrogenic activity. We conducted a randomized, placebo-controlled, double-blind crossover study to investigate the effect of an 8-wk isolated isoflavone supplementation (84 mg/d) on serum concentrations of total IGF-I, free IGF-I, total IGF-II, IGF binding protein (BP)-1, IGFBP-2, and IGFBP-3. Additionally, we investigated whether IGF-system component differences were related to concentrations of the more potent estrogenic isoflavone metabolite, equol. Our study population consisted of 37 men with a family history of colorectal cancer or a personal history of colorectal adenomas. Isoflavone supplementation did not significantly affect serum total IGF-I concentrations (relative difference between serum total IGF-I concentrations after isoflavone supplementation and after placebo: –1.3%, 95% CI –8.6 to 6.0%). Neither free IGF-I, nor total IGF-II, IGFBP-1, IGFBP-2, or IGFBP-3 concentrations were significantly altered. Interestingly, the change in serum IGF-I concentrations after isoflavone supplementation was negatively associated with serum equol concentrations (r = –0.49, P = 0.002). In conclusion, isolated isoflavones did not affect the circulating IGF-system in a male high-risk population for colorectal cancer. However, to our knowledge, this is the first study that suggests isoflavones might have an IGF-I lowering effect in equol producers only. This underlines the importance of taking into account equol status in future isoflavone intervention studies.

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