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Soybean Isoflavones Improve Cardiovascular Risk Factors without Affecting the Reproductive System of Peripubertal Rhesus Monkeys^1,2,

Mary S. Anthony^*,3, Thomas B. Clarkson^*, Claude L. Hughes, Jr.^*,, Timothy M. Morgan^** and Gregory L. Burke^**

^* Comparative Medicine Clinical Research Center Department of Obstetrics and Gynecology, and ^** Department of Public Health Sciences, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157

Although the beneficial effects of dietary soybean protein compared with animal proteins on plasma lipids, lipoproteins and atheroscierosis have been known for about 50 years, it has been uncertain whether these effects are due to its amino acid concentrations or other components in soybeans. To assess the effect of soybean protein's alcohol-extractable components (including the isoflavonic phytoestrogens genistein and daidzein) on plasma lipid and lipoprotein concentrations and to establish its lack of effect on the reproductive system, we fed 27 peripubertal male and female rhesus monkeys moderately atherogenic diets in which the source of dietary protein was a soy isolate (20% by weight), either containing phytoestrogens (also termed isoflavones) or with the phytoestrogens removed by alcohol extraction. The study was a crossover design with each period lasting for 6 mo. The phytoestrogen-intact soy protein (compared with the alcohol-extracted soy protein) had favorable effects on plasma lipid and lipoprotein concentrations, specifically by significantly reducing LDL + VLDL cholesterol concentrations in both males and females (30–40% lower), significantly increasing high density lipoprotein cholesterol (HDLC) concentrations for females (15% higher) and significantly lowering total plasma cholesterol (TPC):HDLC ratios (20% lower for males and 50% lower for females). The phytoestrogens had no adverse effects on the reproductive systems of either the males or females, as evaluated by reproductive hormone concentrations and organ weights at necropsy. Thus, the isoflavones in soy protein improve cardiovascular disease risk factors without apparent deleterious effects on the reproductive system of peripubertal rhesus monkeys.

KEY WORDS: • rhesus monkeys • soybean protein • cardiovascular disease • reproductive organs • isoflavones • phytoestrogens

¹ Presented at the First International Symposium on the Role of Soy in Preventing and Treating Chronic Disease, February 20–23, 1994, Mesa, AZ (Anthony, M. S., Clarkson, T. B., Weddle, D. L., Wolfe, M. S. (1995) Effects of soy protein phytoestrogens on cardiovascular risk factors in rhesus monkeys. J. Nutr. 125: 803–804) and at the 67th Scientific Sessions of the American Heart Association, November 14–17, 1994, Dallas, TX (Antony, M. S., Clarkson, T. B., Hughes, C. L., Jr. (1994) Plant and mammalian estrogen effects on plasma lipids of female monkeys. Circulation 90: I-235).

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 4 April 1995. Revision accepted 16 August 1995.