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Isoflavone-rich soy protein prevents loss of hip lean mass but does not prevent the shift in regional fat distribution in perimenopausal women

Moeller, Laura E. MS1; Peterson, Charles T. MS3; Hanson, Kathy B. PhD2; Dent, Sarah B. MS, RD2; Lewis, Douglas S. PhD5; King, Douglas S. PhD4; Alekel, D. Lee PhD2


Objective: Menopause-induced estrogen deficiency increases the risk of cardiovascular disease, which is related to a shift in regional fat distribution. We tested the hypothesis that estrogen-like isoflavones in soy protein isolate (SPI+) would lessen both regional fat gain and lean loss compared with isoflavone-poor soy (SPI−).

Design: Perimenopausal participants (N = 69) were randomly assigned (double-blind) to 24 weeks of treatment (40 g soy or whey protein per day): SPI+ (n = 24), SPI− (n = 24), or whey control (n = 21); each participant had blood drawn in the fasted (12 hours) state, had physical activity assessed, and kept a 5-day food diary. Dual-energy x-ray absorptiometry was used to examine the effects of SPI+ on regional fat and lean tissue distribution changes in the waist, hip, and thigh regions.

Results: Mean body mass increased (P < 0.01) in each group, but treatment had no effect on gain in overall body mass, fat mass, or lean mass using analysis of variance. In all treatment groups combined, lean mass increased in each region; fat mass increased only in the waist region. Treatment had an effect (P = 0.039) on hip lean mass and a marginal effect (P = 0.077) on thigh fat. Regression analyses revealed that SPI+ diminished the increase in thigh fat (P = 0.018) and heightened the increase in hip lean (P = 0.035) mass. Carbohydrate intake (P = 0.006) and cohort (reflective of season; P = 0.011) contributed to the gain in thigh fat. Total protein intake (P = 0.0012), plasma insulin (P = 0.0034), and physical activity (P = 0.047) contributed to the gain in hip lean mass.

Conclusions: Gain in hip lean mass was greater (P = 0.014) in SPI+ than other groups, but SPI+ did not reduce the disease-promoting menopausal shift in regional fat mass.

Menopause is associated with several changes that contribute to increased risk of cardiovascular disease (CVD), including a gynoid-to-android shift in regional fat distribution (RFD). 1 Android fat is located in the torso, whereas gynoid fat is located in the gluteal and femoral regions. 2 In females, RFD is usually of the gynoid pattern during the reproductive years but shifts to the android pattern at menopause. 3–6 Menopause is also associated with a decrease in lean mass and subsequent decrease in resting metabolic rate. 2 The android fat pattern is strongly associated with CVD risk factors, including insulin insensitivity, 1 noninsulin-dependent diabetes mellitus, 7,8 hypertension, 9 dyslipidemia, 10 and myocardial infarction. 7 In contrast, the gynoid fat pattern is not associated with such CVD risk factors and clinical outcomes. 2

Estrogen replacement therapy and combined estrogen-progestogen hormone replacement therapy were once theorized to improve the CVD risk profile in women by attenuating the menopausal shift in RFD. 11,12 However, after the results of the Women's Health Initiative and because of contraindications, such as preexisting breast or endometrial neoplasia, 13 and undesirable side effects, conventional hormone therapy is not appropriate for every menopausal woman. Many women seek alternative menopausal therapies, and estrogen-like isoflavones (genistein, daidzein, and glycitein) 14 in soy may be one such alternative. Isoflavones act as selective estrogen receptor modulators, binding to estrogen receptors (ERα and ERβ) with differing affinities, thereby exerting tissue-specific estrogenic and antiestrogenic effects. 15 Little is known about the effects of isoflavones on overall body composition or fat and lean tissue distribution.

Although epidemiological evidence suggests a potential role for isoflavones in the prevention of CVD, 16 no prospective human studies have been published on the effects of isoflavone-rich soy protein (SPI+) on regional fat and lean tissue distribution in perimenopausal women. The purpose of this 24-week pilot study was to investigate the effects of SPI+ on regional body fat and lean tissue distribution in perimenopausal women. We hypothesized that the 24-week intake of SPI+ by perimenopausal women would attenuate the loss of waist, hip, and thigh lean mass and lessen the shift from the gynoid RFD pattern to the CVD-promoting android RFD pattern. Because RFD has been associated with glucose and insulin homeostasis, 1,17 estrogen deficiency, 18 and insulin-like growth factor I (IGF-I), 19,20 we additionally hypothesized that the effects of SPI+ on regional body composition may be associated with circulating concentrations of glucose, insulin, IGF-I, IGF binding protein-3 (IGFBP-3), or estrogens.

From the 1Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa; the 2Department of Food Science & Human Nutrition, Human Metabolic Unit, Center for Designing Foods to Improve Nutrition, and the Departments of 3Statistics and of 4Health and Human Performance, Iowa State University, Ames, Iowa; and the 5Department of Human Nutrition & Food Science, California State University at Pomona, Pomona, California.

Journal Paper 19453 of the Iowa Agriculture and Home Economics Experiment Station, Ames, Iowa. Project 3602, supported by Hatch Act and State of Iowa funds, USDA/Special Grant, and Iowa State University Research Grant.

Address reprint requests to D. Lee Alekel, PhD, RD, 1127 Human Nutritional Sciences Building; Department of Food Science & Human Nutrition, Iowa State University, Ames, IA 50011-1120. E-mail:

©2003The North American Menopause Society