Molecular Transducers of Physical Activity Consortium (MoTrPAC): Human Studies Design and Protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. While there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multi-center study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a pre-clinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 weeks of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 weeks. The adult component also includes recruitment of highly active endurance trained or resistance trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.

Soy Isoflavones for Reducing Bone Loss Study: effects of a 3-year trial on hormones, adverse events, and endometrial thickness in postmenopausal women.

OBJECTIVE: This study aims to assess the overall safety and potential endometrium-stimulating effects of soy isoflavone tablets consumed (3 y) by postmenopausal women and to determine endometrial thickness response to treatment among compliant women, taking into account hormone concentrations and other hypothesized modifying factors. METHODS: We randomized healthy postmenopausal women (aged 45.8-65.0 y) to placebo control or two doses (80 or 120 mg/d) of soy isoflavones at two sites. We used intent-to-treat analysis (N = 224) and compliant analysis (>95%; N = 208) to assess circulating hormone concentrations, adverse events, and endometrial thickness (via transvaginal ultrasound). RESULTS: Median values for endometrial thickness (mm) declined from baseline through 36 months. Nonparametric analysis of variance for treatment differences among groups showed no differences in absolute (or percentage of change) endometrial thickness (χ(2) P ranged from 0.12 to 0.69) or in circulating hormones at any time point. A greater number of adverse events in the genitourinary system (P = 0.005) were noted in the 80 mg/day group compared with the 120 mg/day group, whereas other systems showed no treatment effects. The model predicting endometrial thickness response (using natural logarithm) to treatment among compliant women across time points was significant (P ≤ 0.0001), indicating that estrogen exposure (P = 0.0013), plasma 17ß-estradiol (P = 0.0086), and alcohol intake (P = 0.023) contributed significantly to the response. Neither the 80 mg/day dose (P = 0.57) nor the 120 mg/day dose (P = 0.43) exerted an effect on endometrial thickness across time. CONCLUSIONS: Our randomized controlled trial verifies the long-term overall safety of soy isoflavone tablet intake by postmenopausal women who display excellent compliance. We find no evidence of treatment effects on endometrial thickness, adverse events, or circulating hormone concentrations, most notably thyroid function, across a 3-year period.

The effect of soy protein beverages on serum cell adhesion molecule concentrations in prehypertensive/stage 1 hypertensive individuals.

OBJECTIVE: Prehypertensive and hypertensive individuals are at increased risk of atherosclerotic cardiovascular disease (CVD), in part because hypertension contributes to endothelial dysfunction and increased cell adhesion molecule expression. Soy protein and isoflavones may favorably alter CVD risk factors, and hence the aim of this study was to determine whether intake of cow's milk compared with soy beverage prepared from whole soy bean (WSB) or soy protein isolate (SPI) would lower soluble cell adhesion molecule concentrations as a means of decreasing CVD risk. METHODS: We enrolled healthy prehypertensive/stage 1 hypertensive men (n = 60; 18-63 years) and premenopausal women (n = 8; 20-48 years). Participants were randomized to 1 of 3 groups for 8 weeks: cow's milk (600 mL/d), SPI beverage (840 mL/d; 30.1 mg total isoflavones/d), or WSB beverage (840 mL/d; 91.4 mg total isoflavones/d). We measured soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and endothelial-leukocyte adhesion molecule-1 (E-selectin) concentrations at baseline and week 8. RESULTS: Soluble CAM concentrations were not altered by treatment and did not differ between prehypertensive and hypertensive participants. However, analysis of variance indicated a treatment × gender interaction (gender effect) for ICAM-1 (p = 0.0037) but not for E-selectin (p = 0.067) or VCAM-1 (p = 0.16). Men had higher concentrations of ICAM-1 and E-selectin, respectively, at baseline (p = 0.0071, p = 0.049) and week 8 (p = 0.0054, p = 0.038) than women did. CONCLUSION: Neither intake of cow's milk nor soy beverage for 8 weeks altered soluble CAM concentrations in prehypertensive/stage 1 hypertensive individuals, suggesting that neither type of beverage diminished atherosclerotic CVD risk in mildly hypertensive individuals by way of improving circulating CAM concentrations.

Flavonoid intake and bone health.

Flavonoids, found in a wide diversity of plant foods from fruits and vegetables, herbs and spices, essential oils, and beverages, have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D. Recent epidemiological studies show flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption. Bioactive flavonoids are being assessed for properties beyond their chemical antioxidant capacity, including anti-inflammatory actions. Some have been reported to enhance bone formation and to inhibit bone resorption through their action on cell signaling pathways that influence osteoblast and osteoclast differentiation. Future research is needed to determine which of the flavonoids and their metabolites are most effective and at what dose, as well as the mechanism of modulating cellular events, in order to set priorities for clinical trials.

The effect of soy food intake on mineral status in premenopausal women.

BACKGROUND: Soy foods have been substituted for meat in recent years because of proposed health benefits. Research indicates, however, that soy protein and phytate in soy products inhibit the absorption of divalent cations. METHODS: Our study was primarily designed to determine the effect of consuming two to three servings per day of soy foods, providing ∼19 g protein and ∼36 mg isoflavones, on iron and zinc status in premenopausal women during a 10-weeks period. As secondary outcomes, we also tested the effect of soy foods on biochemical markers of bone and thyroid hormones. Nonsmoking women (18-28 years) without chronic disease, anemia, pregnancy, or irregular menstrual cycles were randomly assigned to either the soy food (SF, n=31) or animal food (AF, n=32) group. Blood and urine samples and 3-day dietary records were collected at baseline and postintervention. RESULTS: At baseline, iron and zinc status, bone markers, and thyroid hormones were not different between groups. After intervention, no significant changes were observed in hemoglobin, transferrin saturation, serum iron, ferritin, or transferrin receptor (TFR) concentrations. Plasma zinc, but not serum alkaline phosphatase, significantly decreased in both groups (-0.8 µmol/L). The change in bone-specific alkaline phosphatase was significant between SF (1.5 U/L) and AF (-0.7 U/L) groups. No significant changes were observed in bone resorption, thyroid-stimulating hormone (TSH), or free thyroxine after soy food intake. CONCLUSIONS: Incorporating ∼19 g soy protein from soy foods for 10 weeks had no significant effect on iron or zinc status, bone resorption or formation, or thyroid hormone status in premenopausal women.

The soy isoflavones for reducing bone loss study: 3-yr effects on pQCT bone mineral density and strength measures in postmenopausal women.

Soy isoflavones exert inconsistent bone density-preserving effects, but the bone strength-preserving effects in humans are unknown. Our double-blind randomized controlled trial examined 2 soy isoflavone doses (80 or 120mg/d) vs placebo tablets on volumetric bone mineral density (vBMD) and strength (by means of peripheral quantitative computed tomography) in healthy postmenopausal women (46-63yr). We measured 3-yr changes in cortical BMD (CtBMD), cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength-strain index (SSI) at 1/3 midshaft femur (N=171), and trabecular BMD (TbBMD), PC, and SSI at 4% distal tibia (N=162). We found no treatment effect on femur CtThk, PC, or EC, or tibia TbBMD or PC. The strongest predictors (negative) of tibia TbBMD and SSI and femur CtBMD were timepoint and bone resorption; whole-body fat mass was protective of SSI. As time since last menstrual period (TLMP) increased (p=0.012), 120-mg/d dose was protective of CtBMD. The strongest predictors of femur SSI were timepoint, bone resorption, and TLMP (protective). Isoflavone tablets were negative predictors of SSI, but 80-mg/d dose became protective as bone turnover increased (p=0.011). Soy isoflavone treatment for 3yr was modestly beneficial for midshaft femur vBMD as TLMP increased and for midshaft femur SSI as bone turnover increased.

Appetitive hormones, but not isoflavone tablets, influence overall and central adiposity in healthy postmenopausal women.

OBJECTIVE: One of the multiple health benefits of soy protein or its isoflavones may be their purported favorable effect on body composition. We examined the effect of isoflavones extracted from soy protein on overall and regional body composition, taking into account appetitive hormones as potential mediators, as well as the direct effect on appetitive hormones. METHODS: This randomized, double-blind, placebo-controlled multicenter trial included 229 healthy postmenopausal women (age, 45.8-65 y; body mass index, 24.9 +/- 3.0 kg/m) who consumed placebo or soy isoflavone (80 or 120 mg/d) tablets for 12 months. We used intent-to-treat analysis to examine changes in body composition (whole-body lean mass, whole-body fat mass, androidal fat mass, and androidal-to-gynoidal fat mass ratio) and appetitive hormones (insulin, leptin, ghrelin, and adiponectin) in response to treatment. RESULTS: Repeated-measures analysis of variance indicated that soy isoflavone treatment did not exert a significant effect on body composition measures (P value from 0.36 to 0.79) or appetitive hormone concentrations; the inclusion of covariates in statistical models did not alter these results. Independently of treatment, leptin and ghrelin related inversely to each body composition measure (P values from 0.044 to < or = 0.0001). Adiponectin related inversely to all fat measures (P values from 0.0004 to <0.0001). Time since last menstrual period related directly to all fat measures (P values from 0.06 to 0.0055). Dietary fat contributed to whole-body (P = 0.028) and androidal (P = 0.017) fat mass. CONCLUSIONS: Our findings do not support a favorable effect of soy isoflavone tablets on body composition in healthy postmenopausal women.

The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women.

BACKGROUND: Our previous study indicated that soy protein with isoflavones lessened lumbar spine bone loss in midlife women. OBJECTIVE: We examined the efficacy of isoflavones (extracted from soy protein) on bone mineral density (BMD) in nonosteoporotic postmenopausal women. We hypothesized that isoflavone tablets would spare BMD, with biological (age, body weight, serum 25-hydroxyvitamin D) and lifestyle (physical activity, dietary intake) factors modulating BMD loss. DESIGN: Our double-blind, randomized controlled trial (36 mo) included healthy postmenopausal women (aged 45.8-65.0 y) with intent-to-treat (n = 224) and compliant (n = 208) analyses. Treatment groups consisted of a placebo control group and 2 soy isoflavone groups (80 compared with 120 mg/d); women received 500 mg calcium and 600 IU vitamin D(3). Outcomes included lumbar spine, total proximal femur, femoral neck, and whole-body BMD. RESULTS: Analysis of variance for intent-to-treat and compliant (> or =80%) models, respectively, showed no treatment effect for spine (P = 0.46, P = 0.21), femur (P = 0.86, P = 0.46), neck (P = 0.17, P = 0.14), or whole-body (P = 0.86, P = 0.78) BMD. From baseline to 36 mo, BMD declined regardless of treatment. In intent-to-treat and compliant models, respectively, BMD decreases were as follows: spine (-2.08%, -1.99%), femur (-1.43%, -1.38%), neck (-2.56%, -2.51%), and whole body (-1.66%, -1.62%). Regression analysis (compliant model) indicated that age, whole-body fat mass, and bone resorption were common predictors of BMD change. After adjustment for these factors, 120 mg (compared with placebo) was protective (P = 0.024) for neck BMD. We observed no treatment effect on adverse events, endometrial thickness, or bone markers. CONCLUSION: Our results do not show a bone-sparing effect of extracted soy isoflavones, except for a modest effect at the femoral neck. This trial was registered at clinicaltrials.gov as NCT00043745.

Serum 25-hydroxyvitamin D is related to indicators of overall physical fitness in healthy postmenopausal women.

OBJECTIVE: Inadequate vitamin D status is related to increased adiposity, risk of falls, and muscle weakness, particularly in older people. We hypothesized that serum 25-hydroxyvitamin D [25(OH)D] is related to physical fitness indices (androidal fat, whole body lean mass, balance, strength) in healthy postmenopausal women. METHODS: Covariates for fitness indices included age or years since menopause, weight, 25(OH)D, energy expenditure, and calcium intake. Overall and regional (androidal fat mass = waist + hip fat) body composition was assessed (N = 242) via dual-energy x-ray absorptiometry. RESULTS: Regression analyses revealed that 71% of variability (P

Association of oxidative stress, iron, and centralized fat mass in healthy postmenopausal women.

OBJECTIVE: Centralized adiposity, insulin resistance, excess iron, and elevated oxidative stress place postmenopausal women at risk for atherosclerotic cardiovascular disease (CVD). The objective of this study was to determine the relationship among excess iron, oxidative stress, and centralized fat mass in healthy postmenopausal women. METHODS: The parent project recruited healthy women for a randomized, double-blind, clinical trial designed to examine the effect of soy isoflavones on bone. At baseline (n = 122), we measured three antioxidant enzymes, iron status indices (serum ferritin among others), oxidative stress indices (oxidized low-density lipoprotein [oxLDL], urinary isoprostanes [PGF(2alpha)], protein carbonyls, DNA damage), and waist, hip, and thigh fat mass using dual-energy x-ray absorptiometry (DXA). We calculated insulin resistance using the homeostasis model assessment (HOMA). Multiple regression analysis was used to determine the CVD risk factors that contributed to oxidative stress and centralized fat mass (waist + hip/thigh = AndGynFM ratio). RESULTS: Almost 14% (p < 0.0005) of the variability in oxLDL was accounted for by AndGynFM ratio (6.1%, p < 0.0005), age (4.0%, p = 0.012), and serum iron (2.8%, p = 0.053). Similarly, 16% (p < 0.0001) of the variability in PGF(2alpha) was accounted for by the AndGynFM ratio (4.8%, p = 0.011), HOMA (3.9%, p = 0.021), and serum iron (2.7%, p = 0.054). We accounted for 33% (p

Centrally located body fat is related to appetitive hormones in healthy postmenopausal women.

OBJECTIVE: Body composition and energy homeostasis are thought to affect the appetitive hormones: adiponectin, leptin, insulin, and ghrelin. This study examined whether centrally located fat and/or overall adiposity were related to these appetitive hormones in healthy postmenopausal women. DESIGN: Overall and regional body composition was assessed by dual-energy X ray absorptiometry in relation to plasma adiponectin, serum leptin, serum insulin, and plasma ghrelin in 242 postmenopausal women. RESULTS: Regression analyses revealed that the androidal-to-gynoidal fat mass ratio (18.0%), age (3.2%), and white blood cell count (1.8%) accounted for 28% of the variability in adiponectin (F=22.2; P<0.0001); androidal (waist+hip) fat mass (66.0%), androidal fat mass(2) (6.2%), whole-body lean mass (2.2%), and age (0.8%) accounted for 69% of the variability in leptin (F=102.5; P<0.0001). Regression analyses revealed that sagittal abdominal diameter (8.4%), glucose (5.4%), white blood cell count (2.6%), and dietary omega-3 fatty acids (2.0%) accounted for 32% of the variability in insulin (F=20.8; P<0.0001); waist circumference (12.7%), hip lean mass (2.0%), and white blood cell count (1.9%) accounted for 26% of the variability in ghrelin (F=20.7; P<0.0001). Our results indicated that centralized fat mass was the primary contributor to these appetitive hormones in healthy postmenopausal women. CONCLUSION: Since central adiposity in postmenopausal women was related to appetitive hormones, minimizing weight gain during the menopausal transition may optimize appetitive hormones, thereby facilitating appetite control and weight maintenance.

Centrally located body fat is related to inflammatory markers in healthy postmenopausal women.

OBJECTIVE: C-reactive protein and fibrinogen are established atherosclerotic cardiovascular disease risk factors. These acute-phase proteins and the proinflammatory cytokines tumor necrosis factor alpha, interleukin-6, and interleukin-1beta may be elevated in obesity and with menopause. The purpose of this multicenter study was to identify whether centrally located fat and/or overall adiposity were related to these inflammatory markers in healthy postmenopausal women. DESIGN: We used dual-energy x-ray absorptiometry to assess overall and regional body composition (fat mass in particular) in 242 postmenopausal women in relation to plasma fibrinogen, serum C-reactive protein, and these proinflammatory cytokines. RESULTS: Multiple regression analyses revealed that 36% of the variability in C-reactive protein (F = 32.4, P

Quantifying leisure physical activity and its relation to bone density and strength.

PURPOSE: Compare three published methods of quantifying physical activity (total activity, peak strain, and bone-loading exposure (BLE) scores) and identify their associations with areal bone mineral density (aBMD), volumetric BMD (vBMD), and bone strength. METHODS: Postmenopausal women (N = 239; mean age: 53.8 yr) from Iowa (ISU) and California (UCD) completed the Paffenbarger Physical Activity Questionnaire, which was scored with each method. Dual energy x-ray absorptiometry assessed aBMD at the spine, hip, and femoral neck, and peripheral quantitative computed tomography (pQCT) measured vBMD and bone strength properties at the distal tibia and midshaft femur. RESULTS: UCD women had higher total activity scores and hours per week of leisure activity. All scoring methods were correlated with each other. No method was associated with aBMD. Peak strain score was negatively associated with polar moment of inertia and strength-strain index at the tibia, and total activity score was positively associated with cortical area and thickness at the femur. Separating by geographic site, the peak strain and hip BLE scores were negatively associated with pQCT measures at the tibia and femur among ISU subjects. Among UCD women, no method was significantly associated with any tibia measure, but total activity score was positively associated with measures at the femur (P < 0.05 for all associations). CONCLUSION: Given the significantly greater hours per week of leisure activity done by UCD subjects, duration may be an important determinant of the effect physical activity has on bone. The positive association between leisure physical activity (assessed by the total activity score) and cortical bone measures in postmenopausal women may indicate a lifestyle factor that can help offset age-related bone loss.

Relationship of circulating total homocysteine and C-reactive protein to trabecular bone in postmenopausal women.

Homocysteine (Hcy) and C-reactive protein (CRP) are novel risk factors for osteoporosis. The purpose of this analysis was to determine the relationship of Hcy and CRP to volumetric trabecular bone, but also to assess their relationship to areal composite bone in healthy postmenopausal women (N=184). We used peripheral quantitative computed tomography to assess volumetric bone at the distal tibia and dual-energy X-ray absorptiometry to assess areal composite bone at the proximal femur and lumbar spine. Multiple regression revealed that 22% of the variability in trabecular bone mineral content (F=9.59, p

Effects of soy isoflavones and phytate on homocysteine, C-reactive protein, and iron status in postmenopausal women.

BACKGROUND: Soy protein or its components may protect against the atherosclerotic cardiovascular disease (CVD) risk factors total homocysteine (tHcy), C-reactive protein (CRP), and excess body iron, which generally increase with menopause. OBJECTIVE: The primary objective of this study was to determine the independent effect of the soy protein components isoflavones and phytate on CVD risk factors in postmenopausal women. The secondary objective was to identify factors [blood lipids, oxidative stress indexes, serum ferritin, plasma folate, plasma vitamin B-12, and body mass index (BMI)] contributing to tHcy and CRP concentrations. DESIGN: In a double-blind, 6-wk study, 55 postmenopausal women aged 47-72 y were randomly assigned to 1 of 4 soy protein (40 g/d) isolate treatments: native phytate and native isoflavone (n = 14), native phytate and low isoflavone (n = 13), low phytate and native isoflavone (n = 14), or low phytate and low isoflavone (n = 14). We measured iron indexes, tHcy, CRP, and BMI. RESULTS: Soy protein with native phytate significantly reduced tHcy (P = 0.017), transferrin saturation (P = 0.027), and ferritin (P = 0.029), whereas soy protein with native isoflavones had no effect on any variables. At baseline, BMI was highly correlated with tHcy (r = 0.39, P = 0.003) and CRP (r = 0.55, P < 0.0001), whereas HDL cholesterol was correlated with CRP (r = -0.30, P = 0.02). Multiple regression analysis showed that LDL cholesterol and BMI contributed significantly (R2= 19.9%, P = 0.003) to the overall variance in tHcy. CONCLUSION: Consuming phytate-rich foods and maintaining a healthy weight may reduce atherosclerotic CVD risk factors in postmenopausal women.

Body composition, dietary intake, and iron status of female collegiate swimmers and divers.

This study determined the effect of training on body composition, dietary intake, and iron status of eumenorrheic female collegiate swimmers (n = 18) and divers (n = 6) preseason and after 16 wk of training. Athletes trained on dryland (resistance, strength, flexibility) 3 d/wk, 1.5 h/d and in-water 6 d/wk, nine, 2-h sessions per week (6400 to 10,000 kJ/d). Body-mass index (kg/m2; P = 0.05), waist and hip circumferences (P < or = 0.0001), whole body fat mass (P = 0.0002), and percentage body fat (P < or = 0.0001) decreased, whereas lean mass increased (P = 0.028). Using dual-energy X-ray absorptiometry, we found no change in regional lean mass, but fat decreased at the waist (P = 0.0002), hip (P = 0.0002), and thigh (P = 0.002). Energy intake (10,061 +/- 3617 kJ/d) did not change, but dietary quality improved with training, as reflected by increased intakes of fiber (P = 0.036), iron (P = 0.015), vitamin C (P = 0.029), vitamin B-6 (P = 0.032), and fruit (P = 0.003). Iron status improved as reflected by slight increases in hemoglobin (P = 0.046) and hematocrit (P = 0.014) and decreases in serum transferrin receptor (P < or = 0.0001). Studies are needed to further evaluate body composition and iron status in relation to dietary intake in female swimmers.

Blood lipid and oxidative stress responses to soy protein with isoflavones and phytic acid in postmenopausal women.

BACKGROUND: Postmenopausal women are at risk of cardiovascular disease (CVD) as a result of unfavorable blood lipid profiles and increased oxidative stress. Soy protein consumption may help protect against these risk factors. OBJECTIVE: Our objective was to ascertain the effect of the soy protein components isoflavones and phytate on CVD risk in postmenopausal women. DESIGN: In a double-blind 6-wk study, 55 postmenopausal women were randomly assigned to 1 of 4 treatments with soy protein (40 g/d) isolate (SPI): low phytate/low isoflavone (LP/LI); normal phytate/low isoflavone (NP/LI); low phytate/normal isoflavone (LP/NI); or normal phytate/normal isoflavone (NP/NI). Blood lipids (total, LDL, and HDL cholesterol and triacylglycerol) and oxidative stress indexes (protein carbonyls, oxidized LDLs, and 8-iso-prostaglandin-F(2alpha)) were measured at baseline and 6 wk. RESULTS: The oxidative stress indexes were not significantly affected by either phytate or isoflavones. Phytate treatment had a minimal but nonsignificant effect in reducing protein carbonyls and 8-iso-prostaglandin-F(2alpha); the reductions were 6-8% and 4-6% in the NP/LI and NP/NI groups and 1-4% and 3-4% in the LP/LI and LP/NI groups, respectively. Similarly, circulating lipids were not significantly affected by either phytate or isoflavones. The decline in total (6%-7% compared with 2%-4%) and LDL (10%-11% compared with 3%-7%) cholesterol did not differ significantly between the normal- and low-isoflavone groups, respectively. CONCLUSION: In postmenopausal women, neither phytate nor isoflavones in SPI have a significant effect of reducing oxidative damage or favorably altering blood lipids.

Skeletal benefits of soy isoflavones: a review of the clinical trial and epidemiologic data.

PURPOSE OF REVIEW: Osteoporosis is a worldwide problem of immense magnitude that is expected to worsen in many countries with aging populations. Consequently, there is a need to identify ways to reduce the risk of developing this disease. This is especially true in light of clinical trial data showing the long-term harm of conventional hormone therapy outweighs the benefits. It is well established that many dietary components impact the skeletal system; in this regard there is particular interest in the possible skeletal benefits of soybean isoflavones. The purpose of this review is to evaluate the clinical and epidemiologic studies relevant to the hypothesis that isoflavones promote bone health. RESULTS: Fifteen clinical trials were identified that examined the effects of isoflavones or isoflavone-rich soy protein on bone mineral density. Most trials were conducted for 1 year or less and involved relatively few (<30) participants per group. The findings from these studies are inconsistent but generally suggest that isoflavones reduce bone loss in younger postmenopausal women. Similarly, the limited epidemiologic data generally show that among Asian populations isoflavone intake is associated with higher bone mineral density. The clinical data suggest that approximately 80 mg/day isoflavones are needed to derive skeletal benefits whereas the epidemiologic data suggest lower amounts are efficacious. SUMMARY: Until more definite data are available, although soy foods and isoflavones can not be viewed as substitutes for established anti-osteoporotic medications health professionals can feel justified in encouraging postmenopausal women concerned about bone health to incorporate soyfoods into their diet.

Rapid gut transit time and slow fecal isoflavone disappearance phenotype are associated with greater genistein bioavailability in women.

The bioavailability of soybean isoflavones varies widely among individuals due to many factors, including activities of gut microflora. To characterize factors that affect fecal isoflavone disappearance phenotype and isoflavone bioavailability in women, 35 Asian and 33 Caucasian women, 18-43 y of age, provided fecal samples for anaerobic incubation with isoflavones in vitro at two times 5 mo apart (Phases I and II). Diet, physical activity and health history were investigated at these times. A single dose of soymilk powder [1.2 mg (4.57 micromol) total isoflavone/kg body] was given to all subjects with breakfast in phase II. Daidzein and genistein from fecal incubations, urine and fecal samples were measured by reverse-phase HPLC. Three significantly different daidzein and two genistein disappearance phenotypes were identified from fecal isoflavone incubations. More Asians than Caucasians were identified within the high daidzein disappearance phenotype. Caucasians and Asians differed significantly in daily intake of red meat (0.3 +/- 0.1 vs. 1.0 +/- 0.1 servings/d), dairy foods (2.9 +/- 0.2 vs. 1.2 +/- 0.2 servings/d) and insoluble dietary fiber (3.6 +/- 0.3 vs. 1.4 +/- 0.3 g). BMI, maximal oxygen uptake (VO(2 max)) and physical activity level were significantly greater in Caucasians than in Asians. Asian subjects of the low genistein disappearance phenotype had more rapid gut transit time (GTT) and greater isoflavone bioavailability as reflected in urinary genistein excretion than did Asians of the high genistein disappearance phenotype (GTT, 40 +/- 8 vs. 63 +/- 5 h; 11.0 +/- 2.7 vs. 4.0 +/- 1.7% of ingested genistein excreted in urine). Caucasians of both genistein disappearance phenotypes had longer GTT than did Asian subjects (84 +/- 5 vs. 56 +/- 6 h) and resembled Asians of the high genistein disappearance phenotype in genistein bioavailability. Relatively rapid GTT coupled with a low fecal isoflavone disappearance phenotype as occurred in Asian but not Caucasian subjects produced greater genistein bioavailability, as reflected in urinary genistein excretion.