D. Lee Alekel

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.

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

ObjectiveMenopause-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−). DesignPerimenopausal 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. ResultsMean 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. ConclusionsGain 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.

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 ≤ 0.0001) in androidal fat mass was accounted for by weight (53.0%, P ≤ 0.0001), white blood cell (WBC) count (2.0%, P ≤ 0.0001), supplemental calcium (1.7%, P = 0.0004), years since menopause (1.1%, P = 0.0034), 25(OH)D (1.0%, P = 0.0051), and vegetable servings (0.6%, P = 0.027); 64% of variability (P ≤ 0.0001) in lean mass was accounted for by weight (63.1.%, P ≤ 0.0001), WBC count (1.4%, P = 0.0038), and 25(OH)D (1.0%, P = 0.013); 12% of variability (P ≤ 0.0001) in balance (right + left leg) was accounted for by age (3.8%, P = 0.0019), 25(OH)D (2.0%, P = 0.025), and WBC count (1.8%, P = 0.032); 14% of variability (P ≤ 0.0001) in handgrip strength (right + left) was accounted for by weight (9.3%, P ≤ 0.0001), 25(OH)D (2.4%, P = 0.013), WBC count (2.1%, P = 0.019), and age (1.6%, P = 0.044); and 22% of variability (P ≤ 0.0001) in torso strength was accounted for by site (15.0%, P ≤ 0.0001) and weight (4.6%, P = 0.0003). Conclusions: Serum 25(OH)D was the common contributor to physical fitness indices (androidal fat mass, lean mass, balance, handgrip strength) in healthy postmenopausal women.

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 </= 0.0001) of the variability in AndGynFM ratio by high-density lipoprotein cholesterol (HDL-C) (4.3%, p = 0.008), ferritin (4.9%, p = 0.005), HOMA (4.5%, p = 0.006), oxLDL (2.6%, p = 0.04), and PGF(2alpha) (3.0%, p = 0.025). CONCLUSIONS Our study suggests that reducing centralized fat mass and maintaining a favorable lipid profile, antioxidant status, and iron status all may be important in protecting postmenopausal women from atherosclerotic CVD.

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 &agr;, interleukin-6, and interleukin-1&bgr; 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 ≤ 0.0001) was accounted for by androidal fat mass (16.1%, P ≤ 0.0001), white blood cells (5.6%, P ≤ 0.0001), and age (2.3%, P = 0.0045). Regression analyses revealed that 30% of the variability in fibrinogen (F = 24.5, P ≤ 0.0001) was accounted for by white blood cells (3.1%, P = 0.0015), hip fat mass (2.2%, P = 0.0081), years since menopause (0.9%, P = 0.082), and geographic site (P ≤ 0.0001). Our results indicated that androidal fat mass and hip fat mass contributed to C-reactive protein and fibrinogen, respectively, whereas we found no association between whole-body or regional fat measures and cytokines. Conclusion:Further study is warranted to determine the responsiveness of these acute-phase proteins and cytokines to loss of body fat through exercise and dietary intervention in postmenopausal 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.

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.

Breast Cancer Risk Factors in Two Distinct Ethnic Groups: Indian and Pakistani vs. American Premenopausal Women

Asian Indians from the Indian subcontinent have low rates of breast cancer, but studies on breast cancer risk factors in Indian and Pakistani women living in the United States are lacking. This study contrasted breast cancer risk factors [serum total 17 beta-estradiol (E2), sex hormone-binding globulin-bound E2, available E2, estrone (E1), and dehydroepiandrosterone sulfate, reproductive history, family history of cancer, body composition/size, dietary intake, physical activity, and excretion of isoflavones] between two distinct ethnic groups of premenopausal women residing in the United States. We also determined the contribution of these and other factors to the variability of each sex hormone. Distributions of values for serum total E2, available E2, and sex hormone-binding globulin-bound E2 (%) were greater (p < 0.005) in American (n = 47) than in Indian and Pakistani (n = 47) women. Multiple regression analysis indicated that 26% of the variability (p < or = 0.0001) in serum E2 was accounted for by the ratio of total cholesterol to high-density-lipoprotein cholesterol, length of time in the United States, and saturated fat intake, whereas less (17%) variability was accounted for by available E2 (representing free E2 + albumin-bound E2), contributed by the ratio of total cholesterol to high-density-lipoprotein cholesterol and saturated fat intake. Five variables accounted for 31% of the variability (p < or = 0.0001) in E1. The major finding of this study was that circulating sex hormone concentrations were determined more by environmental factors than by ethnicity, which was not a significant contributor to any of the serum hormones.

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.

Impact of Protein Supplements on Muscle Recovery After Exercise-induced Muscle Soreness

The intent of this study was to determine whether nutritional supplements [protein (0.4 g·kg −1 ) vs. carbohydrate (0.4 g·kg −1 ) vs. placebo] would affect muscle recovery differently after eccentric exercise-induced muscle soreness in untrained healthy young men (n = 21) aged 20-28 years. During this double-blind randomized block study design, each subject completed three, 3-day trials (separated by = 2 weeks), identical except for treatment, with each subject serving as his own control. Trials began with a bout of right-leg eccentric exercise (Biodex), followed directly by treatment. At 0 (baseline), 24 and 48 hours, data were collected: creatine phosphokinase from pre-exercise blood samples, subjective muscle soreness questions, and strength tests (power, torque, work). ANOVA indicated that exercise caused mild muscle damage, as evidenced by an overall day effect ( p = 0.0001) for muscle soreness, with the lowest median values (0-10 scale) on day 1 (0.7), increasing ( p = 0.0001) on day 2 (3.2), and remaining elevated on day 3 (3.4). We also noted an overall day effect ( p = 0.0001) for creatine phosphokinase, with the lowest median values on day 1 (136 U·L-1), increasing ( p = 0.0001) on day 2 (235 U·L-1), and remaining elevated on day 3 (189 U·L-1). ANOVA revealed no significant treatment effect on indicators of soreness or damage during recovery. Our results indicated that protein or carbohydrate supplement after exercise that caused mild muscle damage did not facilitate muscle recovery in adequately nourished, healthy young men.