High-isoflavone Soy Research Articles

Soy isoflavone ameliorated the alterations in circulating adipokines and microRNAs of mice fed a high-fat diet.

Soy protein, containing isoflavones and bioactive peptides, is shown to have anti-obesity effects, but the main contributor and underlying mechanisms remain unclear. Recent studies have demonstrated that circulating microRNAs (miRNAs) act as important mediators in obesity and metabolic processes. In this study, we investigated whether soy protein components have distinctive effects on adiposity and circulating miRNA profiles in obese mice. C57BL/6J mice were divided into 4 groups, and each group was fed with a control, high-fat (HF), HF with low-isoflavone soy protein (HF/S), or HF with high-isoflavone soy protein (HF/SI) diet for 16 weeks. In the HF/SI group, changes in the serum adipokine levels, adipocyte diameter, and the number of crown-like structures (CLS) were alleviated compared to those of the HF group. In the HF/S group, the number of CLS was reduced. Decreases in body and adipose tissue weights were not observed in both HF/S and HF/SI groups. Through microarray analysis of serum miRNAs, we identified 23 differentially expressed miRNAs (DEMs) among the groups. The levels of most circulating DEMs were correlated with body weight, serum biochemical parameters, and adipose tissue histology. Functional analysis of predicted target genes of DEMs from both HF vs. CON and HF/S vs. CON comparisons revealed several cancer-related pathways. Only 2 DEMs were identified in the HF/SI vs. CON comparison. In conclusion, the present study confirmed that soy isoflavones are the main contributor to the health-beneficial effects of soy protein in diet-induced obesity. Notably, the extent of serum miRNA dysregulation coincided with obesity and altered the circulating adipokine levels. These findings provide additional insights into the role of soy protein in the regulation of circulating miRNAs in diet-induced obesity. Further work is required to validate the proposed functions of miRNAs in target tissues.

Both diet and Helicobacter pylori infection contribute to atherosclerosis in pre- and postmenopausal cynomolgus monkeys.

A number of viruses and bacterial species have been implicated as contributors to atherosclerosis, potentially providing novel pathways for prevention. Epidemiological studies examining the association between Helicobacter pylori and cardiovascular disease have yielded variable results and no studies have been conducted in nonhuman primates. In this investigation, we examined the relationship between H. pylori infection and atherosclerosis development in socially housed, pre- and postmenopausal cynomolgus macaques consuming human-like diets. Ninety-four premenopausal cynomolgus monkeys (Macaca fascicularis) were fed for 36 months an atherogenic diet deriving its protein from either casein lactalbumin(CL) or high isoflavone soy (SOY). Animals were then ovariectomized and fed either the same or the alternate diet for an additional 36 months. Iliac artery biopsies were obtained at the time of ovariectomy and iliac and coronary artery sections were examined at the end of the study. Evidence of H. pylori infection was found in 64% of the monkeys and 46% of animals had live H. pylori within coronary atheromas as determined by mRNA-specific in situ hybridization. There was a significant linear relationship between the densities of gastric and atheroma organisms. Helicobactor pylori infection correlated with increased intimal plaque area and thickness at both the premenopausal and postmenopausal time points and regardless of diet (p< 0.01), although animals consuming the SOY diet throughout had the least amount of atherosclerosis. Additionally, plasma lipid profiles, intimal collagen accumulation, ICAM-1, and plaque macrophage densities were adversely affected by H. pylori infection among animals consuming the CL diet, while the SOY diet had the opposite effect. Plaque measurements were more highly associated with the densities of cagA-positive H. pylori within coronary atheromas than with the densities of gastric organisms, whereas plasma lipid changes were associated with H. pylori infection, but not cagA status. This study provides strong evidence that live H. pylori infects atheromas, exacerbates atherosclerotic plaque development, and alters plasma lipid profiles independently of diet or hormonal status. Finally, socially subordinate animals relative to their dominant counterparts had a greater prevalence of H. pylori, suggesting a stress effect. The results indicate that early H. pylori eradication could prevent or delay development of cardiovascular disease.

Beneficial effects of soy supplementation on postmenopausal atherosclerosis are dependent on pretreatment stage of plaque progression.

The objective of this study was to use a well-established monkey model of atherosclerosis to determine how life stage and preexisting atherosclerosis influence the effectiveness of high-isoflavone soy diet in inhibiting progression of atherosclerosis. For 34 months, premenopausal monkeys were fed an atherogenic diet, with protein derived primarily from either animal sources (casein-lactalbumin [CL], n = 37) or high-isoflavone soy beans (Soy, n = 34). Animals were ovariectomized and randomized to groups fed the same diet (CL-CL, n = 20; Soy-Soy, n = 17) or an alternate diet (CL-Soy, n = 17; Soy-CL, n = 17) for an additional 34 months. At ovariectomy, the left common iliac artery was removed to determine the amount of premenopausal atherosclerosis. At necropsy, the right common iliac artery and coronary arteries were collected, and atherosclerosis extent was quantified. CL-CL condition was considered "control." Modeling Asian women who remain in Asia, monkeys fed soy protein both premenopausally and postmenopausally had a markedly reduced extent of coronary artery atherosclerosis relative to CL controls (P = 0.008). The subset of animals that modeled Asian women who migrate to a Western country (consuming soy premenopausally and CL postmenopausally) had increased progression of postmenopausal iliac artery atherosclerosis (P = 0.003) and was not protected against the development of coronary artery atherosclerosis relative to controls. Relevant to the administration of soy diets to postmenopausal Western women, monkeys fed CL premenopausally and switched to soy postmenopausally derived atheroprotective benefits only if they began the postmenopausal treatment period with relatively small (below the median) plaques. Relative to controls, this group (with small plaques at ovariectomy) had reduced progression of iliac atherosclerosis (P = 0.038) and smaller coronary artery plaques (P = 0.0001) that were less complicated (P = 0.05) relative to controls. The results suggest that significant atheroprotective benefits of dietary soy are derived from treatment that begins premenopausally and continues postmenopausally or from treatment that is started during early postmenopause (when plaques are still small).

Dietary soy protein induces hepatic lipogenic enzyme gene expression while suppressing hepatosteatosis in obese female Zucker rats bearing DMBA-initiated mammary tumors

Fatty liver is associated with obesity and breast cancer. We used an obese rat model of mammary cancer to examine whether hepatosteatosis is modifiable by diet and associated with altered expression of hepatic lipogenic enzyme genes, thyroid hormone system genes and cholesterol metabolism-related genes. Beginning at the age of 5weeks, lean and obese female Zucker rats were fed high-isoflavone soy protein- or casein (control protein)-containing diets. Rats were euthanized at 200days of age [corresponding to 147days after administration of carcinogen to induce mammary tumors; (Hakkak et al. in, Oncol Lett 2:29-36, 2011)]. Obese rats had a greater degree of liver steatosis than lean rats. Obese casein-fed rats had marked steatosis with small foci of mononuclear infiltration, whereas obese soy protein-fed rats had a significantly lower steatosis index. Comparisons between lean and obese casein-fed rats showed that obesity was associated with significant reductions in hepatic mRNA abundance for Glucose 6-Phosphate Dehydrogenase (G6PD), 6-Phosphogluconate Dehydrogenase (6PGD), Thyroid Receptor Alpha 1 (TRα1), Thyroid Receptor Beta 1 (TRβ1) and Iodothyronine Deiodinase 1 (DIO1). The soy protein diet was associated with increased expression of Fatty Acid Synthase (FASN), Malic Enzyme 1 (ME1), 6PGD, Sterol Regulatory Element Binding Protein-1c (SREBP-1c) and SREBP-2 genes in the livers of obese but not lean rats. Western blot analysis showed a significant induction of ME1 protein expression in the livers of obese, soy protein-fed rats, which paralleled the increased serum insulin level in this group. Long-term soy protein consumption can counter hepatic steatosis while coincidently promoting hepatic lipogenic gene expression, the latter likely a consequence of elevated serum insulin. We suggest that elevations in serum insulin, hepatic lipogenesis and cholesterol synthesis all contributed to the increased tumorigenesis previously observed for the obese, soy protein-fed rats.

Isoflavones: effects on bone health

Background There are many effects described, both experimental and clinical, that assess the relationship between isoflavones and bone. It has been hypothesized that isoflavones may have a positive effect on bone health.Objective To review the effects of isoflavones on biochemical markers of bone remodeling, bone density and bone quality, and finally on fracture incidence.Methods A systematic review was carried out of in vitro, animal, and human studies involving isoflavones and bone health. An electronic search was made, based on Internet search engines, MEDLINE (1966–June 2010) and the Cochrane Controlled Clinical Trials Register. This search was further supplemented by a hand-search of reference lists of selected review papers.Results After crossing-cleaning the reference lists, 737 studies dealing with isoflavones and bone were identified. Of these, 36 were considered selectable. From in vitro and animal studies, isoflavones appear to stimulate osteoblastic bone formation and inhibit osteoclastic bone resorption. Reviewed data show evidence of a beneficial effect of isoflavones on bone health in peri- and postmenopausal women when high-isoflavone soy protein is incorporated in the diet. Inconsistencies observed among data from different studies are related to differences in study design, the variety of soy sources of isoflavones, time of analysis, and the variability in the bioavailability and metabolism of isoflavones.Conclusions Most of the studies suggested a positive relationship between isoflavones and bone health. Further well-controlled, randomized, double-blind, clinical trials with a larger sample population, longer duration, and examination of various dosages are needed to better elucidate the inter-relationship between isoflavones and bone loss and to clarify whether isoflavones could prevent bone fractures.

Effects of high-isoflavone soy diet vs. casein protein diet and obesity on DMBA-induced mammary tumor development

Obesity and elevated serum insulin growth factor-1 (IGF-1) level are major risk factors in the development of breast cancer. We investigated the long-term effects of high-isoflavone soy intake and obesity on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumor development and on serum IGF-1 and binding protein (IGFBP-3) levels. Lean and obese female Zucker rats fed casein or high-isoflavone soy protein were orally gavaged at age 50 days with DMBA and sacrificed after 147 days. The majority of lean casein-fed rats (69%) developed mammary tumors compared to 50% in lean soy-fed rats (P=0.176). In the obese groups, 76% of soy-fed rats developed mammary tumors compared to 15% of obese casein-fed rats (P<0.001). At age 43 days, IGFBP-3 was increased in the lean soy-fed rats compared to the lean casein-fed rats (P<0.05). At age 99 days, soy- and obese casein-fed rats exhibited increased serum IGF-1 compared to the lean rats and this increase was maintained for the rest of the experiment (P<0.05). Obese rats fed casein exhibited increased IGFBP-3 levels (P<0.001). However, obese rats fed soy exhibited a significant decrease in IGFBP-3 levels compared to the lean soy-fed rats (P<0.001) and a significant decrease in IGFBP-3 levels compared to the obese casein-fed rats (P<0.001). At age 197 days, IGFBP-3 levels were increased in obese casein-and soy-fed rats (P<0.001). The results suggest that female Zucker rats fed casein diets are protected against DMBA-induced mammary tumors, which is not the case for those on high-isoflavone soy diet, and changes in the concentration of serum IGFBP-3 may contribute to the incidence of DMBA-induced mammary tumors.

Dietary soy protein benefit in experimental kidney disease is preserved after isoflavone depletion of diet

Soy diet ameliorates renal injury in the Han:SPRD-cy rat. The relative roles of protein, isoflavones and changes in polyunsaturated fatty acid (PUFA) status are not determined. We fed male Han:SPRD-cy heterozygotes casein (C), high isoflavone soy protein (HIS), alcohol-extracted low isoflavone soy protein (LIS) or mixed soy protein diet (MIS). LIS and MIS were associated with a small decrease in animal weight compared with HIS or C. Soy diets preserved normal renal function and reduced relative renal weight (10.9-14.6 g/kg, cf. 23.6, P < 0.001), scores for cystic change (0.168-0.239, cf. 0.386, P < 0.05), fibrosis (0.013-0.015, cf. 0.032, P < 0.05), tissue oxidized LDL content (0.012-0.021, cf. 0.048, P < 0.05), inflammation (8.5-12.9, cf. 31.2, P < 0.05) and epithelial cell proliferation (6.5-13.8, cf. 26.3, P < 0.05). In post hoc testing, LIS produced a greater reduction in relative renal weight, cystic change and epithelial proliferation, whereas HIS produced a significantly greater reduction in oxidized-LDL. Soy diets were associated with increased hepatic content of 18C PUFA (P < 0.001). LIS and HIS diets were associated with a small increase in body fat content (P < 0.001). Alcohol-extracted soy protein retains its major protective effects in this model with subtle differences attributable to isoflavones.

Impairment of ovarian function and associated health-related abnormalities are attributable to low social status in premenopausal monkeys and not mitigated by a high-isoflavone soy diet.

Psychological stress may impair premenopausal ovarian function and contribute to risk for chronic disease. Soy isoflavones may also influence ovarian function and affect health. Here, we report the effects of a psychological stressor (subordinate social status) and dietary soy on reproductive function and related health indices in female monkeys. We hypothesized that reproductive compromise and adverse health outcomes would be induced in subordinate when compared with dominant monkeys and be mitigated by exposure to soy. Subjects were 95 adult cynomolgus monkeys (Macaca fascicularis) housed in social groups of five or six. Animals consumed a soy-free, animal protein-based diet during an 8-month Baseline phase and then, during a 32-month Treatment phase, consumed either the baseline diet or an identical diet that substituted high-isoflavone soy protein for animal protein. Across more than 1200 menstrual cycles, subordinate monkeys consistently exhibited ovarian impairment [increased cycle length (P < 0.02) and variability (P < 0.02) and reduced levels of progesterone (P < 0.04) and estradiol (P < 0.04)]. Subordinate status was confirmed behaviorally and was associated with elevated cortisol (P < 0.04) and relative osteopenia (P < 0.05). Consumption of the soy diet had no significant effects. (i) Psychological stress adversely affects ovarian function and related health indices in a well-accepted animal model of women's health; (ii) Similar effects may extend to women experiencing reproductive impairment of psychogenic origin; (iii) soy protein and isoflavones neither exacerbate nor mitigate the effects of an adverse psychosocial environment; and (iv) this study was limited by an inability to investigate the genetic and developmental determinants of social status.

Soy protein isolates of varying isoflavone content do not adversely affect semen quality in healthy young men

To determine the effects of consumption of soy protein of varying isoflavone content on parameters of semen quality in healthy young men. Randomized crossover intervention. University campus. Healthy adult men (age 27.5 ± 5.67 years, body mass index 25.4 ± 3.14 kg/m(2)). Milk protein isolate (MPI), low-isoflavone soy protein isolate (low-iso SPI; 1.64 ± 0.19 mg isoflavones/day, expressed as aglycone equivalents), and high-isoflavone soy protein isolate (high-iso SPI; 61.7 ± 7.35 mg isoflavones/day, expressed as aglycone equivalents) for 57 days each separated by 28-day washout periods. Urinary isoflavones were measured from 24-hour urine samples collected on days 54-56 of each treatment period. Semen quality parameters (semen volume, sperm concentration, sperm count, sperm percent motility, total motile sperm count, sperm morphology) were measured from semen samples collected on days 1 and 57 of each treatment period. Urinary isoflavones were significantly higher after consumption of high-iso SPI compared with the low-iso SPI and MPI. Semen parameters, including semen volume, sperm concentration, sperm count, sperm percent motility, total motile sperm count, and sperm morphology, were not significantly affected by consumption of either low- or high-iso SPI compared with MPI. Consumption of soy protein of low or high isoflavone content does not adversely affect semen quality in a sample of healthy adult men.

Effects of Obesity, short‐term soy vs casein protein diet and DMBA on Liver CYP 1A1 and CYP 1B1 Expression in Ovariectomized Obese Zucker Rats

Obesity is a risk factor for post‐menopausal breast cancer development. We have shown that obesity increases DMBA‐induced mammary tumor development in intact and ovariectomized Zucker rats. Several data suggest that DMBA requires metabolic activation to exert its carcinogenic effects. The objective of this study was to investigate the effect of obesity and high‐isoflavone soy (high‐isof soy) vs casein diet on hepatic expression of CYP1A1 and CYP1B1 following DMBA treatment in obese and lean ovariectomized Zucker rats. Forty day‐old, ovariectomized obese (n=40) and lean (n=40), Zucker rats were administered a diet containing either casein or high‐isof soy protein isolate and 10 days later were orally gavaged with either with sesame oil (control) or with 65 mg/kg DMBA in sesame oil. All rats were sacrificed 24 hrs post‐DMBA treatment. Liver microsomes were prepared and CYP1A1 and CYP 1B1 expression was measured by Western blotting using goat anti‐mouse CYP1A1 and CYP1B1 antibodies. DMBA treatment significantly (p&lt;0.001) increased expression of CYP1A1 in lean and obese ovariectomized rats in both casein and high‐isof soy‐fed group compared to the oil control groups. High‐isof soy diet decreased (p&lt;0.001) CYP1A1 expression in DMBA treated lean rats compared to lean casein‐fed rats but CYP1A1 expression was increased (p&lt;0.001) by DMBA in obese soy‐fed rats compared to high‐isof soy‐fed lean rats. CYP1B1 expression was not affected by diet, obesity or DMBA. These data suggest that obesity can increase the expression of enzymes that are responsible for DMBA metabolism in the ovariectomized Zucker rat model. (Supported by Susan G. Komen Foundation and ABI to RH).

Dietary soy isoflavones increase insulin secretion and prevent the development of diabetic cataracts in streptozotocin-induced diabetic rats

Soy isoflavone-containing diets have been reported to be beneficial in diabetes. This present study investigated the hypoglycemic effects of isoflavones in streptozotocin (STZ)-induced diabetes. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 100 mg/kg STZ. Diabetic rats were then randomly divided into 3 groups and received a special diet supplemented with casein (control), low-isoflavone soy (LIS) protein, and high-isoflavone soy protein (HIS) for 8 weeks. Compared with the control or LIS groups, those rats on the HIS diet had significantly increased body weight and serum insulin levels and reduced serum glucose and methylglyoxal levels. Serum glutathione levels were also increased in rats given the HIS diet compared with those in the control or LIS (P < .01). Serum high-density lipoprotein cholesterol level was significantly higher in HIS-fed rats than that of the control or LIS rats (P < .05). More importantly, the death rate and incidence of cataracts in the diabetic rats were markedly decreased in the HIS group. In conclusion, ingestion of high-isoflavone soy protein not only lowers glucose levels but also reduces the incidence of cataracts in diabetic rats. The beneficial effects of soy isoflavones are attributed to increased insulin secretion, a better glycemic control, and antioxidant protection.

Increased Insulin Sensitivity and Changes in the Expression Profile of Key Insulin Regulatory Genes and Beta Cell Transcription Factors in Diabetic KKAy-Mice after Feeding with a Soy Bean Protein Rich Diet High in Isoflavone Content

High content isoflavone soy protein (SBP) (Abalon) has been found in animal studies to possess beneficial effects on a number of the characteristic features of the insulin resistance syndrome. The aim of this study was to investigate whether SBP exerts beneficial effects on metabolism in the diabetic KKAy-mouse. Furthermore, we investigated the long-term in vivo effect of SBP on the expression profile in islets of key insulin regulatory genes. Twenty KKAy-mice, aged 5 weeks, were divided into 2 groups and treated for 9 weeks with either (A) standard chow diet (control) or (B) chow + 50% SBP. Twenty normal C57BL-mice fed with standard chow diet served as nondiabetic controls (C). Blood samples were collected and analyzed before and after intervention. Gene expression was determined in islets by quantitative real-time RT-PCR and Affymetrix microarray. It was demonstrated that long-term treatment with SBP improves glucose homeostasis, increases insulin sensitivity, and lowers plasma triglycerides in diabetic KKAy-mice. SBP reduces fasting plasma glucose, insulin, triglycerides, and total cholesterol. Furthermore, SBP markedly changes the gene expression profile of key insulin regulatory genes GLUT2, GLUT3, Ins1, Ins2, IGF1, Beta2/Neurod1, cholecystokinin, and LDLr, and proliferative genes in islets isolated from KKAy-mice. After 9 weeks of treatment with SBP, plasma glucose and insulin homeostasis was normalized compared to start levels. The results indicate that SBP improves glucose and insulin sensitivity and up-regulates the expression of key insulin regulatory genes.

High isoflavone soy diet increases insulin secretion without decreasing insulin sensitivity in premenopausal nonhuman primates

Consuming soy and soy isoflavones has been shown to cause modest improvements in plasma lipids, lipoproteins, and indices of insulin sensitivity in postmenopausal women. The effect of soy on such end points is attributed often to estrogen receptor agonism by isoflavones. Recent in vitro studies suggest that isoflavones, in combination with high estrogen concentrations (within the range seen circulating in premenopausal women), function as estrogen receptor antagonists that potentially may counteract the beneficial effects seen with soy consumption. We studied insulin sensitivity in 15 premenopausal nonhuman primates consuming either a high isoflavone soy diet or a soy-free casein/lactalbumin diet for 4 months. Insulin sensitivity was measured by intravenous glucose tolerance testing, hyperinsulinemic-euglycemic clamps, and insulin-stimulated insulin receptor and protein kinase B phosphorylation levels in muscle. In addition, plasma lipids, adiponectin, thyroid hormone, and body weights are reported. We show that high isoflavones do not adversely affect insulin sensitivity but do significantly alter insulin secretion to glucose stimulation. Small but significant increases in thyroxine and increased high-density lipoprotein cholesterol were observed as has been reported commonly with soy intake. These study results demonstrate that consumption of soy containing high isoflavone levels is not associated with changes in insulin sensitivity in the high estrogen milieu of the premenopausal female.

Investigating potential anti‐diabetic effects of specific soy isoflavones and metabolites in female obese Zucker rats

The purpose of this study was to investigate possible anti‐diabetic effects of the soy isoflavone, daidzein and its metabolite equol in an insulin resistant rodent model. Female obese Zucker rats were randomly assigned to four groups for 11 weeks: casein control (C), injected daidzein (CD), injected equol (CE), and high isoflavone soy protein (H). To bypass GI modification, daidzein and equol were injected and not orally administered. At week 9 animals were subjected to an oral glucose tolerance test (OGTT). At and subsequent to sacrifice, physiological, biochemical, and molecular parameters were examined. Animals on the H diet gained significantly more weight and exhibited a significant increase in food intake when compared to all other groups and also had significantly lower liver weight versus C, CD and CE groups. Additionally, the H animals demonstrated a significantly lower non‐fasted blood glucose level versus the CD and CE groups and the same trend (P&lt;0.07) was observed versus the C group. However, the OGTT did not reveal a significant improvement in glucose tolerance between groups. There was a significant decrease in cholesterol and increase in triglyceride levels in the H group compared to all other groups. Insulin levels were not significantly different between groups. Overall, these results demonstrate differential responses to soy and specific injected soy components and metabolites.

Modulation of methylglyoxal and glutathione by soybean isoflavones in mild streptozotocin-induced diabetic rats

Background and aims Evidence shows that methylglyoxal (MG), a very reactive metabolite of glucose, plays a critical role in the pathogenesis of diabetes and diabetic complications. Although soy isoflavones have beneficial effects in diabetes, the role of soy isoflavones in regulating MG levels is unknown. The present study investigates the effects of soy protein isoflavones on MG and reduced glutathione (GSH). Methods and results Mild diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 35 mg/kg streptozotocin (STZ). The diabetic rats were then randomly divided into three groups and received a special diet supplemented with casein (control), low-isoflavone soy protein (LIS), or high-isoflavone soy protein (HIS) for eight weeks, respectively. Compared to the control or LIS group, HIS diet significantly increased serum insulin levels ( p < 0.01 or 0.05) and reduced serum glucose and MG levels ( p < 0.05). Serum GSH levels were increased in HIS-fed rats compared with the control or LIS group ( p < 0.01). Serum total cholesterol and homocysteine levels were significantly lower in HIS and LIS rats than those of the control rats. Conclusions Both LIS and HIS diets can lower serum lipid and homocysteine levels in this mild diabetic model. HIS diet enhances insulin secretion and reduces glucose level. Moreover, the HIS diet has potential in reducing MG and increasing GSH levels. In addition to its hypoglycemic effect, the antioxidant protection may provide beneficial effects in preventing the development of diabetic complications.

Bone mass and soy isoflavones in socially housed, premenopausal macaques

Background: Soy consumption is associated with a lower incidence of hip fracture in Asian than in Western women, an effect often attributed to estrogen-like compounds (isoflavones) in soy. It is not known whether premenopausal soy exposure initiated in adulthood can increase bone mass and thereby reduce fracture risk.Objective: We aimed to determine whether a high-isoflavone soy diet influences bone mass in soy-naïve, premenopausal cynomolgus monkeys (Macaca fascicularis).Design: Ninety-four skeletally mature females were randomly assigned to consume diets whose protein content came from either high-isoflavone soy or casein and lactalbumin. Animals were socially housed. Bone mass and circulating isoflavone concentrations were measured at baseline and 19 and 31 mo after the start of treatment; bone biomarkers were measured at baseline and 31 mo.Results: There were no significant differences at any timepoint in whole-body bone mineral content between casein-fed (112.5 ± 2.1, 119.2 ± 1.9, and 120.7 ± 2.1 g) and soy-fed (117.2 ± 2.1, 122.4 ± 2.0, and 125.4 ± 2.3 g; P = 0.12) monkeys. Similar results were seen for spinal bone mineral density (casein-fed: 0.46 ± 0.01, 0.50 ± 0.01, and 0.52 ± 0.01 g/cm2; soy-fed: 0.47 ± 0.01, 0.51 ± 0.01, and 0.52 ± 0.01 g/cm2; P = 0.30) and bone biomarker measurements—bone-specific alkaline phosphatase (soy-fed: 82.3 ± 4.1 and 63.2 ± 3.4 ng/mL; casein-fed: 94.1 ± 4.5 and 61.7 ± 4.3 ng/mL; P = 0.22) and C-terminal crosslink of type 1 collagen (soy-fed: 0.944 ± 0.06 and 0.89 ± 0.08 nmol/L; casein-fed: 0.97 ± 0.07 and 0.78 ± 0.06 nmol/L; P = 0.20).Conclusion: A soy diet high in isoflavones does not significantly affect bone characteristics in initially soy-naïve premenopausal monkeys.

Soy Protein and Isoflavones Influence Adiposity and Development of Metabolic Syndrome in the Obese Male ZDF Rat

Background/Aims: Previously, we demonstrated that soy protein ameliorates the diabetic phenotype in several rodent models of obesity and metabolic syndrome (MS). This study was designed to further elucidate factors related to adiposity, glycemic control, and renal function in male Zucker Diabetic Fatty (ZDF/Lepr^fa) rats. Methods: Animals were randomly assigned to one of four diets: control, casein (C); low isoflavone (LIS) soy protein; high isoflavone (HIS) soy protein, or casein + rosiglitazone (CR) for 11 weeks. At sacrifice, physiological, biochemical, and molecular parameters were determined. Results: Body weight and total adiposity were higher in LIS and CR diet groups despite lower food intake. Additionally, these animals exhibited differential regulation of adipose-specific proteins (PPAR-γ and GLUT4) and enzyme activity (FAS and GPDH). HIS-fed animals had reduced total and liver adiposity. Glycemic control was prolonged in both soy-based and rosiglitazone (RGZ) groups. Renal dysfunction was significantly reduced in soy-fed and RGZ-treated rodents as demonstrated by lower levels of proteinuria and dilated tubules with proteinaceous casts. Conclusion: Collectively, these data provide evidence that soy protein with low or high isoflavone content may have therapeutic significance in reducing severity of diabetes, MS, and renal disease as demonstrated in this preclinical model.

Safety and Antioxidant Effects of a Modest Soy Protein Intervention in Hemodialysis Patients

Antioxidant/anti-inflammatory effects of isoflavone-containing soy protein could partly explain why hemodialysis patients in Japan tend to outlive U.S. hemodialysis patients. However, a safety concern is that dialysis patients do not clear isoflavones well. A low-dose intervention with high isoflavone soy protein (25 g protein, four times a week for 4 weeks) was tested in 17 U.S. hemodialysis patients (eight given soy protein, nine given whey protein as a control). Soy protein intake produced no harmful effects based on a typical battery of blood safety tests. Post-treatment isoflavone levels, though high, were similar to those reported after a single 20-g soy protein intake by dialysis patients. In addition, intake of soy, but not whey, reduced plasma values for oxidized low-density lipoprotein, a risk factor for cardiovascular disease, which is a common mortality cause in hemodialysis patients. Three other measures of oxidant stress and/or inflammation were unchanged by the modest high isoflavone soy protein intervention. In conclusion, in hemodialysis patients, a fairly short, low intake level intervention with high isoflavone soy protein produced no obvious harm, and produced one potentially beneficial effect. This justifies tests of higher-dose, longer interventions with soy protein in hemodialysis patients.

Internet based double-blind cross-over clinical trial to test efficacy of high dose isoflavone soy in controlling breast cancer survivor hot flashes

636 Background: Severe hot flashes are common after completion of allopathic breast cancer treatment. Hot flashes are rare in the Orient where high isoflavone soy diets are common. Methods: We enrolled breast cancer survivors experiencing hot flashes after the completion of surgery, radiation and chemotherapy into a 16 week double blind cross-over casein placebo controlled trial of a 160 mg isoflavone soy dietary supplement. Hot flash frequency, severity, and time of day, exercise time and patient journaling was recorded by an internet diary placed on a HIPPA compliant server with password access. Results: Of 168 patients enrolled, 117 actually participated in taking supplementation and completing internet diaries giving adequate data for analysis. Of this group 13 patients dropped out of study for failure to finish all dietary supplements throughout the study period. The hot flash data during the last 4 weeks on each supplement was compared to determine benefit. There was no statistical difference in hot flash frequency, intensity or duration between either supplement independent of exercise level. Interestingly, 82% of patients reported a decrease in hot flashes in the first 4 weeks of study independent of which supplement they were randomized to receive. The journal entries report during this “induction” period that the majority of patients had identified emotional or dietary or other triggers for their hot flashes. The avoidance of the triggers seemed to substantially reduce their reported menopausal symptoms. Conclusions: High dose soy isoflavone dietary supplementation is ineffective in reducing breast cancer survivor hot flashes. Journaling may have a benefit in allowing survivors to find their individual triggers for the most severe hot flashes. Internet patient data entry provides a unique and highly compliant tool for obtaining direct patient reporting in survivorship clinical trials. [Table: see text]

Soy protein intake by active young adult men raises plasma antioxidant capacity without altering plasma testosterone

Soy protein contains antioxidant factors, such as isoflavones, which may help prevent heart disease and cancer. Nonetheless, many active men avoid soy protein because of reports that isoflavones lower testosterone levels. However, soy isoflavone effects on testosterone readings in active young adult males have not been reported. This study found that in such men, a 4-week intake of high-isoflavone soy protein (41.5 g/70 kg body weight per day) had no effect on plasma testosterone values. The soy protein intake did elevate plasma total antioxidant status values (a measure of free radical scavenging). By comparison, intake of whey protein or a placebo (cake mix) had no effect on plasma total antioxidant status readings. Thus, soy protein was found to produce an antioxidant effect in active young adult men without lowering testosterone concentrations.