Mg Of Genistein Research Articles

Genistein effect on cognition in prodromal Alzheimer’s disease patients. The GENIAL clinical trial

BackgroundDelaying the transition from minimal cognitive impairment to Alzheimer’s dementia is a major concern in Alzheimer’s disease (AD) therapeutics.Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimer’s dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms. Our group previously showed that genistein supplementation is effective to treat the double transgenic (APP/PS1) AD animal model.MethodsIn this double-blind, placebo-controlled, bicentric clinical trial, we evaluated the effect of daily oral supplementation with 120 mg of genistein for 12 months on 24 prodromal Alzheimer’s disease patients. The amyloid-beta deposition was analyzed using 18F-flutemetamol uptake. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T), Clock Drawing Test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test.ResultsWe report that genistein treatment results in a significant improvement in two of the tests used (dichotomized direct TAVEC, p = 0.031; dichotomized delayed Centil REY copy p = 0.002 and a tendency to improve in all the rest of them.The amyloid-beta deposition analysis showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p = 0.878), while placebo-treated did increase it (p = 0.036). We did not observe significant changes in other brain areas studied.ConclusionsThis study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer’s dementia in patients with prodromal Alzheimer’s disease. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study.Trial registrationNCT01982578, registered on November 13, 2013.

A novel method for highly efficient biotransformation and separation of isoflavone aglycones from soybean with high-speed counter-current chromatography

A novel bioreactor with high-speed counter-current chromatography (HSCCC) was established for the efficient biotransformation of isoflavone aglycones from soybeans. Further, the transformed isoflavone aglycones were separated by HSCCC with continuous injection mode. β-Glucosidase and snailase were chosen as the optimum enzymes for HSCCC bioreactor biotransformation. Compared with snailase, β-glucosidase showed the advantages in both enzymatic hydrolysis efficiency and the influence to retention of the stationary phase and 4 mL/min were selected as the optimum elution flow-rate. The transformed isoflavone aglycones were separated by HSCCC with a solvent system n-hexane/ethyl acetate/ethanol/water (1:1.6:1:1.6, v/v). From 200 mg crude samples, 82 mg of daidzein, 48 mg of glycitein and 24 mg of genistein were separated with purities over 95%, respectively, as determined by HPLC. The chemical structures of these compounds were identified by EI-MS and 1H-NMR. Our results suggest that HSCCC could be developed as a bioreactor in the preparation of isoflavone aglycones from soybeans for the facility to immobilize and recycle the enzyme.

Effect of dietary supplementation of phytochemicals on immunity and haematology of growing broiler chickens

The current study investigated the effects of phytochemicals genistein and/or hesperidin dietary supplementation on immunity and haematology of growing broilers. A total of 360 1-day-old broiler chicks (Arbor Acres, mixed sex) were randomly assigned to six treatment groups, namely T0, control; T1 and T2, supplemented with 5 and 20 mg of genistein and hesperidin; while T3, T4, and T5 diets contained 5, 10, and 20 mg of genistein + hesperidin (1:4) mixture, respectively, per kg of diet. The white blood cell count was significantly (p < .01) increased in T1, T2, T4, and T5 compared with the control (T0) group. The haemoglobin concentration significantly (p < .01) increased in the T5 group, while mean corpuscular haemoglobin concentration was significantly (p < .05) higher in T4 compared with the T0 group. Antibody titres against Newcastle disease significantly (p < .01) increased in T1, T2, T3, T4, and T5 compared with the T0 group. Similarly, all phytochemicals treated groups exhibited an increase (p < .01) in antibody titres against Avian Influenza virus, as compared with the controls. At the same time, the supplemented groups had significantly (p < .01) higher neutrophil adhesion rate and cutaneous basophil hypersensitivity test representing the cellular immune response than the controls. In conclusion, supplementation with both phytochemicals, genistein and hesperidin, positively influenced the immune parameters and haematological profile of growing broilers, thus might be considered as feed additives in broiler industry.

Exogenous genistein in late gestation: effects on fetal development and sow and piglet performance

Due to their functional similarity to estradiol, phytoestrogens could prove to be beneficial in late gestating sows. The goal of this study was to determine the impact of providing the phytoestrogen genistein during late pregnancy on the performance of sows and their litters. In total, 56 gilts were equally divided into the two following groups on day 90 of gestation: (1) controls (CTL); and (2) two daily i.m. injections of 220 mg of genistein (GEN). Treatments were carried out until farrowing. Jugular blood samples were collected from 16 gilts/treatment on days 89 and 110 of gestation, and on days 3 and 21 of lactation. Milk samples were also obtained from those sows on day 3 of lactation. A male piglet from 16 CTL and 15 GEN litters was slaughtered at 24 h postpartum and a blood sample was obtained. The liver, heart and visceral organs were weighed and the semitendinosus (ST) muscle was collected and carcass composition was determined. The treatment increased (P<0.05) the concentrations of genistein and daidzein in the plasma of gilts on day 110 of gestation and of genistein in the plasma of piglets at 24 h postpartum. It also increased IGF1 concentrations in gilts at the end of the treatment period (P<0.05). Genistein had no impact (P>0.1) on weight or backfat loss of sows during lactation, milk composition or weights of piglets. The pre-weaning mortality rate of piglets was very low (<7%), yet the odds ratio comparing CTL with GEN sows indicated almost twice as many chances of pre-weaning deaths occurring in litters from CTL than GEN sows. Weights of the piglet carcasses were similar for both treatments, as well as weights of the various organs and of the ST muscle (P>0.1). However, carcasses from GEN litters contained more fat than those from CTL litters (9.63% v. 8.34%, P<0.05). None of the biochemical properties of the ST muscle differed between groups (P>0.1). In conclusion, injecting gilts with 440 mg/day of genistein in late gestation increased IGF1 concentrations in gilts and carcass fat in neonatal piglets, but had minimal effect on muscle development of piglets at birth and on the performance of lactating sows and their litters.

Preparative isolation and purification of seven compounds from Hibiscus mutabilis L. leaves by two-step high-speed counter-current chromatography

Seven compounds from Hibiscus mutabilis L. leaves were first successfully achieved by two-step high-speed counter-current chromatography with two-phase solvent system composed of n-butanol-ethyl acetate-water (1:6:9, v/v/v) and n-hexane-ethyl acetate-methanol-water (3:5:3:5, v/v/v/v/). The critical experimental parameters of first-step separation were optimized with response surface methodology as follows: flow rate was 1.1 mL/min, revolution speed was 800 rpm and temperature was 30?C. Under the optimal conditions, around 5.0 mg of salicylic acid, 13.6 mg of rutin, 5.5 mg of genistein were obtained in 100 mg crude sample. Then, 9.2 mg of potengriffioside A, 4.7 mg of kaempferol 3-O-rutinoside, 3.0 mg of steppogenin and 2.5 mg of emodin were obtained by second-step separation. The purities of the seven compounds determined by UPLC were 96.2%, 93.8%, 95.4%, 94.3%, 98.0%, 94.1% and 90.8%, respectively. Their chemical structures were identified by electron spray ionization mass spectroscopy (ESI-MS) and 1H, 13C nuclear magnetic resonance (NMR). Furthermore, compound steppogenin and genistein were first reported from Hibiscus mutabilis L. The purification method was simple, efficient and evaded tedious separation process.

Effects of Short Term Administration of Genistein on Hypothalamic and Anterior Pituitary Hormones in Ovariectomized Gilts

Administration of genistein to barrows increased anterior pituitary (AP) concentrations of IGF-I and LH and increased expression of AP IGF receptor. Whether similar changes occur in gilts remains to be determined. The objective of this experiment was to determine if short term administration of genistein increased expression of components of the AP IGF system and hypothalamic hormones and receptors involved in gonadotropin synthesis and/or release in the gilt. Sixteen crossbred gilts of similar weight (97.7 kg) were ovariectomized and assigned to either control (C; n = 8) or genistein (G; n = 8) groups. Genistein pigs received 800 mg of genistein in DMSO while C pigs received an equal volume of DMSO i.m. on day 0, 1, 2, and 3. Blood samples were obtained on day 0, 1, 2, and 3. Pigs were slaughtered on d 4 when blood, AP, and medial basal hypothalami (MBH) were collected. No difference was detected (P > 0.05) in AP concentrations of IGF-I or serum concentrations of IGF-I in C and G pigs. Anterior pituitary concentrations of LH were greater (P 0.05) in C and G pigs. Relative expression of AP IGFBP-5 and GnRHR was increased (P < 0.05) in G pigs compared with C pigs. Relative expression of AP LHβ did not differ between C and G pigs. Relative expression of MBH kisspeptin was greater (P < 0.01) in G pigs than C pigs. These data provided evidence that short term administration of genistein increased expression of hypothalamic and hypophyseal hormones in gilts which could influence subsequent reproduction.

Daidzein and genistein fail to improve glycemic control and insulin sensitivity in Chinese women with impaired glucose regulation: A double-blind, randomized, placebo-controlled trial.

This randomized, double-blind, and placebo-controlled trial evaluated the effect of isolated daidzein and genistein on glycemic control and insulin sensitivity in 165 Chinese women aged 30-70 with impaired glucose regulation (IGR). Participants were randomly assigned to one of three groups with a daily dose of 10 g of soy protein plus (i) no addition, (ii) 50 mg of daidzein, or (iii) 50 mg of genistein for 24 wk. Fasting glucose (FG), insulin, and glycosylated hemoglobin (HbA1c ), and glucose concentrations at 30, 60, 120, and 180 min and insulin concentrations at 30, 60, and 120 min after an oral 75-g glucose tolerance test were assessed at baseline and at 12 and 24 wk postintervention. a total of 158 and 151 subjects completed the measures at wk 12 and 24, respectively. There were no significant differences in the changes (%) of FG and the 2-h glucose, HbA1c , fasting, and 2-h insulin or the area under the curve of glucose and insulin between the three treatment groups at wk 12 or 24 (all p > 0.05). Neither isolated daidzein nor genistein has a significant effect on glycemic control and insulin sensitivity in Chinese women with IGR over a 6-month supplementation period.

Effects of genistein and hesperidin on biomarkers of heat stress in broilers under persistent summer stress

This study investigated the supplemental effects of the flavonoids genistein and hesperidin for biomarkers of heat stress in broilers reared under persistent summer stress. A total of 360 one-day-old, mixed-sex broiler chickens were divided into 6 treatment groups: control or supplemented with 5 mg of genistein·kg of feed−1, 20 mg of hesperidin·kg of feed−1, or a mixture of genistein and hesperidin (1:4) at a dosage of 5 mg·kg−1, 10 mg·kg−1, and 20 mg·kg−1 of feed. Broilers were slaughtered at 42 d and samples were analyzed for hematological profile, creatine kinase, lactate dehydrogenase, and heat shock protein 70 mRNA levels. Results showed that dietary genistein and hesperidin improved (P < 0.05) the weekly performance of broilers particularly during the finisher period. The circulating heterophils and heterophil-to-lymphocyte ratios were found to decrease (P < 0.01) in the treated groups. Moreover, biomarkers of heat stress including the level of creatine kinase, lactate dehydrogenase, and heat shock protein 70 mRNA of breast muscle was also changed (P < 0.01) positively by the dietary compounds with pronounced effects of combined treatments. These findings suggested that genistein and hesperidin could be a prime strategy to ameliorate summer stress effects in broilers; and a combination of both compounds may lead to mutual synergistic effects. It could be suggested that dietary use of both genistein and hesperidin as a feed supplement may offer a potential nutritional strategy in tropical and subtropical regions to overcome the deleterious effects of persistent summer stress in broiler production.

Effect of increasing levels of bioflavonoids in broiler feed on plasma anti-oxidative potential, lipid metabolites, and fatty acid composition of meat

This study was conducted to investigate the supplemental effects of purified bioflavonoids (genistein and hesperidin), as potential alternatives to plant/herbs or synthetic antioxidants, individually and in combination for fatty acid profile, lipid metabolites, and antioxidant status of broilers. Three hundred sixty 1-d-old broilers were divided into 6 treatment groups: control (basal diet), G5 (5 mg of genistein per kg of feed), and H20 (20 mg hesperidin per kg of feed), whereas the other 3 groups were supplemented with a mixture of genistein and hesperidin (20% genistein + 80% hesperidin) having a dosage of 5 mg•kg(-1) (GH5), 10 mg•kg(-1) (GH10), and 20 mg•kg(-1) (GH20), respectively. Broilers were slaughtered at 42 d, and breast muscle, liver, and blood samples were collected. A dose-dependent increase (P < 0.05) was observed for plasma antioxidant parameters, including total antioxidant capacity, malondialdehyde production, and total superoxide dismutase activity. Cholesterol and triglyceride contents were found to decrease (P < 0.05) in serum and breast muscle. The proportion of total polyunsaturated fatty acids and the ratio of n-6 to n-3 fatty acids and polyunsaturated fatty acids to saturated fatty acids in breast muscles was significantly improved (P < 0.05) by increasing levels of dietary bioflavonoids. The current results implied that dietary bioflavonoids genistein and hesperidin could positively improve the fatty acid and lipid metabolite profile of broiler breast meat in a dose-dependent fashion. Thus, bioflavonoids could be a feasible alternative of antioxidant plants/herbs and synthetic feed additives for the production of healthier chicken meat.

Effects of dose and route of administration of genistein on isoflavone concentrations in post-weaned and gestating sows

Phytoestrogens could be a useful tool in swine husbandry practices because of their structural and functional similarities to estradiol. The goal of this study was to compare various routes and doses of administration of the phytoestrogen genistein in sows of two different physiological statuses. Circulating concentrations of isoflavones, estradiol and IGF-I were determined. In experiment 1, 65 sows were equally divided into the five following groups, between days 3 and 5 of the first or second estrous cycle post weaning: (1) controls (CTL); (2) 1 g of genistein fed daily (OR1); (3) 2 g of genistein fed daily (OR2); (4) two daily i.m. injections of 200 mg of genistein (IM400); and (5) two daily i.m. injections of 400 mg of genistein (IM800). Treatments were carried out for 10 days. In experiment 2, 10 sows were equally divided into two groups on day 90 of gestation, namely, controls (CTL) or 2 g of genistein fed daily for 10 days (OR2). In both trials, jugular blood samples were collected on days 1 (before treatment), 5 and 10 at 0730 h. In experiment 1, a blood sample was also collected at 1730 h on day 10 for CTL, IM400 and IM800 sows. In experiment 1, circulating concentrations of genistein on days 5 and 10 were greater in OR2, IM400 and IM800 than in CTL and OR1 group sows (P < 0.01). Daily dietary supplementation with 2 g of genistein resulted in blood concentrations that were similar to those in animals given daily two i.m. injections of 200 mg. Values of all isoflavones, except equol, which was not detectable, were greater in PM than in AM on day 10 (P < 0.01). In experiment 2, genistein concentrations were greater in OR2 compared with CTL on days 5 and 10 (P ⩽ 0.05). There was no difference in the genistein response to OR2 because of physiological status (i.e. weaned v. gestating, P > 0.1). Estradiol and IGF-I concentrations were not altered by any of the treatments (P > 0.1). Providing genistein either per os or via i.m. injections increased circulating concentrations of genistein in female swine within 5 days of the onset of treatment. The genistein response to i.m. injections of genistein was similar in weaned and late-pregnant sows, even though endogenous concentrations of estradiol differed. This response was specific in that estradiol, IGF-I and isoflavones other than genistein were not affected by treatments.

Dietary Supplementation with Genistein Increases Hepcidin Expression in Wild Type Mice

Abstract 3208Iron overload is an important cause of morbidity and death in patients with hemoglobinopathies, transfusion-dependent anemias, and hereditary hemochromatosis. As humans have no means of excreting iron, regulation of iron homeostasis depends on limiting intestinal iron absorption and optimizing iron release from macrophages to developing erythrocytes. Hepcidin, a peptide hormone produced in the liver, modulates intestinal iron absorption and macrophage iron release via effects on ferroportin. Hepcidin is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. We conducted a small-scale chemical screen and found that the isoflavone genistein, a major dietary component of soybeans, enhanced Hepcidin transcript levels in zebrafish embryos. Furthermore genistein treatment increased Hepcidin transcript levels and Hepcidin promoter activity in human hepatocytes (HepG2 cells) in a Stat3 and Smad4-dependent manner. To evaluate genistein's effect in a mammalian model, we placed groups of 4 four-week old male C57BL/6 mice on an iron-sufficient, low soy diet (AIN93G containing 35 mg of iron/kg) supplemented with 0, 250, or 500 mg of genistein per kg of food for 7 weeks, and then sacrificed the animals for analysis. Plasma genistein levels (mean±SE) at the time of sacrifice were 0.015±0.015, 0.52±0.173, and 2.07±0.65 micromolar, respectively. Compared to mice not treated with genistein, the 250 mg/kg dose produced a significant increase in hepatic Hepcidin (HAMP1) transcript levels (1.49±0.10 vs 0.93±0.10, p=0.01), while the 500 mg/kg dose did not. Although liver iron content, spleen iron content, and weight gain were not significantly different among the groups, the ratio of Hepcidin expression to liver iron content was significantly increased in the animals treated with genistein 250 mg/kg compared to controls (0.013±0.0009 vs 0.0074±0.00068, p=0.0068). In conclusion, genistein is the first orally administered small molecule experimental drug shown to increase Hepcidin transcript levels in vivo. Future experiments will evaluate the effects of genistein on genetic models of iron overload syndromes. Disclosures:No relevant conflicts of interest to declare.

Acute genistein treatment mimics the effects of estradiol by enhancing place learning and impairing response learning in young adult female rats

Endogenous estrogens have bidirectional effects on learning and memory, enhancing or impairing cognition depending on many variables, including the task and the memory systems that are engaged. Moderate increases in estradiol enhance hippocampus-sensitive place learning, yet impair response learning that taps dorsal striatal function. This memory modulation likely occurs via activation of estrogen receptors, resulting in altered neural function. Supplements containing estrogenic compounds from plants are widely consumed despite limited information about their effects on brain function, including learning and memory. Phytoestrogens can enter the brain and signal through estrogen receptors to affect cognition. Enhancements in spatial memory and impairments in executive function have been found following treatment with soy phytoestrogens, but no tests of actions on striatum-sensitive tasks have been made to date. The present study compared the effects of acute exposure to the isoflavone genistein with the effects of estradiol on performance in place and response learning tasks. Long–Evans rats were ovariectomized, treated with 17β-estradiol benzoate, genistein-containing sucrose pellets, or vehicle (oil or plain sucrose pellets) for 2days prior to behavioral training. Compared to vehicle controls, estradiol treatment enhanced place learning at a low (4.5μg/kg) but not high dose (45μg/kg), indicating an inverted pattern of spatial memory facilitation. Treatment with 4.4mg of genistein over 2days also significantly enhanced place learning over vehicle controls. For the response task, treatment with estradiol impaired learning at both low and high doses; likewise, genistein treatment impaired response learning compared to rats receiving vehicle. Overall, genistein was found to mimic estradiol-induced shifts in place and response learning, facilitating hippocampus-sensitive learning and slowing striatum-sensitive learning. These results suggest signaling through estrogen receptor β and membrane-associated estrogen receptors in learning enhancements and impairments given the preferential binding of genistein to the ERβ subtype and affinity for GPER.

Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity

This analysis was conducted to determine the efficacy of extracted or synthesized soybean isoflavones in the alleviation of hot flashes in perimenopausal and postmenopausal women. PubMed and The Cochrane Controlled Clinical Trials Register Database were searched for relevant articles reporting double-blinded randomized controlled trials through December 14, 2010. References within identified articles, as well as peer-reviewed articles that had come to the attention of the authors through other means, were also examined for suitability. This systematic review and meta-analysis, which evaluated the effects of isoflavones on the frequency, severity, or composite score (frequency × severity) of hot flashes compared with placebo was conducted according to Cochrane Handbook guidelines. From 277 potentially relevant publications, 19 trials (reported in 20 articles) were included in the systematic review (13 included hot flash frequency; 10, severity; and 3, composite scores), and 17 trials were selected for meta-analyses to clarify the effect of soybean isoflavones on hot flash frequency (13 trials) and severity (9 trials). Meta-analysis revealed that ingestion of soy isoflavones (median, 54 mg; aglycone equivalents) for 6 weeks to 12 months significantly reduced the frequency (combined fixed-effect and random effects model) of hot flashes by 20.6% (95% CI, -28.38 to -12.86; P < 0.00001) compared with placebo (heterogeneity P = 0.0003, I = 67%; random effects model). Meta-analysis also revealed that isoflavones significantly reduced hot flash severity by 26.2% (95% CI: -42.23 to -10.15, P = 0.001) compared with placebo (heterogeneity, P < 0.00001, I = 86%; random effects model). Isoflavone supplements providing more than 18.8 mg of genistein (the median for all studies) were more than twice as potent at reducing hot flash frequency than lower genistein supplements. Soy isoflavone supplements, derived by extraction or chemical synthesis, are significantly more effective than placebo in reducing the frequency and severity of hot flashes. Additional studies are needed to further address the complex array of factors that may affect efficacy, such as dose, isoflavone form, baseline hot flash frequency, and treatment duration.

Long-term soy isoflavone supplementation and cognition in women

To determine the cognitive effects of long-term dietary soy isoflavones in a daily dose comparable to that of traditional Asian diets. In the double-blind Women's Isoflavone Soy Health trial, healthy postmenopausal women were randomly allocated to receive daily 25 g of isoflavone-rich soy protein (91 mg of aglycone weight of isoflavones: 52 mg of genistein, 36 mg of daidzein, and 3 mg glycitein) or milk protein-matched placebo. The primary cognitive endpoint compared between groups at 2.5 years was change from baseline on global cognition, a composite of the weighted sum of 14 neuropsychological test score changes. Secondary outcomes compared changes in cognitive factors and individual tests. A total of 350 healthy postmenopausal women aged 45-92 years enrolled in this trial; 313 women with baseline and endpoint cognitive test data were included in intention-to-treat analyses. Adherence in both groups was nearly 90%. There was no significant between-group difference on change from baseline in global cognition (mean standardized improvement of 0.42 in the isoflavone group and 0.31 in the placebo group; mean standardized difference 0.11, 95% confidence interval [CI] -0.13 to 0.35). Secondary analyses indicated greater improvement on a visual memory factor in the isoflavone group (mean standardized difference 0.33, 95% CI 0.06-0.60) but no significant between-group differences on 3 other cognitive factors or individual test scores, and no significant difference within a subgroup of younger postmenopausal women. For healthy postmenopausal women, long-term dietary soy isoflavone supplementation in a dose comparable to that of traditional Asian diets has no effect on global cognition but may improve visual memory. This study provides Class I evidence that long-term dietary supplementation with isoflavone-rich soy protein does not improve global cognition of healthy postmenopausal women.

Effects of the phytoestrogen genistein on the porcine anterior pituitary insulin-like growth factor system

Estrogens have profound effects on the serum and anterior pituitary (AP) insulin-like growth factor (IGF) system in pigs. In this study we determined whether administration of the phytoestrogen genistein increased serum and AP concentrations of IGF-I and relative amounts of serum and AP insulin-like growth factor-binding protein (IGFBP). Twenty barrows of similar age (190 d) and weight (110 kg) were stratified by litter into one of four treatments: controls (C), estradiol (E), 200 mg genistein (G200), and 400 mg genistein (G400). Estradiol-treated pigs were injected daily with 2 mg of estradiol-17β intramuscularly (i.m.), whereas the G200 and G400 groups were injected daily with either 200 or 400 mg of genistein i.m., respectively, beginning on d 0 and continuing through d 15. Blood was collected on d 0, 3, 6, 9, and 13. Blood and AP were collected at slaughter on d 16. Serum and AP concentrations of IGF-I and luteinizing hormone (LH) were determined by radioimmunoassay. Relative amounts of serum IGFBP were determined by Western ligand blot analysis. Relative expression of AP IGF-I, IGF-I receptor (IGF-IR), gonadotropin-releasing hormone receptor, and LHβ subunit was determined by real-time reverse transcriptase polymerase chain reaction. Anterior pituitary concentrations of IGF-I were greater (P > 0.05) in E and G400 pigs compared with controls, whereas AP concentrations of LH were greater (P < 0.05) in G400 pigs compared with C and G200 pigs. Relative expression of LHβ was greater in G200 pigs compared with C pigs but did not differ from that in G400 pigs. Relative expression of AP IGF-IR was greater (P < 0.05) in E pigs compared with all other treatments; however, relative expression of AP IGF-IR was greater (P < 0.05) in both G200 and G400 pigs vs C pigs. No differences were detected (P > 0.05) in serum concentrations of IGF-I or relative amounts of serum and AP IGFBP among treatments. These data provide evidence that genistein is capable of modulating components of the AP IGF system that could affect the synthesis and release of LH.

Soy Isoflavones Ameliorate the Adverse Effects of Chemotherapy in Children

Genistein sensitizes cancer cells to chemotherapy and radiation by modulating cell survival pathways. At the same time, genistein's antioxidant and anti-inflammatory effects may protect normal tissues from adverse effects of chemotherapy and radiation, which are largely due to oxygen-free radicals and inflammation. We conducted a small pilot study with a soy isoflavone mixture containing 8 mg of genistein in children receiving chemotherapy and/or radiation to investigate genistein's potential toxicity preventive effect. We monitored clinical and laboratory parameters in children with cancer who received their first cycle of chemotherapy without genistein and the subsequent cycles with genistein. Patients served as their own controls, and the clinical-laboratory data from the first cycle were compared to the data from subsequent cycles. Nine cycles of chemotherapy were administered without genistein and 57 cycles with genistein. Patients experienced less myelosuppression, mucositis, and infection when they received genistein with chemotherapy. During supplementation, serum genistein levels were 2 to 6 times higher compared to presupplementation levels. Patients who received abdominal radiation reported less pain and diarrhea when they took the genistein supplement. Further clinical investigation of soy isoflavones in pediatric cancer patients receiving chemotherapy and/or radiation should be conducted.

Soy isoflavones, diet and physical exercise modify serum cytokines in healthy obese postmenopausal women

Evaluate the effect of diet, physical exercise, and a daily oral intake of a soy isoflavones extract (Fisiogen(®)) contained 200 mg of Glycine max, which corresponded to 80 mg of isoflavone (60.8 mg of genistein, 16 mg of daidzein and 3.2 mg of glicitein) on leptin and other adipokines plasma levels in healthy obese postmenopausal women. A multicentric randomized longitudinal prospective cohort study was conducted in a sample of 87 healthy obese postmenopausal women. Patients were randomly assigned to a 1200 kcal diet and exercise group (control group) or a group of 1200 kcal diet, exercise, and daily oral intake of daily oral intake of a soy isoflavones extract (Fisiogen(®)) contained 200 mg of Glycine max, which corresponded to 80 mg of isoflavone (60.8 mg of genistein, 16 mg of daidzein and 3.2 mg of glicitein) (soy isoflavones group) along 6 months. Main outcome measures were: anthropometric measures, body composition, leptin, adiponectin, TNF-alpha, homocysteine, C-reactive protein, glucose, insulin, lipid profile and oestradiol serum levels, Kupperman index and Cervantes Scale. Mean serum leptin and TNF-alpha levels declined after 6 months in both groups of the study, but only women in the soy isoflavones group showed a significant increase of mean serum levels of adiponectin. Diet, physical exercise and daily oral intake of a soy isoflavones extract (Fisiogen(®)) contained 200 mg of Glycine max, which corresponded to 80 mg of isoflavone (60.8 mg of genistein, 16 mg of daidzein and 3.2 mg of glicitein) have a beneficial effect on serum leptin, adiponectin and TNF-α in healthy obese postmenopausal women after 6 months of treatment.

Soy extract phytoestrogens with high dose of isoflavones for menopausal symptoms

The aim of the present study was to assess the efficacy and safety of a standardized compound based on an extract of soy phytoestrogens, with high doses of isoflavones in the management of menopausal hot flushes. A total of 180 women aged 40-65 years with a minimum of five moderate-to-severe hot flushes in the last 7 days at baseline and absence of menstruation for at least 6 months participated in a 12-week prospective, randomized, double-blind, placebo-controlled multicenter trial. After a 2-week run-in period, women received one tablet a day of 80 mg isoflavones (corresponding to 60 mg of genistein) or a matching placebo. The mean daily number of moderate-to-severe hot flushes decreased in both study groups, but the reduction was greater in the isoflavones arm at 6 (36.2%) and 12 weeks (41.2%) than in the placebo arm (24.0% at 6 weeks, 29.3% at 12 weeks), with a difference of 1.1 (95% CI [-2.0 to -0.06]) (P = 0.038) at 6 weeks and 1.1 (95% CI [-2.05 to -0.15]) (P = 0.023) at 12 weeks. Similar findings were obtained for hot flushes of any intensity. The Kupperman index decreased in both study groups. Relief of hot flushes was greater when time to menopause was >or=12 months and in cases of BMI >or=27 kg/m(2). In daily practice conditions, high doses of isoflavones, particularly genistein, can be used for the management of hot flushes in postmenopausal women not treated with hormone replacement therapy due to their superior efficacy to placebo and very good safety profile.

Soy isoflavones and fatty acids: Effects on bone tissue postovariectomy in mice

Osteoporosis is a silent disease that leads to fragility fractures that can diminish quality of life and contribute to death. With no ideal drug treatment available to manage osteoporosis, soy isoflavones (ISO), and omega-3 long chain PUFAs in fish oil (FO) may be integral in a dietary strategy that prevents bone loss. The overall objective of this study was to determine if combining ISO with omega-3 long chain PUFAs resulted in greater protection against the loss of bone mineral and skeletal weakening in ovariectomized mice. Ovariectomized CD-1 mice were randomized to control diet or a diet containing ISO alone (250 mg of genistein + 250 mg of daidzein/kg diet), FO alone (7% menhaden oil), or ISO + FO. Each dietary intervention prevented the loss of bone mineral density (BMD) in the femur and preserved femur strength, but only FO, either alone or combined with ISO, resulted in a higher BMD of lumbar vertebra (LV). Most notably, FO + ISO resulted in a higher peak load of LV4, indicating that vertebra were more resistant to fracture. Whether a dietary strategy providing FO in combination with ISO attenuates bone loss in postmenopausal women awaits investigation.

Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women

Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive. To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women. Randomized, double-blind, placebo-controlled trial. 3 university medical centers in Italy. 389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions. After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n = 191) or 54 mg of genistein (n = 198) daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D. The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected. At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine (change, 0.049 g/cm2 [95% CI, 0.035 to 0.059] vs. -0.053 g/cm2 [CI, -0.058 to -0.035]; difference, 0.10 g/cm2 [CI, 0.08 to 0.12]; P < 0.001) and the femoral neck (change, 0.035 g/cm2 [CI, 0.025 to 0.042] vs. -0.037 g/cm2 [CI, -0.044 to -0.027]; difference, 0.062 g/cm2 [CI, 0.049 to 0.073]; P < 0.001). Genistein statistically significantly decreased urinary excretion of pyridinoline and deoxypyridinoline, increased levels of bone-specific alkaline phosphatase and insulin-like growth factor I, and did not change endometrial thickness compared with placebo. More genistein recipients than placebo recipients experienced gastrointestinal side effects (19% vs. 8%; P = 0.002) and discontinued the study. The study did not measure fractures and had limited power to evaluate adverse effects. Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. ClinicalTrials.gov registration number: NCT00355953.