Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men.

BACKGROUND: Soy isoflavones are potential cancer chemoprevention treatments. OBJECTIVE: We conducted safety studies of purified unconjugated genistein, daidzein, and glycitein, and defined pharmacokinetic parameters for their absorption and metabolism. DESIGN: Thirty healthy men ingested a single dose of 1 of 2 isoflavone preparations purified from soy. The delivered doses of genistein (1, 2, 4, 8, or 16 mg/kg body wt) were higher than those previously administered to humans. Formulation A was composed of 90 +/- 5% genistein, 10% daidzein, and 1% glycitein. Formulation B was composed of 43% genistein, 21% daidzein, and 2% glycitein. RESULTS: We observed no clinically significant behavioral or physical changes after treatment. We observed elevations in lipoprotein lipase and hypophosphatemia that were possibly related to the treatment but that were associated with no clinical toxicity. Considerable quantities of isoflavones were excreted in urine as conjugates. The terminal elimination rate, elimination half-life, area under the curve, maximum plasma concentration, apparent systemic clearance, and volume of distribution were estimated for genistein and daidzein. The mean elimination half-lives with both formulations were 3.2 h for free genistein and 4.2 h for free daidzein. The mean pseudo half-lives were 9.2 h for total genistein and 8.2 h for total daidzein. CONCLUSIONS: Dietary supplements of purified unconjugated isoflavones administered to humans in single doses exceeding normal dietary intake manyfold resulted in minimal clinical toxicity. Genistein and daidzein (free and total) were rapidly cleared from plasma and excreted in urine.     

Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women

BACKGROUND: Soy isoflavones are being evaluated as chemopreventive agents for breast and other cancers. OBJECTIVE: The objective was to perform safety and pharmacokinetic studies of purified unconjugated isoflavone preparations containing genistein, daidzein, and glycitein in postmenopausal women. DESIGN: Twenty-four healthy postmenopausal women ingested a single dose of 1 of 2 purified (from soybeans) isoflavone preparations that delivered a genistein dose of 2, 4, 8, or 16 mg/kg body wt. These doses were higher than those previously administered to human females. Toxicity studies were performed 24 h and 3, 6, 14, and 30 d after isoflavone administration. Kinetic studies were performed during the first 24 h. RESULTS: We observed a 7% decrease in systolic and diastolic blood pressure and a 32% decrease in the neutrophil count 24 h after treatment with formulation A. Isolated episodes of nausea, pedal edema, and breast tenderness were judged to be possibly related to the study treatment. The terminal plasma half-lives for free genistein, daidzein, and glycitein averaged 3.8, 7.7, and 3.4 h, respectively. The terminal pseudo half-lives for total genistein and total daidzein in plasma averaged 10.1 and 10.8 h, respectively. The estimated bioavailabilities of both total genistein and total daidzein from each of the 2 formulations were not significantly different. CONCLUSIONS: A single-dose administration of purified unconjugated isoflavones at amounts that exceed normal dietary intakes had minimal clinical toxicity in healthy postmenopausal women. The pharmacokinetic data suggest that chronic dosing at 12-24-h intervals would not lead to progressive accumulation of these isoflavones.     

Safety of purified isoflavones in men with clinically localized prostate cancer

Our purpose was to evaluate the safety of 80 mg of purified isoflavones administered to men with early stage prostate cancer. A total of 53 men with clinically localized prostate cancer, Gleason score of 6 or below, were supplemented with 80 mg purified isoflavones or placebo for 12 wk administered in 2 divided doses of 40 mg to provide a continuous dose of isoflavones. Compliance, changes in plasma isoflavones, and clinical toxicity were analyzed at baseline, 4, and 12 wk. A total of 50 subjects completed the 12-wk intervention. A continuous, divided-dose administration of 80 mg/day of purified isoflavones at amounts that exceeded normal American dietary intakes significantly increased (P < 0.001) plasma isoflavones in the isoflavone-treated group compared to placebo and produced no clinical toxicity. With the current evidence on the cancer preventive properties of isoflavones, these results are significant and offer promise for these phytochemicals to be developed as potent agents to prevent cancer progression.     

Lycopene and soy isoflavones in the treatment of prostate cancer

Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines. In a previous Phase II clinical trial in prostate cancer patients, we observed prostate-specific antigen (PSA) stabilization with soy isoflavone intake. In this Phase II clinical trial, we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer. To be eligible for the study, men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy. Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33) twice daily orally for a maximum of 6 mo. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill. There was no decline in serum PSA in either group qualifying for a partial or complete response. However, 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer. However, there may not be an additive effect between the 2 compounds when taken together. Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them.     

Lack of significant genotoxicity of purified soy isoflavones (genistein,daidzein, and glycitein) in 20 patients with prostate cancer

BACKGROUND: Genistein may be useful in the prevention or treatment of prostate cancer; however, it causes genetic damage in cultured human cells. OBJECTIVE: The objective was to assess the potential genotoxicity of a purified soy unconjugated isoflavone mixture in men with prostate cancer. DESIGN: Twenty patients with prostate cancer were treated with 300 mg genistein/d for 28 d and then with 600 mg/d for another 56 d. In peripheral lymphocytes, DNA strand breaks were assessed as nuclear tail moment, chromosomal damage was assessed as micronucleus frequency (MF), and translocations of the MLL gene (11q23) were assessed by using fluorescence in situ hybridization. Values are also reported for 6 healthy men. The studies were performed under Investigational New Drug application no. 54 137 at a tertiary referral academic medical center. RESULTS: No changes in group average or individual nuclear tail moment and MF were observed. We observed a single elevated MF value in one subject that exceeded a clinical threshold set before we initiated the study. A significant decrease in average COMET tail moment was observed on day 28 relative to day 0. We detected no genistein-induced rearrangements of the MLL gene in the 3 subjects we studied with this technique. MF increased significantly in lymphocytes exposed in vitro to unconjugated genistein at concentrations > or = 100 micromol/L. Total genistein never exceeded a peak concentration of 27.1 micro mol/L, and unconjugated genistein never exceeded a peak concentration of 0.32 micromol/L. CONCLUSION: Although isoflavones are capable of inducing genetic damage in vitro, a similar effect was not observed in subjects treated with a purified soy unconjugated isoflavone mixture.     

Chemopreventive effects of soy protein and purified soy isoflavones on DMBA-induced mammary tumors in female Sprague-Dawley rats

There are conflicting reports on the effect of soy and its components on mammary carcinogenesis in adult female rats, mainly because of different rodent models that are used in chemoprevention studies. The present study was undertaken to compare the tumor-preventative effects of soy protein isolate (SPI) and two of its isoflavones in a "standard" model that had been used for the identification of many chemopreventive agents. Six groups of female Sprague-Dawley rats were provided with modified cornstarch AIN-76A diets supplemented as follows: no additional agents (control), purified genistein (200 mg/kg diet), purified daidzein (200 mg/kg diet), genistein + daidzein (100 mg/kg diet each), SPI containing normal levels of isoflavones (SPI-n), or SPI depleted of isoflavones (SPI-d). Mammary carcinomas were induced by 7,12-dimethylbenz[a]anthracene (DMBA) introduced 1 wk after the animals began consuming the experimental diets. At the end of the study (120 days after DMBA treatment), no significant differences were found among the six groups with respect to tumor incidence or survival, nor was there a significant reduction in tumor multiplicity in the genistein or genistein + daidzein group. However, there was a 32% reduction in tumor multiplicity in the daidzein and SPI-n groups relative to the control group (P < 0.05). The most effective diet was SPI-d, which produced a 50% reduction in tumor multiplicity relative to the control (P < 0.01). The difference between the SPI-d group and the daidzein or SPI-n group was not significant. Median tumor latency was increased from 53 days in the control group to 68 days in the daidzein group and to 72 days in the SPI-d group, but these differences were not statistically significant. These results show that daidzein and SPI (with normal or low levels of isoflavones) are effective inhibitors of DMBA-induced mammary tumors in adult rats.     

Chemoprevention of rat prostate carcinogenesis by soy isoflavones and by Bowman-Birk inhibitor

Epidemiology studies suggest that soy consumption confers protection against human prostate cancer. To identify the soy component(s) that may be responsible for this chemopreventive activity, studies were conducted to determine the influence of a soy isoflavone mixture (PTI G-2535; 45% genistein, 22% daidzein, 2% glycitein) and a soy-derived protease inhibitor (Bowman-Birk Inhibitor Concentrate; BBIC) on prostate carcinogenesis in rats. Prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate and testosterone propionate, followed by a single intravenous injection of N-methyl-N-nitrosourea (MNU) and chronic androgen stimulation. In separate studies, PTI G-2535 and BBIC were administered continuously at 0 (control), 200, or 2000 mg/kg diet, beginning 1 wk post-MNU. PTI G-2535 and BBIC both conferred modest, but statistically significant and dose-related protection against carcinogenesis in the dorsolateral+anterior prostate. These data demonstrate that both the isoflavone and protein (protease inhibitor) components of soy can inhibit prostate carcinogenesis in the rat. However, the modest individual activities of soy isoflavones and BBIC suggest that while both components may contribute to the chemopreventive activity of soy, combination administration (or exposure to whole soy) may be more effective in prostate cancer prevention than is administration of either component alone.     

A Phase II randomized, placebo-controlled clinical trial of purified isoflavones in modulating steroid hormones in men diagnosed with localized prostate cancer

Our purpose was to evaluate the safety and effectiveness of purified isoflavones in producing an increase in plasma isoflavones and a corresponding change in serum sex hormone binding globulin (SHBG) and steroid hormone levels in men diagnosed with early stage prostate cancer. In this Phase II randomized, double-blinded, placebo-controlled trial, 53 prostate cancer patients with a Gleason score of 6 or below were supplemented with 80 mg purified isoflavones or placebo for 12 weeks. Changes in plasma isoflavones, serum steroid hormones, and safety markers were analyzed from baseline to 12 wk. A total of 50 subjects completed the study. Although significant increases in plasma isoflavones (P < 0.001) was observed with no clinical toxicity, the corresponding modulation of serum SHBG, total estradiol, and testosterone in the isoflavone-treated group compared to men receiving placebo was nonsignificant. Increasing plasma isoflavones failed to produce a corresponding modulation of serum steroid hormone levels in men with localized prostate cancer. The study establishes the need to explore other potential mechanisms by which prolonged and consistent purified isoflavone consumption may modulate prostate cancer risk.     

A combination of tomato and soy products for men with recurring prostate cancer and rising prostate specific antigen

Tomato and soy products are hypothesized to reduce the risk of prostate cancer or enhance efficacy of therapy. A study was completed to determine if men with active prostate cancer will adhere to a dietary intervention rich in tomato products and a soy protein supplement men (n = 41) with recurrent, asymptomatic prostate cancer were randomized among 2 groups: Group A (n = 20) consumed tomato products (no soy) for Weeks 0 through 4, targeting a minimum of 25 mg of lycopene/day. Group B (n = 21) consumed soy (no tomatoes) for Weeks 0 through 4, providing 40 g of soy protein/day. For Weeks 4 through 8, all men consumed a combined tomato-rich diet and soy supplements. No grade II through IV toxicities were observed. During Weeks 0 through 4, mean daily lycopene intake for Group A was 43 mg (+/- 15 mg) and mean soy intake for Group B was 39 g (+/- 1 g), remaining similar during Weeks 4 through 8. Serum lycopene increased from 0.72 +/- 0.09 micromol/l to 1.21 +/- 0.10 micromol/l (P < 0.0001) and urinary isoflavone excretion increased from not detectable to 54.1 +/- 5.7 micromol/l (P < 0.05) with 8 wk of diet intervention. Serum prostate-specific antigen decreased between Weeks 0 and 8 for 14 / 41 men (34%). Mean serum vascular endothelial growth factor for the entire group was reduced from 87 to 51 ng/ml (P < 0.05) over 8 wk. In conclusion, prostate cancer patients will consume diets rich in tomato products and soy with excellent compliance and bioavailability of phytochemicals. Further studies combining tomato and soy foods to determine efficacy for prostate cancer prevention or management are encouraged.     

Goitrogenic and estrogenic activity of soy isoflavones

Soy is known to produce estrogenic isoflavones. Here, we briefly review the evidence for binding of isoflavones to the estrogen receptor, in vivo estrogenicity and developmental toxicity, and estrogen developmental carcinogenesis in rats. Genistein, the major soy isoflavone, also has a frank estrogenic effect in women. We then focus on evidence from animal and human studies suggesting a link between soy consumption and goiter, an activity independent of estrogenicity. Iodine deficiency greatly increases soy antithyroid effects, whereas iodine supplementation is protective. Thus, soy effects on the thyroid involve the critical relationship between iodine status and thyroid function. In rats consuming genistein-fortified diets, genistein was measured in the thyroid at levels that produced dose-dependent and significant inactivation of rat and human thyroid peroxidase (TPO) in vitro. Furthermore, rat TPO activity was dose-dependently reduced by up to 80%. Although these effects are clear and reproducible, other measures of thyroid function in vivo (serum levels of triiodothyronine, thyroxine, and thyroid-stimulating hormone; thyroid weight; and thyroid histopathology) were all normal. Additional factors appear necessary for soy to cause overt thyroid toxicity. These clearly include iodine deficiency but may also include additional soy components, other defects of hormone synthesis, or additional goitrogenic dietary factors. Although safety testing of natural products, including soy products, is not required, the possibility that widely consumed soy products may cause harm in the human population via either or both estrogenic and goitrogenic activities is of concern. Rigorous, high-quality experimental and human research into soy toxicity is the best way to address these concerns. Similar studies in wildlife populations are also appropriate.     

大豆异黄酮的测定方法研究

目的:检测大豆及其制品中黄豆甙、大黄豆甙、染料木甙、黄豆甙元、大黄豆素和金雀异黄素,建立大豆及其制品中6种大豆异黄酮的高效液相色谱-二极管阵列检测器(HPLC-PDA)检测方法。方法:保健食品、豆腐等样品中的大豆异黄酮直接用甲醇水(80+20,v/v)超声提取30 m in,定容过0.45μm滤膜后测定;豆粉和豆奶粉等样品中的大豆异黄酮及其酯类用甲醇水(80+20,v/v)超声提取,提取液经碱性皂化,将某些酯类转化成对应的大豆异黄酮,经盐酸中和,甲醇水(80+20,v/v)定容,过滤膜后测定;酱油和豆豉等样品超声提取30 m in,提取液经OASIS HLB柱去杂质,过0.45μm滤膜,进行液相色谱分析。样品中的6种大豆异黄酮用甲醇和醋酸铵(0.025 mol/L,pH 4.1)作流动相,流速2.0 m l/m in进行梯度洗脱,经250×4.6 mm粒径10μm C18柱分离,二极管阵列检测器(210~400 nm)测定。30 m in内6种大豆异黄酮可得到良好分离。结果:测定6种大豆异黄酮的平均加标回收率在86.7%~116%,加标回收相对标准偏差均小于8%,最底检出限量小于0.04μg。结论:本方法适用于大豆及其制品中大豆异黄酮的测定。     

Decreased growth of human prostate LNCaP tumors in SCID mice fed a low-fat, soy protein diet with isoflavones

Epidemiological studies suggest that high intake of dietary fat is a risk factor for the development of clinical prostate cancer. Soy protein has also been proposed to play a role in the prevention of prostate cancer, and one of the isoflavones in soy protein, genistein, inhibits the growth of human prostate cancer cell lines in vitro. This study was designed to evaluate whether altering dietary fat, soy protein, and isoflavone content affects the growth rate of a human androgen-sensitive prostate cancer cell line (LNCaP) grown in severe-combined immunodeficient (SCID) mice. SCID mice were randomized into four dietary groups: high-fat (42.0 kcal%) + casein, high-fat (42.0 kcal%) + soy protein + isoflavone extract, low-fat (12.0 kcal%) + casein, and low-fat (12.0 kcal%) + soy protein + isoflavone extract. After two weeks on these diets, the mice were injected subcutaneously with 1 x 10(5) LNCaP tumor cells and placed in separate cages (1 mouse/cage) to strictly control caloric intake. Isocaloric diets were given 3 days/wk, and tumor sizes were measured once per week. The tumor growth rates were slightly reduced in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In addition, the final tumor weights were reduced by 15% in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In this xenograft model for prostate cancer, there were statistically significant effects on tumor growth rate and final tumor weight attributable to a low-fat + soy protein + isoflavone extract diet.     

Plasma pharmacokinetics and urinary excretion of isoflavones after ingestion of soy products with different aglycone/glucoside ratios in South Korean women

Asian populations are thought to receive significant health benefits from traditional diets rich in soybeans due to high isoflavone contents. However, available epidemiologic data only weakly support this hypothesis. The present study was carried out to assess the pharmacokinetics of isoflavones in South Korean women after ingestion of soy-based foods. Twenty-six healthy female volunteers (20-30 y old) consumed three different soy products (i.e., isogen, soymilk, and fermented soybeans) with different aglycone/glucoside ratios. Plasma and urine isoflavone concentrations were measured by high-performance liquid chromatography (HPLC) after ingestion of one of the soy products. Pharmacokinetic parameters were determined using the WinNonlin program. The area under the curve (AUC) for plasma daidzein levels of the soymilk group (2,101 ± 352 ng · h/mL) was significantly smaller than those of the isogen (2,628 ± 573 ng · h/mL) and fermented soybean (2,593 ± 465 ng · h/mL) groups. The maximum plasma concentration (C_max) of daidzein for the soymilk group (231 ± 44 ng/mL) was significantly higher than those of the isogen (160 ± 32 ng/mL) and fermented soybean (195 ± 35 ng/mL) groups. The half-lives of daidzein and genistein in the soymilk group (5.9 and 5.6 h, respectively) were significantly shorter than those in the individuals given isogen (9.6 and 8.5 h, respectively) or fermented soybean (9.5 and 8.2 h, respectively). The urinary recovery rates of daidzein and genistein were 42% and 17% for the isogen group, 46% and 23% for the fermented soybean group, and 33% and 22% for the soymilk group. In conclusion, our data indicated that soy products containing high levels of isoflavone aglycone are more effective for maintaining plasma isoflavone concentrations. Additional dose-response, durational, and interventional studies are required to evaluate the ability of soy-based foods to increase the bioavailability of isoflavones that positively affect human health.     

Intake of soy foods and soy isoflavones by rural adult women in China

This study evaluated the intake of soy foods and soy isoflavones by rural adult women and potential determinant factors. Soy food consumption and information on age, education and medical history were collected on 1,188 subjects in Gansu Province and Hebei Province, China using a food frequency questionnaire to gather data on food intake over the past year. Weight and height were simultaneously measured. The results showed that 1139 (95.9%) rural women consumed soy foods in the past year. The average intake of soy foods and isoflavones was 38.7 +/- 58.2 (median = 23.5) g/d and 17.7 +/- 26.6 (median= 8.9) mg/d, respectively. Tofu accounted for the most contribution to their intake. The soy isoflavone intake ranged between 0-35 mg/day in 89.2% of subjects. Gansu women had higher intakes of soy foods and isoflavones than Henbei women (P< 0.05). Women aged 41-50 years consumed less soy foods and isoflavones than the 20-30-year olds and 31-40 year olds(P < 0.05). The intake of soy foods (P< 0.01) and isoflavones (P< 0.01) by women who experienced secondary education or above was significantly higher than illiterate women. Women without a medical history had a higher soy isoflavone intake than women with a medical history, but the difference was not statistically significant. These results suggest that the intake of soy isoflavones by Chinese rural adult women was much higher than women in Western countries. The distribution of intake was skewed to the right and varied among women in regard to region, age group and education level.     

大豆异黄酮对妇女围绝经期症状和性激素的影响

目的了解大豆异黄酮对妇女围绝经期症状的改善作用和对雌激素的影响。方法将已经出现围绝经期症状的45～55岁女性50例,随机单盲分为大豆异黄酮组和安慰剂组,观察8周后的围绝经期症状和雌激素水平。结果大豆异黄酮组试验后BMI增加明显(P0.05);潮热及出汗、Kupperman评分等多项指标有明显改善;雌二醇、促卵泡生成素、睾酮和孕酮有显著性差异(P0.01或P0.05)。与安慰剂组比较,潮热及出汗、性生活状况和Kupperman评分等多项指标差异有显著性(P0.01);除孕酮外其它雌激素指标差异均有显著性(P0.01或P0.05)。安慰剂组试验前后比较虽然检测指标有变化,但无统计学意义。结论大豆异黄酮作为植物雌激素对改善围绝经期症状和提高雌激素水平有广泛的应用前景。     

Health effects of soy protein and isoflavones in humans

Epidemiological investigations suggest that soy consumption may be associated with a lower incidence of certain chronic diseases. Clinical studies also show that ingestion of soy proteins reduces the risk factors for cardiovascular disease. This led to the approval of the food-labeling health claim for soy proteins in the prevention of coronary heart disease by the U.S. FDA in 1999. Similar health petitions for soy proteins have also been approved thereafter in the United Kingdom, Brazil, South Africa, the Philippines, Indonesia, Korea, and Malaysia. However, the purported health benefits are quite variable in different studies. The Nutrition Committee of the American Heart Association has assessed 22 randomized trials conducted since 1999 and found that isolated soy protein with isoflavones (ISF) slightly decreased LDL cholesterol but had no effect on HDL cholesterol, triglycerides, lipoprotein(a), or blood pressure. The other effects of soy consumption were not evident. Although the contributing factors to these discrepancies are not fully understood, the source of soybeans and processing procedures of the protein or ISF are believed to be important because of their effects on the content and intactness of certain bioactive protein subunits. Some studies have documented potential safety concerns on increased consumption of soy products. Impacts of soy products on thyroid and reproductive functions as well as on certain types of carcinogenesis require further study in this context. Overall, existing data are inconsistent or inadequate in supporting most of the suggested health benefits of consuming soy protein or ISF.     

Effects of soy protein isolate consumption on prostate cancer biomarkers in men with HGPIN, ASAP, and low-grade prostate cancer

Fifty-eight men at high risk of prostate cancer or with low-grade prostate cancer were randomly assigned to consume 1 of 3 protein isolates containing 40 g protein: 1) soy protein (SPI+, 107 mg isoflavones/d); 2) alcohol-washed soy protein (SPI-, <6 mg isoflavones/d); or 3) milk protein (MPI). Proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor, B-cell non-Hodgkin lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed in baseline and ending prostate biopsy cores. Serum collected at 0, 3, and 6 mo was analyzed for total and free prostate specific antigen (PSA). Consumption of SPI+ did not alter any of the prostate cancer tumor markers. Bax expression decreased from baseline in the SPI- group, resulting in lower Bax expression than the MPI group. PCNA expression also decreased from baseline in the SPI- group, but this was not different from the other 2 groups. PSA did not differ among the groups at 3 or 6 mo. Interestingly, a lower rate of prostate cancer developed in the soy groups compared to the milk group (P = 0.01). These data suggest that 6-mo SPI+ consumption does not alter prostate tissue biomarkers, SPI- consumption exerts mixed effects, and less prostate cancer is detected after 6 mo of soy consumption regardless of isoflavone content.     

Effect of soy isoflavones on endometriosis: interaction with estrogen receptor 2 gene polymorphism

BACKGROUND: Progression of endometriosis is considered estrogen-dependent. Dietary soy isoflavones may affect the risk of endometriosis, and polymorphisms in estrogen receptor genes may modify this association. We examined associations among soy isoflavone intake, estrogen receptor 2 (ESR2) gene polymorphisms and risk of endometriosis. METHODS: We recruited women age 20-45 years old who had consulted a university hospital for infertility in Tokyo, Japan in 1999 or 2000. A total of 138 eligible women were diagnosed laparoscopically and classified into 3 subgroups: control (no endometriosis), early endometriosis (stage I-II) and advanced endometriosis (stage III-IV). We measured urinary levels of genistein and daidzein as markers for dietary intake of soy isoflavones, and genotyped ESR2 gene RsaI polymorphisms. RESULTS: Higher levels of urinary genistein and daidzein were associated with decreased risk of advanced endometriosis (P for trend = 0.01 and 0.06, respectively) but not early endometriosis. For advanced endometriosis, the adjusted odds ratio for the highest quartile group was 0.21 (95% confidence interval = 0.06-0.76) for genistein and 0.29 (0.08-1.03) for daidzein, when compared with the lowest group. Inverse associations were also noted between urinary isoflavones and the severity of endometriosis (P for trend = 0.01 for genistein and 0.07 for daidzein). For advanced endometriosis, ESR2 gene RsaI polymorphism appeared to modify the effects of genistein (P for interaction = 0.03). CONCLUSIONS: Dietary isoflavones may reduce the risk of endometriosis among Japanese women.     

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.