Soy proteins and isoflavones reduce interleukin-6 but not serum lipids in older women: a randomized controlled trial

Soy foods contain several components, notably, isoflavones and amino acids, that may improve cardiovascular health. We evaluated the long-term effect of soy protein and/or soy isoflavones supplementation on serum lipids and inflammatory markers using a 1-year randomized, double-blind, placebo-control, clinical trial in 131 healthy ambulatory women older than 60 years. We hypothesized that soy protein, in combination with isoflavones, would have the largest positive effect on coronary heart disease risk factors (serum lipids and inflammatory markers) compared with either intervention alone and that, within groups receiving isoflavones, equol producers would have more positive effects on coronary heart disease risk factors than nonequol producers. After a 1-month baseline period, participants were randomized into 1 of 4 intervention groups: soy protein (18 g/d) and isoflavone tablets (105 mg/d isoflavone aglycone equivalents), soy protein and placebo tablets, control protein and isoflavone tablets, or control protein and placebo tablets. T Tests were used to assess differences between equol and nonequol producers. Ninety-seven women completed the trial. Consumption of protein powder and isoflavone tablets did not differ among groups, and compliance with study powder and tablets was 79% and 90%, respectively. After 1 year, in the entire population, there were either no or little effects on serum lipids and inflammatory markers, regardless of treatment group. Equol producers, when analyzed separately, had significant improvements in total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios (−5.9%, P = .02; −7.2%, P = .04 respectively). Soy protein and isoflavone (either alone or together) did not impact serum lipids or inflammatory markers. Therefore, they should not be considered an effective intervention to prevent cardiovascular disease because of lipid modification in healthy late postmenopausal women lacking the ability to produce equol.     

Probiotic consumption does not enhance the cholesterol-lowering effect of soy in postmenopausal women

Numerous studies report that soy lowers cholesterol. Probiotic bacteria were also reported to lower total cholesterol (TC) and LDL cholesterol (LDL-C). We hypothesized that by altering intestinal microflora, probiotic consumption may also change phytoestrogen metabolism and enhance the effects of soy. To evaluate the independent and interactive effects of probiotic bacteria and soy on plasma TC, LDL-C, HDL cholesterol (HDL-C), and triglycerides (TG), 37 women with a baseline TC of 5.24 mmol/L were given the following 4 treatments for 6 wk each in a randomized crossover design: soy protein isolate (26 +/- 5 g soy protein containing 44 +/- 8 mg isoflavones/d); soy protein isolate + probiotic capsules (10(9) colony-forming units Lactobacillus acidophilus DDS-1 and Bifidobacterium longum); milk protein isolate (26 +/- 5 g milk protein/d); and milk protein isolate + probiotic. Soy consumption decreased plasma TC by 2.2% (P = 0.02) and LDL-C by 3.5% (P = 0.005), increased HDL-C by 4.2% (P = 0.006) and tended to decrease TG (P = 0.07) compared with milk protein intake. When divided according to initial TC concentration, soy effects were observed only in hypercholesterolemic women (TC > 5.17 mmol/L). In this subgroup, soy treatments decreased plasma TC by 3.3% (P = 0.01), LDL-C by 4.5% (P = 0.004), and TG by 10.6% (P = 0.02), and increased HDL-C by 4.2% (P = 0.02). When subjects were divided on the basis of plasma and urine concentrations of the isoflavone metabolite, equol, equol producers and nonproducers did not differ in baseline lipids or in the effects of soy. Probiotics did not lower cholesterol or enhance the effects of soy. These results confirm a beneficial effect of soy on plasma cholesterol in mildly hypercholesterolemic postmenopausal women independent of equol production status, but do not support an independent or additive effect of these particular probiotic bacteria.     

Plasma antioxidant capacity in response to diets high in soy or animal protein with or without isoflavones

BACKGROUND: Several clinical trials have suggested that soy intake decreases oxidative stress. Soy isoflavones have antioxidant properties in vitro, but results of supplementation in clinical trials are inconclusive. OBJECTIVE: The objective was to evaluate the independent effects of soy protein and soy-derived isoflavones on plasma antioxidant capacity and biomarkers of oxidative stress. DESIGN: Forty-two hypercholesterolemic (LDL cholesterol > 3.36 mmol/L) subjects aged >50 y were provided with each of 4 diets in random order in a crossover design. Diets varied in protein source (10% of energy, soy or animal) and isoflavone content (trace or 50 mg/1000 kcal) and were consumed for 42 d each. Plasma antioxidants, protein carbonyls, malondialdehyde, total antioxidant performance, LDL oxidizability, and urinary F(2)-isoprostanes were measured at the end of each dietary phase. RESULTS: Plasma antioxidant concentrations were not significantly different, regardless of dietary treatment, except for isoflavones, which were higher after isoflavone supplementation (P = 0.0001). Although plasma total antioxidant performance was 10% higher with soy protein intake, regardless of dietary isoflavones (P = 0.0003), soy protein did not significantly affect most individual markers of oxidative stress (LDL oxidizability, urinary F(2)-isoprostanes, malondialdehyde, or protein carbonyls in native plasma). However, soy protein was associated with modestly lower concentrations of protein carbonyls in oxidized plasma. There was no significant effect of isoflavones on LDL oxidation, urinary F(2)-isoprostanes, or protein carbonyl groups, although, paradoxically, the plasma malondialdehyde concentration was significantly higher after the isoflavone-rich diets (P = 0.04). CONCLUSIONS: Diets relatively high in soy protein or soy-derived isoflavones have little effect on plasma antioxidant capacity and biomarkers of oxidative stress.     

Effects of soy consumption on gonadotropin secretion and acute pituitary responses to gonadotropin-releasing hormone in women

Soy contains the isoflavone phytoestrogens, genistein and daidzein. These isoflavones are partial estrogen agonists in cell and animal models, but effects from dietary soy in humans are unclear. Experiments were conducted in pre- and postmenopausal women to examine whether dietary isoflavones from soy behave as estrogen agonists, antagonists or have no effect on the estrogen-sensitive pituitary. Pituitary sensitivity to gonadotropin-releasing hormone (GnRH), an estrogen-sensitive endpoint, was measured during GnRH challenge tests administered before, during and after dietary soy consumption. The response to an isoflavone-rich soy food diet was examined in five premenopausal and seven postmenopausal women using transdermal estrogen replacement therapy. Estrogen agonists suppress gonadotropin concentrations and enhance GnRH priming (enhanced gonadotropin secretion in response to repeated doses of GnRH), whereas antagonists elevate gonadotropin concentrations and have no effect on GnRH priming. Each subject consumed 50 g textured soy protein containing 60 mg total isoflavones daily for 10-14 d. Baseline estradiol concentrations were consistent among study periods. In both pre- and postmenopausal women, soy consumption did not affect mean baseline or peak luteinizing hormone (LH) concentrations, indicating a lack of estrogen-like effect at the level of the pituitary. However, in postmenopausal subjects, mean LH secretion decreased after discontinuing soy, suggesting a residual estrogenic effect. In one premenopausal woman, enhanced LH secretion was observed after soy treatment, suggesting there may be subpopulations of women who are highly sensitive to isoflavones.     

Effects of Soy Protein Containing of Isoflavones and Isoflavones Extract on Plasma Lipid Profile in Postmenopausal Women as a Potential Prevention Factor in Cardiovascular Diseases: Systematic Review and Meta-Analysis of Randomized Controlled Trials

The aim of the report was to evaluate the impact of soy protein containing isoflavones and soy isoflavones extract on lipid profile in postmenopausal women, as compared with placebo or protein of milk, casein or isolated soy protein with or without trace isoflavone content. We used the following databases: MEDLINE (PubMed), EMBASE and the Cochrane Library. Quantitative data synthesis was performed by applying a random-effects model. Subgroup analysis and meta-regression were performed to assess the modifiers of treatment response. In total, in the analysis studies, 2305 postmenopausal women took part. Changes in the lipid profile showed statistically significant decreases of total cholesterol by −0.12 (95% CI: −0.21, −0.03) mmol/L, −4.64 (95% CI: −8.12, −1.16) mg/dL, p = 0.01 and increased HDL-cholesterol by 0.03 (95% CI: 0.00, 0.06) mmol/L, 1.15 (95% CI: 0.00, 1.93) mg/dL, p = 0.05, as well as in LDL-cholesterol −0.05 (95% CI: −0.11, 0.01) mmol/L, −1.93 (95% CI: −4.25, 0.39) mg/dL, p = 0.08 and triacylglycerols −0.07 (95% CI: −0.14, 0.00) mmol/L, −6.123 (95% CI: −12.25, 0.00) mg/dL, p = 0.06. Our results suggests that soy and its isoflavones can be effective in correction changes in lipid metabolism in postmenopausal women and may favorably influence in preventing cardiovascular events.     

大豆异黄酮干预对妇女骨密度影响的META分析

目的采用meta分析方法评估大豆异黄酮干预对妇女骨密度作用的随机对照试验研究的合并效应。方法以"植物雌激素"、"异黄酮"、"大豆"、"金雀素黄酮"和"骨"为主题词和关键词,检索1990年1月至2007年10月Medline、Pubmed及CNKI数据库发表的有关文献。纳入文献限定于在成年妇女中进行大豆异黄酮随机对照试验,且有干预前后骨密度值或改变值及其标准差或可信区间者。结果共纳入16篇文献,含1304名妇女,约91%为停经女性。结果发现,平均每天补充73mg异黄酮者的腰椎和总股骨骨密度的年均变化值(95%CI)比对照人群分别增加了18.3(6.0～30.6)和3.3(0.5～6.1)mg/cm2,相当于对应部位骨密度值的2.0%和0.4%;但对股骨颈骨密度无显著效应。亚组分析显示,该效应在干预剂量≥80mg/d者略好于小于80mg/d者;干预时间<1年者略好于≥1年者;剔出非绝经对象可轻微增加合并效应。结论大豆异黄酮干预可有效改善妇女腰椎及总股骨骨密度。     

Beneficial effects of soybean isoflavone supplementation on bone metabolism and serum lipids in postmenopausal japanese women: a four-week study

OBJECTIVE: The aim of this study was to determine the effects of soy isoflavones with weak estrogen-like activities both on bone metabolism and on serum lipids in perimenopausal women. METHODS: Twenty-three healthy perimenopausal women were assigned randomly to either isoflavone or placebo groups. The isoflavone group (n = 12) received daily capsules of soy isoflavone extract (61.8 mg of isoflavones) and the placebo group (n = 11) received daily placebo capsules for four weeks. Urinary excretion of isoflavone was measured at weeks 0, 2 and 4. Urinary excretion of pyridinoline and deoxypyridinoline, bone stiffness and levels of serum cholesterol, triglyceride and cholesterol fractions were measured at weeks 0 and 4. RESULTS: As compared to the placebo group, urinary isoflavone, primarily daidzein, excretion was increased at weeks 2 and 4 in the isoflavone group. Excretion of bone resorption markers was reduced significantly in the isoflavone group. Both total serum cholesterol and LDL cholesterol were decreased significantly in the isoflavone group. Other serum biochemical parameters were not changed in either group. CONCLUSION: Soy isoflavone supplementation for four weeks showed potentially beneficial effects on bone metabolism and on serum lipids in perimenopausal women. These effects could have the potential to reduce the risks of postmenopausal osteoporosis and of cardiovascular diseases in such women.     

The effect of soy consumption on the urinary 2:16-hydroxyestrone ratio in postmenopausal women depends on equol production status but is not influenced by probiotic consumption

Some epidemiologic studies reported an association between a low ratio of urinary 2-hydroxyestrogens (2-hydroxyestradiol + 2-hydroxyestrone) to 16alpha-hydroxyestrone (2:16OHE(1)) and increased breast cancer risk. Some studies show that soy consumption increases this ratio, and it is suggested that this effect may reduce breast cancer risk. We hypothesized that consumption of probiotic bacteria would alter fecal bacteria and enzymes involved in soy isoflavone metabolism, thereby increasing isoflavone bioavailability and enhancing the beneficial effects of soy on estrogen metabolism. Breast cancer survivors (n = 20) and controls (n = 20) were given 4 treatments for 6 wk each, separated by 2-wk washout periods, in a randomized, crossover design: soy protein (26.6 +/- 4.5 g protein/d containing 44.4 +/- 7.5 mg isoflavones/d); soy protein + probiotics (10(9) colony-forming units Lactobacillus acidophilus DDS(R)+1 & Bifidobacterium longum, 15-30 mg fructooligosaccharide/d); milk protein (26.6 +/- 4.5 g protein/d); and milk protein + probiotics. Survivors tended to have a lower baseline urine 2:16OHE(1) ratio than controls (P = 0.10). In the group as a whole, soy consumption tended to increase urinary 2-hydroxyestrogens (P = 0.07) and 16alpha-hydroxyestrone (P = 0.11) but had no effect on the urinary 2:16OHE(1) ratio. When subjects were divided into groups by plasma concentrations and urinary levels of the daidzein metabolite equol, soy increased urinary 2-hydroxyestrogens (P = 0.01) and the 2:16OHE(1) ratio (P = 0.04) only in subjects with high plasma equol concentrations. None of these results were influenced by probiotic consumption. These results are consistent with studies that found lower urine 2:16OHE(1) ratios in women with breast cancer and suggest that soy consumption increases this ratio only in women who are equol producers.     

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.     

Estimated Asian adult soy protein and isoflavone intakes

There is substantial interest in the possible anticancer effects of soy foods. In part, this is because of the historically low incidence rates of breast and prostate cancer in Asia. Of the several putative soybean chemopreventive agents, isoflavones have received the most attention. Awareness of this research has led increasing numbers of consumers to use soy foods, isoflavone-fortified foods, and isoflavone supplements. Therefore, there is a need for guidance regarding appropriate isoflavone intake levels. To this end, this article analyzed soy protein (as a surrogate for isoflavones) and isoflavone intake of the major soy food-consuming countries using individual dietary surveys for the bulk of the information. In total, 24 surveys from 4 countries that met the inclusion criteria were identified: Japan (n = 11), China (n = 7), Hong Kong (n = 4), and Singapore (n = 2). The results indicate that older Japanese adults consume approximately 6-11 g of soy protein and 25-50 mg of isoflavones (expressed as aglycone equivalents) per day. Intake in Hong Kong and Singapore is lower than in Japan, whereas significant regional intake differences exist for China. Evidence suggests that < or =10% of the Asian population consumes as much as 25 g of soy protein or 100 mg of isoflavones per day. The applicability of these findings for making soy intake recommendations for non-Asians is discussed.     

Relation between soy-associated isoflavones and LDL and HDL cholesterol concentrations in humans: a meta-analysis

BACKGROUND: Differences in isoflavone content of soy protein may explain the absence of a dose-response relation between soy protein intake and blood cholesterol concentrations. OBJECTIVE: To study specifically the effect of soy-associated isoflavones on cholesterol concentrations in well-controlled trials substituting soy protein with dairy or animal protein. DESIGN: Studies were identified by MEDLINE searches (1995 - 6 June 2002) and reviewing reference lists. Studies were included if they had a control group or treatment, experimental diets only differed in the amounts of soy protein and isoflavones and were each fed for at least 14 days. A total of 10 studies met these criteria, providing 21 dietary comparisons. SUBJECTS:: Studies comprised 959 subjects (336 men and 623 women), average age ranged from 41 to 67 y and baseline cholesterol concentration from 5.42 to 6.60 mmol/l. INTERVENTIONS: The intake of soy-associated isoflavones increased by 1-95 mg/day and the intake of soy protein increased by 19-60 g/day. RESULTS: Feeding daily 36 g soy protein with 52 mg soy-associated isoflavones on average decreased low-density lipoprotein (LDL) cholesterol by -0.17+/-0.04 mmol/l (mean+/-s.e.) and increased high-density lipoprotein (HDL) cholesterol by 0.03+/-0.01 mmol/l. There was no dose-response relation between soy-associated isoflavones and changes in LDL cholesterol (R=-0.33, P=0.14) (Pearson correlation coefficient) or HDL cholesterol (R=-0.07, P=0.76) or their ratio. CONCLUSIONS: Consumption of soy-associated isoflavones is not related to changes in LDL or HDL cholesterol.     

Plasma phytoestrogens are not altered by probiotic consumption in postmenopausal women with and without a history of breast cancer

Soy phytoestrogens were suggested to reduce the risk of a number of diseases including breast cancer. Given that these compounds are metabolized by bacteria, alteration of intestinal bacteria and enzymes may affect phytoestrogen metabolism. We hypothesized that probiotics, when consumed with soy protein, would increase plasma isoflavones, as well as equol producer frequency, in postmenopausal women. We further hypothesized that these effects would differ between women who have had breast cancer and women who have not. To test these hypotheses, 20 breast cancer survivors and 20 controls completed four 6-wk treatments in a randomized, crossover design: supplementation with soy protein (S) (26.6 +/- 4.5 g protein, 44.4 +/- 7.5 mg isoflavones/d); soy + probiotics (S+P) (10(9) colony-forming units Lactobacillus acidophilus DDS+1 and Bifidobacterium longum, 15-30 mg fructooligosaccharide/d); milk protein (M) (26.6 +/- 4.5 g protein/d); and milk + probiotics (M+P). Plasma phytoestrogen concentrations did not differ between controls and survivors, although genistein tended to be lower in survivors at baseline (P = 0.15), and during soy (P = 0.16) and milk protein (P = 0.16) consumption. As expected, soy consumption increased plasma phytoestrogen concentrations (P < 0.0001). Plasma phytoestrogen concentrations and the number of equol producers did not differ between the S and S+P diets. At the same time, plasma equol concentrations as well as urinary equol excretion in 2 subjects were more than 7-fold different between the 2 diets. These results indicate that this particular probiotic supplement does not generally affect plasma isoflavones, although the large differences between plasma and urinary equol in some subjects suggest that equol producer status may be modifiable in some individuals.     

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.     

One-month exposure to soy isoflavones did not induce the ability to produce equol in postmenopausal women

OBJECTIVE: As more and more postmenopausal women are taking soy isoflavone supplementation for relieving menopausal symptoms, we investigated the impact of chronic exposure on their bioavailability, with focus on achievable plasma concentrations and potential stimulation of the capacity to produce equol.SUBJECTS: A total of 12 Caucasian postmenopausal women. INTERVENTION: Volunteers ingested 100 mg isoflavones/day (aglycone equivalents, in cereal bars and yoghurts) for 1 month. Plasma concentrations of metabolites at 2, 4, 6, 8, 10, 12 and 24 h postdose, as well as urinary excretion in fractions over 36 h were compared between days 1 and 30. RESULTS: Similar plasma kinetic curves were obtained at day 1 and day 30 for genistein and daidzein. Maximum plasma concentrations were 1.68+/-0.68 micromol/l on day 1 compared to 2.27+/-0.76 micromol/l on day 30 for daidzein (P=0.056), and 3.88+/-1.50 micromol/l on day 1 compared to 5.30+/-2.38 micromol/l on day 30 for genistein (P=0.091). Urinary excretion of daidzein and genistein did not differ significantly between days 1 and 30. Maximum plasma concentration of equol increased significantly from 0.31+/-0.27 to 0.99+/-0.51 micromol/l for equol-producer volunteers (P=0.046). However, the seven volunteers who were classified as non-equol producers on day 1 did not acquire the ability to produce equol after 1-month exposure. CONCLUSIONS: Chronic exposure to isoflavones in postmenopausal women resulted in plasma concentrations as high as 2.5-5 micromol/l of each isoflavone, but did not induce the ability to produce equol.     

Role of Isoflavones in the Hypocholesterolemic Effect of Soy

Epidemiologic data suggest an inverse relationship between the consumption of soy isoflavones and cardiovascular disease risk. The aims of this review are to determine if isoflavones play a role in the hypocholesterolemic effect of soy and whether the studies realized with that scope were adequately designed. In humans, most studies have been performed in postmenopausal women. The results are inconsistent, however; some studies show a decrease in total cholesterol and low-density lipoprotein concentrations, and an increase in high-density lipoprotein levels, and other investigations fail to show any beneficial effect of soy isoflavones on lipid profiles. In most studies, beneficial effects could not be attributed with certainty to soy isoflavones. If these components have any health-protecting effect in humans, it is small in comparison with the effect of soy protein itself. There are currently not enough data to recommend the consumption of isoflavone supplements to lower plasma cholesterol levels.     

Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women

BACKGROUND: Controversy exists about the ability of soy protein and isoflavones to modulate vascular reactivity and biochemical cardiovascular disease risk markers in healthy, normolipidemic postmenopausal women. OBJECTIVE: The objective was to investigate whether the consumption of soy protein with isoflavones would result in improved vascular reactivity and decreased biochemical markers of endothelial dysfunction and inflammation, independent of enhanced lipid and antioxidant effects. DESIGN: Healthy postmenopausal women (n = 28) were enrolled in a randomized, double-blind, crossover study, and they consumed 25 g of 3 protein products/d for 6 wk each, with intervening washout periods. The products were isolated soy protein with isoflavones, ethanol-washed isolated soy protein with trace isoflavones, and total milk protein, which supplied 107, 2, and 0 mg total isoflavone (aglycone) units/d, respectively. We studied vascular function by using brachial artery reactivity values, plasma concentrations of vasoactive factors, endothelial inflammatory markers, and plasma isoflavone concentrations. The resistance of whole plasma and isolated LDL to copper-mediated oxidation was measured by conjugated diene formation. RESULTS: Postocclusion peak flow velocity of the brachial artery was significantly (P = 0.03) lower after treatment with isolated soy protein with isoflavones, which is consistent with a vasodilatory response, than after treatment with total milk protein. Plasma isoflavones and metabolites were significantly (P < 0.01) higher after treatment with isolated soy protein with isoflavones. There were no significant changes in biochemical cardiovascular disease risk markers or conjugated diene formation between the 3 dietary groups. CONCLUSION: Daily consumption of soy protein with isoflavones can result in positive vascular effects that are independent of lipid and antioxidant effects in healthy postmenopausal women.     

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.     

Moderate intakes of intact soy protein rich in isoflavones compared with ethanol-extracted soy protein increase HDL but do not influence transforming growth factor beta(1) concentrations and hemostatic risk factors for coronary heart disease in healthy subjects

BACKGROUND: Soybeans contain estrogenic isoflavones that may influence plasma concentrations of transforming growth factor beta(1) (TGF-beta(1)) and plasma lipid and hemostatic risk factors for coronary heart disease. OBJECTIVE: We compared the effects of moderate intakes of soy protein containing intact phytoestrogens (high-isoflavone diet) and soy protein from which most of the phytoestrogens had been extracted (low-isoflavone diet) on active TGF-beta(1) concentrations and plasma lipid and hemostatic risk factors for coronary heart disease. DESIGN: A randomized crossover trial was conducted in 22 young, healthy, normolipidemic subjects (5 men and 17 women) who consumed diets providing 56 or 2 mg isoflavones/d for 17 d each with a 25-d washout period between treatments. Fasting blood samples were obtained on days 13 and 14 of each treatment to measure plasma isoflavone, lipid, fibrinogen, and active TGF-beta(1) concentrations and factor VII coagulant and plasminogen activator inhibitor type 1 activities. RESULTS: Plasma isoflavone concentrations were 100-999 times greater after the high-isoflavone diet than after the low-isoflavone diet (P < 0.05). Plasma HDL-cholesterol and apolipoprotein A-I concentrations were 4% (95% CI: 1%, 8%) and 6% (95% CI: 3%, 10%) higher, respectively, after the high-isoflavone diet than after the low-isoflavone diet (P < 0.01 for both). CONCLUSION: Compared with soy protein from which most of the phytoestrogens have been extracted, soy protein with intact phytoestrogens increases HDL-cholesterol and apolipoprotein A-I concentrations but does not influence LDL-cholesterol, TGF-beta(1), or fibrinogen concentrations; factor VII coagulant activity; or plasminogen activator inhibitor type 1 activity in normolipidemic, healthy subjects.     

Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women

BACKGROUND: Soy-protein consumption is known to reduce plasma total and LDL cholesterol concentrations. However, the responsible soy component or components and the magnitude of effects in normocholesterolemic and mildly hypercholesterolemic subjects are unclear. OBJECTIVE: The present study examined the effects of soy isoflavone consumption on plasma concentrations of triacylglycerol, apolipoprotein (apo) A-I, apo B, lipoprotein(a), and total, LDL, and HDL cholesterol and on LDL peak particle diameter in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. DESIGN: In a randomized crossover trial, fasting plasma samples were obtained from 18 postmenopausal women throughout three 93-d periods of daily isolated soy protein (ISP) consumption providing an average of 7.1 +/- 1.1 (control), 65 +/- 11 (low isoflavone), or 132 +/- 22 (high isoflavone) mg isoflavones/d. RESULTS: Compared with values measured during the control diet, the plasma LDL cholesterol concentration was 6.5% lower (P < 0.02) during the high-isoflavone diet and the ratio of LDL to HDL cholesterol was 8.5% and 7.7% lower during the low- and high-isoflavone diets, respectively (P < 0.02). Isoflavone consumption did not significantly affect plasma concentrations of total or HDL cholesterol, triacylglycerol, apo A-I, apo B, or lipoprotein(a) or the LDL peak particle diameter. CONCLUSIONS: Consumption of isoflavones as a constituent of ISP resulted in small but significant improvements in the lipid profile in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Although the effects were small, it is possible that isoflavones may contribute to a lower risk of coronary heart disease if consumed over many years in conjunction with other lipid-lowering strategies.     

Influence of inulin on plasma isoflavone concentrations in healthy postmenopausal women

BACKGROUND: Bacterial intestinal glucosidases exert an important role in isoflavone absorption. Insoluble dietary fibers such as inulin may stimulate the growth of these bacteria in the colon and, hence, stimulate the absorption of these substances in subjects who may need isoflavone supplementation. OBJECTIVE: The objective was to assess the influence of inulin on plasma isoflavone concentrations after intake of soybean isoflavones in healthy postmenopausal women. DESIGN: Twelve healthy postmenopausal women participated in a randomized, double-blind, crossover study. They consumed 40 mg of a conjugated form of soybean isoflavones (6 mg daidzein and 18 mg genistein as free form) with or without 3.66 g inulin twice daily in two 21-d experimental phases. Blood samples were collected 0, 1, 2, 3, 4, 6, 10, 12, and 24 h after intake of isoflavones with breakfast and dinner at the end of each 21-d experimental phase. Plasma concentrations of isoflavones were assessed by HPLC with an electrochemical detector. RESULTS: Plasma 24-h areas under the curve indicated that the intake of soybean isoflavones with inulin for 21 d was followed by higher plasma concentrations of daidzein and genistein (38% and 91%, respectively) compared with the formulation without inulin. Furthermore, the time for the maximum concentration of daidzein and genistein appeared to be lower after the 21-d intake of soybean isoflavones, with or without inulin. However, the time for the maximum concentration of daidzein and genistein after supplementation with the inulin-containing formulation on day 21 was not significantly different from that after supplementation with the formulation without inulin. CONCLUSIONS: Inulin may increase the apparent plasma concentrations of the soybean isoflavones daidzein and genistein in postmenopausal women. The higher plasma concentrations of the 2 isoflavones suggests that the absorption of each was facilitated by the presence of inulin.