Effects Of Soy Isoflavones Research Articles

Early Life and Adult Exposure to Isoflavones and Breast Cancer Risk

Soy and red-clover isoflavones are commonly consumed within the diet or as a dietary supplement due to a range of presumed beneficial health benefits. These isoflavones are thought to protect against heart diseases as well as breast and other types of cancer. Isoflavones are structurally similar to estrogens and may act as estrogen agonists or antagonists by binding to estrogen receptors. Because of an increased use of isoflavones in processed foods and dietary supplements as well as the greater consumption of soy products, dietary intakes of isoflavones are increasing in children and adolescents in North America. Estrogens are a known component of numerous hormone related cancers including breast cancer. It is with these facts in mind that we review the existing epidemiological and experimental animal studies for a resolution to a proposed correlation between increased isoflavone consumption and breast cancer. There is conflicting evidence from epidemiological, intervention and experimental animal studies regarding the chemopreventing effects of soy isoflavones in breast cancer. Isoflavones are weak estrogens and their effect depends upon the dose, time of exposure and species involved. It would, therefore, not be safe to indisputably accept soy or red-clover as a source of isoflavone resource to prevent breast cancer.

Effects of soy protein and isoflavones on insulin resistance and adiponectin in male monkeys

Isoflavones may influence insulin action by means of their well-known receptor-mediated estrogenic activity. However, isoflavones also bind to peroxisome proliferator–activated receptors (PPARs) that are strongly associated with insulin action. Soy protein with its isoflavones has previously been shown to improve glycemic control in diabetic postmenopausal women and to improve insulin sensitivity in ovariectomized monkeys. The purpose of the current report was to extend our studies of dietary soy protein to male monkeys and determine effects of the soy isoflavones on insulin resistance. Two studies are reported here. Study one involved 91 male monkeys consuming 3 diets differing only by the source of protein (casein-lactalbumin, soy protein with a low isoflavone concentration, or soy protein with a high isoflavone concentration). Intravenous glucose tolerance tests were done, and plasma adiponectin and lipoprotein concentrations were determined after 25 months of study. Samples of visceral fat were obtained at 31 months for assessment of adiponectin and PPAR γ expression. The second study involved 8 monkeys in a Latin-square design that compared the effects of diets with casein/lactalbumin, soy protein with a high isoflavone concentration, or soy protein that was alcohol-washed to deplete the isoflavones. After 8 weeks of treatment, insulin sensitivity and plasma lipoproteins were assessed. At 10 weeks, a biopsy of the skeletal muscle was performed for determination of insulin receptor, PPAR α, and PPAR γ content. The major findings were that consumption of isoflavone-containing soy protein dose-dependently increased insulin responses to the glucose challenge and decreased plasma adiponectin, whereas isoflavone-depleted soy protein decreased body weight and had no effect on plasma adiponectin concentrations. Muscle PPAR α and γ expression was also increased with the isoflavone-depleted soy relative to either casein or soy protein containing the isoflavones. Further studies are needed to determine the mechanisms involved in these effects of a high–soy isoflavone diet and to optimize dietary isoflavone content for maximal health benefits in male subjects.

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

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

The Key Importance of Soy Isoflavone Bioavailability to Understanding Health Benefits

Research over the past two decades has provided significant epidemiological and other evidence for the health benefits of the consumption of soy-based foods. A large number of dietary intervention studies have examined the effects of soy isoflavones on risk factors for cardiovascular disease and hormone-dependent cancers. However, these report large variability in outcome measures, very limited reproducibility between studies, and in some cases, controversy between the results of clinical trials using dietary soy or soy protein and isoflavone supplementation. This highlights a major gap in our understanding of soy isoflavone uptake, metabolism, distribution, and overall bioavailability. There are many potential factors that may influence bioavailability and a better knowledge is necessary to rationalize the inconsistencies in the intervention and clinical studies. This review focuses attention on our current state of knowledge in this area and highlights the importance of metabolism of the parent soy isoflavones and the critical role of gut microbiota on the bioavailability of these compounds and their metabolites.

Protective effects of genistein on proinflammatory pathways in human brain microvascular endothelial cells

Proinflammatory cerebromicrovascular environment has been implicated in the critical early pathologic events in a variety of neurodegenerative diseases. Recent studies also have demonstrated the potential beneficial effects of soy isoflavones. However, cellular and molecular mechanisms underlying these processes are not fully understood. The present study was designed to examine the hypothesis that soy isoflavone genistein may attenuate cytokine-induced proinflammatory pathways in human brain microvascular endothelial cells. The quantitative real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay showed that pretreatment of HBMEC with increasing concentrations of genistein significantly and dose-dependently inhibited cytokine-induced up-regulation of mRNA and protein expression of proinflammatory mediators such as tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1, interleukin-8, and intercellular adhesion molecule-1. In addition, genistein pretreatment significantly reduced cytokine-mediated up-regulation of transmigration of blood leukocytes in a dose-dependent manner. Our results suggest that genistein may attenuate proinflammatory pathways through inhibition of cytokine-induced overexpression of proinflammatory mediators and inflammatory reactions in human brain microvascular endothelial cells.

Effects of soy isoflavones on 17β-estradiol-induced proliferation of MCF-7 breast cancer cells

Based on the results of in vitro-experiments in practically estrogen-free media and in the absence of estrogen-beta receptors, soy isoflavones have been suspected to enhance proliferation of MCF-7 breast cancer cells. In this study the effects of soy isoflavones on MCF-7 cells were investigated in the presence and absence of estrogen, directly and in a metabolized form by testing sera of postmenopausal women supplemented with isoflavones. First, three concentrations of isoflavones (0.1, 1 and 10 mumol/l) were tested at increasing levels of 17-beta-estradiol (<10 pM, 50, 100 and 500 pM). Next, blood sera from women supplemented for two weeks either with 200mg isoflavones or with 2 mg 17-beta-estradiol per day, or the combination of both were investigated in an MCF-7 cell proliferation assay. Further, the samples were screened for changes in gene expression patterns of the MCF-7 cells with Gene Chip arrays. Only at unphysiologically low estrogen levels isoflavones led to minor proliferation-enhancing effects. In contrast, at estradiol levels of >20 pM, isoflavones both tested directly and indirectly (metabolized) revealed significant anti-proliferative effects as well as in the proliferation and the gene chip assay. These findings emphasize the reported advantageous properties of isoflavones for postmenopausal women.

Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones

Objective: To evaluate the effect of soy isoflavones on menopausal symptoms in women who do and who do not produce equol, a daidzein metabolite. Method: A randomized, double-blind, placebo-controlled clinical trial was conducted over 6 months with 96 healthy menopausal women. After taking take 135 mg of isoflavones daily for 1 week, the women in the study group were assigned to the equol-producing (EP) or the non-EP group according to the presence or absence of equol in their urine. Menopausal symptoms were evaluated using a modified Kupperman Index. Result: Compared with the placebo group, the scores for hot flashes and excessive sweating were significantly reduced after 3 months, and the scores for weakness, palpitations, limb paresthesia, and total symptoms after 6 months, in the EP group only. Conclusions: Isoflavone supplementation improves menopausal symptoms only in women with the ability to produce equol.

Soy isoflavone (IF) supplementation appears safe after a two‐year randomized controlled trial (RCT)

Although RCTs quantifying a benefit for menopausal soy IF supplementation abound, few studies have considered the safety of long‐term soy IF intake, particularly when exposure levels are in the form of a tablet, as opposed to food. To evaluate the effect of soy IF on bone loss, 403 early postmenopausal women (54.0±4.0 y) were enrolled in a multi‐site, 2‐year, double‐blind RCT with 1/3 on placebo, 1/3 on 80 mg/d IF and 1/3 on 120 mg/d IF. Baseline characteristics were similar in all groups. The study design focused on safety as a secondary outcome measure and included serum electrolytes, lipids, liver and renal functions, complete blood counts, reproductive and thyroid hormones and cancer (CA) screening. In the supplement groups versus placebo, there was a decrease in free thyroxine (T4) (p=0.024) and an increase in blood urea nitrogen (BUN) (p=0.048), but not thyroid stimulating hormone (p=0.264) or creatinine (p=0.145) after 2 years. Absolute changes in free T4 and BUN were neither outside the normal range nor clinically significant. Major adverse events included one subject with endometrial CA and one with breast CA, which were fewer than predicted in this study population. Soy IF supplementation up to 120 mg/d has no measurable deleterious effect over a 2‐year interval. Supported by Initiative for Future Agriculture and Food Systems Grant 2001‐52102‐11255 USDA CSREES.

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

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

Effects of soy isoflavones on aberrant crypt foci and DNA damage in colon of rats treated with dimethylhydrazine

Soy isoflavones have received considerable attention for the potential role in reducing the risk of cancers. We previously observed significant reduction in the number of colonic aberrant crypt foci and expression of cyclooxygenase‐2 in rats which were fed soy isoflavones after injection of dimethylhydrazine (DMH) for 12 weeks. In this study, we investigated whether feeding soy isoflavones before and during treatment with DMH affects aberrant crypt foci formation and DNA damage in colon. Four weeks old Sprague Dawley male rats were fed AIN93‐based experimental diets supplemented with 0 (control diet), 50 or 500 mg soy isoflavones per kg diet for 8 weeks, and received subcutaneous injections of DMH (20mg/kg body weight) twice per week for 4 weeks while maintaining experimental diets. Then all the groups were given the control diet for another 6 weeks. Colon cells were isolated and subjected to the alkaline single cell gel electrophoresis. DNA damage was determined by measuring tail lengths of the cells with fluorescence microscope. There was no significant difference in weight gains and food efficiencies among groups. Numbers of total aberrant crypts and aberrant crypt foci of colon tended to be lower in the rats pre‐fed soy isoflavones as compared with the control group. DNA damages of colonic cells were insignificant among the groups. Being considered that rats were sacrificed at only 6 weeks after DMH treatment, the results indicate that intake of soy isoflavones before and during DMH treatment may reduce formation of aberrant crypt foci in colon, which was irrelevant to colonic cell DNA damage. This research was supported by RIC program of MCIE.

Fructooligosaccharide and Soy Isoflavone Suppress Colonic Aberrant Crypt Foci and Cyclooxygenase-2 Expression in Dimethylhydrazine-Treated Rats

This study investigated the inhibitory effects of soy isoflavones and fructooligosaccharide (FOS) on colon carcinogenesis. Sprague-Dawley male rats were injected with 1,2-dimethylhydrazine (DMH) and given experimental diets that contained 0%, 3%, 6%, or 9% FOS with or without soy isoflavones (1,000 mg/kg of diet). After 12 weeks, colonic aberrant crypt foci (ACF) formation, cyclooxygenase-2 (COX-2) expression, and fecal bile acid profiles were determined. The numbers of ACF, the numbers of ACF containing four or more crypts per focus of colonic mucosa, and the levels of COX-2 protein in the colonic epithelial tissues were significantly decreased in a dose-dependent manner in the FOS-fed, DMH-treated rats (P < .001), as compared to the DMH-treated control rats. Soy isoflavones significantly decreased the number of ACF with four or more aberrant crypts per focus (P < .001) and the amount of COX-2 protein (P < .01), independently of the effect of the oligosaccharide. The highest suppression of ACF formation was obtained with soy isoflavones combined with >or=6% FOS. No significant relationship was found between the dosage of FOS or soy isoflavones and the concentration of fecal secondary bile acid. We conclude that the combination of FOS and soy isoflavones inhibits colonic ACF formation and reduces COX-2 expression in DMH-treated rats.

Osteoporosis prevention using soy: the OPUS study

Soy isoflavones are believed to have anti‐osteoporotic properties. To evaluate the effect of soy isoflavones on bone loss, 403 early postmenopausal women (54.0±4.0 y) were enrolled in an intent‐to‐treat, multi‐site, 2‐year follow‐up, randomized, double‐blind study with 1/3 on placebo, 1/3 on 80 mg/d of isoflavones, and 1/3 on 120 mg/d of isoflavones along with 1,000 mg/d of CaCO3 and a daily multivitamin with 400 IU of vitamin D. Bone mineral density (BMD) of the whole body (WB), hip and spine and serum bone turnover markers (osteocalcin, bone specific alkaline phosphatase, and cross‐linked N‐telopeptides of type 1 collagen) were measured at baseline and annual intervals. Baseline characteristics were similar in the three groups. A significant protective effect on the decrease in WB BMD was observed with 120 mg/d of soy isoflavones vs. placebo after 1 y (p = 0.027) and 2 y (p = 0.048) of supplementation. No differences were observed in regional BMD measurements or in bone turnover markers. In conclusion, soy isoflavone supplementation reduces the loss of WB BMD at the highest supplementation level, but was not protective at the regional sites. Supported by Initiative for Future Agriculture and Food Systems Grant no. 2001‐52102‐11255 from the USDA CSREES.

Protective effects of soy-isoflavones in cardiovascular disease

Epidemiological studies indicate that the consumption of soy-containing food may prevent or slow-down the development of cardiovascular disease. In endothelial cells application of a soy extract or a combination of the most abundant soy isoflavones genistein and daidzein both inhibited apoptosis, a driving force in atherosclerosis development, when applied in combination with oxidized LDL or homocysteine. Proteome analysis revealed that the stressor-induced alteration of protein expression profile was reversed by the soy extract or the genistein/daidzein mixture. Only few protein entities that could be functionally linked to mitochondrial dysfunction were regulated in common by both application forms of isoflavones. A dietary intervention with isoflavone-enriched soy extract in postmenopausal women, who generally show strongly increased cardiovascular risk due to diminished estrogen production, led to significant alterations in the steady state levels of proteins from mononuclear blood cells. The proteins identified by proteome analysis revealed that soy isoflavones may increase the anti-inflammatory response in blood mononuclear cells thereby contributing to the atherosclerosis-preventive activities of a soy-rich diet. By proteome analysis protein targets were identified in vitro in endothelial cells that respond to soy isoflavones and that may decipher molecular mechanisms through which soy products exert their protective effects in the vasculature.

Lack of Skeletal Effect of Soy Isoflavones in Intact Growing, Female Rats May Be Explained by Constant Serum Estrogenic Activity despite Reduced Serum Estradiol

Background/Aims: Scarce data exist on the effects of soy isoflavones (IF) on bone during peripuberty, a known ‘window of opportunity’ for bone consolidation. Our aim was to determine the skeletal, reproductive, and serum estradiol (E₂)/estrogenic activity response of consuming naturally-occurring soy protein-associated IF during peripuberty. Methods: Weanling (∼3 weeks old), female rats were placed on one of four nutritionally-complete dietary regimens in which protein (200 g/kg diet) was provided as casein or soy protein isolates containing either 0.11 (Low IF), 2.16 (Med IF), or 3.95 (High IF) mg total aglycone isoflavones/g protein for 8 weeks, during which body weights and estrus cycling were recorded. Results: Bone growth and density were unaffected by soy intake while the reproductive tissues showed a slight response (greater uterine weights of the Med and High IF groups). Despite suppression of E₂ concentrations in the High IF group, total circulating estrogenic activity was unaltered. Moreover, in the High IF group, E₂ was significantly depressed compared with bioassayable estrogenic activity, suggesting negative feedback inhibition of E₂ by the elevated circulating levels of IF. Conclusions: This suppression in E₂ with maintenance of total serum estrogenicity in the High IF group may explain the lack of effect observed in the skeletal tissues.

Dietary Soy Isoflavone–Aglycone Lowers Food Intake in Female Rats With and Without Ovariectomy

Estrogens downregulate eating behavior, and soy isoflavones are known to be estrogenic agents. We aimed to examine whether the estrogenic property of soy isoflavones can affect food intake and body weight. Seven-week-old male, female, and ovariectomized (OVX) Sprague-Dawley rats were given free access to a diet containing 100-300 mg total isoflavone/kg diet, or to a control diet, either with or without concurrent administration of estradiol by subcutaneous implantation. Dietary soy isoflavone was shown to lower food intake in female rats, whether or not the animals had undergone ovariectomy. Administration of estradiol lowered the food intake in male rats and in OVX female rats. The decrease in weekly food intake in female rats led to a reduction in their weekly gain in body weight. Dietary soy isoflavone significantly increased the concentration of serum isoflavones, especially equol (a metabolite of daidzein), regardless of gender or ovariectomy. Dietary soy isoflavone did not affect either serum estradiol concentration or uterine and didymus weights, but estradiol administration improved the uterine atrophy in OVX rats, and decreased the didymus weight in male rats. Soy isoflavone lowers the food intake in female rats, but not in the male animals. Contrary to the hypothesis currently in vogue, the reduction in food intake caused by soy isoflavone may not be a purely estrogenic effect. This follows from the finding that the effects of soy isoflavones on food intake and on the reproductive organs differ from the corresponding effects produced by estrogen.

Effects of Dietary and Supplemental Forms of Isoflavones on Thyroid Function in Healthy Postmenopausal Women

Because of the health concerns associated with hormone replacement therapy, many women are seeking alternative therapies. Compounds such as soy isoflavones appear to reduce the risk of some age-related diseases and to lessen the severity of menopausal symptoms. However, concerns regarding harmful effects of soy isoflavones on thyroid function have been reported. This 16-week, double-blinded, placebo-controlled trial evaluated the effects of soy isoflavones on thyroid-stimulating hormone in healthy postmenopausal women. The results of this study suggest that isoflavones obtained from either soymilk or supplements have no effect on thyroid-stimulating hormone in well-nourished postmenopausal women.

Improvement of Bone-Sparing Effect of Soy Isoflavones by Pre- and Probiotics in Postmenopausal women

Background Phytoestrogens consumption is targeted as a possible way to achieve hormonal permeation in postmenopausal women. However, their health effect could depend on their bioavailability. Objectives As phytoestrogens bioavailability could be improved by modulating intestinal microflora, the present study was undertaken to investigate whether isoflavones and pre-or probiotics may improve bone markers. Design An intervention trial (2 months) was carried out on 39 postmenopausal women receiving 100 mg of IF aglycon equivalents daily, incorporated in two jelly milk and two cereal bars. After the first month, the participants were randomised into three treatment groups: soy (control group), soy + fructooligosaccharides (prebiotics group) and soy + yoghurt cultures (probiotics group). Results Level of isoflavone intake was associated with a significant increase in plasma isoflavone levels from baseline to day 15 which was maintained until day 60. Probiotics consumption was associated with increased plasma equol levels at day 60. A 5% increase of bone alkaline phosphatase was elicited on day 30, compared to initial values. Pre- or probiotics did not modulate this parameter. Urinary deoxypyridinoline excretion was slightly increased at day 60. Prebiotics and probiotics consumption improved this parameter. The effect of prebiotics was exacerbated in early compared to late postmenopausal women. Conclusion Addition of prebiotics or probiotics to a diet providing isoflavones is able to improve parameters of bone turnover in early menopause.

Isoflavones as Putative Anti‐aging Food Factors in Asia and Effects of Isoflavone Aglycone‐rich Fermented Soybeans on Bone and Glucose Metabolisms in Post‐menopausal Women

Objective: Since soy isoflavone intake, high in Japanese and Asian populations was epidemiologically associated with lower risks of cardiovascular diseases(CVD), we focused on soy isoflavone effects on other risks of lifestyle-related diseases and investigated whether or not the intake of isoflavone aglycone-rich fermented soybeans affected bone and glucose metabolisms in post-menopausal women. Methods: Healthy post-menopausal women aged 47 to 70 years, 65 in total, were invited to a test diet-placebo independent parallel double-blind dietary intervention study, and were randomized for taking isoflavone aglycone-rich fermented soybean soup (isoflavone aglycone 24 mg/day) or placebo soup for 4 weeks. Blood and 24-hour urine samples were collected before and after the intake. We analyzed the markers of bone and glucose metabolisms. The subjects refrained from consuming other soybean-based foods and isoflavone supplements for 9 weeks, starting at 5 weeks in advance of the intervention. Results: We analyzed 56 subjects from whom complete 24-hour urine samples could be collected, and obtained the following results: 1 Urinary total isoflavone level was significantly higher at 4 weeks in the fermented soybean group (S) than that in the placebo group (P). 2 In P, the urinary excretion of deoxypyridinoline (bone resorption marker) was significantly increased at 4 weeks from the baseline value but did not show any significant change in S. In contrast the serum osteocalcin (bone formation marker) level was significantly increased at 4 weeks from the baseline value in S, but showed no significant change in P. 3 Serum insulin level was significantly lower at 4 weeks in S than in P, while blood glucose levels were similar in S and P. Thus, insulin resistance (the homeostasis model assessment of insulin resistance) was significantly lower at 4 weeks in S than in P. Conclusion: Four-week intake of fermented soybean soup containing 24 mg of isoflavone aglycone improved bone and glucose metabolisms in post-menopausal women, suggesting that the continuous intake of fermented soybeans could prevent bone loss and improve insulin resistance after menopause.

Effects of isoflavones on the coagulation and fibrinolytic system of postmenopausal women

Objective We evaluated the effects of soy isoflavone supplementation on hemostasis in healthy postmenopausal women. Methods In this double-blinded, placebo-controlled study, 47 postmenopausal women 47–66 y of age received 40 mg of soy isoflavone ( n = 25) or 40 mg of casein placebo ( n = 22) once a day for 6 mo. Levels of factors VII and X, fibrinogen, thrombin–antithrombin complex, prothrombin fragments 1 plus 2, antithrombin, protein C, total and free protein S, plasminogen, plasminogen activator inhibitor-1, and D-dimers were measured at baseline and 6 mo. Urinary isoflavone concentrations (genistein and daidzein) were measured as a marker of compliance and absorption using high-performance liquid chromatography. Baseline characteristics were compared by unpaired Student’s t test. Within-group changes and comparison between the isoflavone and casein placebo groups were determined by a mixed effects model. Results The levels of hemostatic variables did not change significantly throughout the study in the isoflavone group; however, the isoflavone group showed a statistically significant reduction in plasma concentration of prothrombin fragments 1 plus 2; both groups showed a statistically significant reduction in antithrombin, protein C, and free protein S levels. A significant increase in D-dimers was observed only in the isoflavone group. Plasminogen activator inhibitor-1 levels increased significantly in the placebo group. However, these changes were not statistically different between groups. Conclusion The results of the present study do not support a biologically significant estrogenic effect of soy isoflavone on coagulation and fibrinolysis in postmenopausal women. However, further research will be necessary to definitively assess the safety and efficacy of isoflavone.

Soy isoflavone supplementation and fasting serum glucose and lipid profile among postmenopausal Chinese women

Long-term effects of soy-derived isoflavones on lipids remain uncertain, and few data are available on their effects on glycemic control. We examined the effects of isolated soy germ isoflavones on the changes in fasting glucose (FG) and lipids. A double-blind, randomized, placebo-controlled trial was conducted in 203 postmenopausal Chinese women aged 48 to 62 years. They were randomly assigned to receive daily doses of 500 mg calcium, and 0 mg isoflavones (placebo, n=67), 40 mg isoflavones (n=68), and 80 mg isoflavones (n=68). Serum FG, triglycerides, high-density lipoprotein, low-density lipoprotein, total cholesterol, and lipoprotein cholesterol were measured at baseline and 1 year after treatment. The primary data analysis was performed on the 203 randomized women according to the intent-to-treat principle. The last value carried forward was used for any missing data at follow-up. We observed moderate but significant favorable effects of soy isoflavones on the changes (P=0.012) and percentage of changes (P=0.031) in FG (analysis of variance). The 1-year mean (SD) differences of FG changes were -5.2 (-9.4 to -1.0) mg/dL (P=0.010) and -3.3 (-7.5 to 0.9) mg/dL (P=0.18) in the 40- and 80-mg isoflavone groups compared with the placebo group. We also noted a significant interaction between the treatment and baseline FG on the changes in FG (P=0.004). The isoflavone effects were much more significant in women with baseline FG 100 mg/dL or more than in those with FG less than 90 mg/dL. We observed little effect of soy isoflavones on changes in serum lipids among the treatment groups. One-year of soy isoflavone supplementation might have a favorable effect on FG in women, but has no significant effect on serum lipids.