Soy Consumption Research Articles

Serum IGF-1 Concentrations Change With Soy and Seaweed Supplements in Healthy Postmenopausal American Women

Insulin-like growth factor 1 (IGF-1) is an anabolic hormone important for growth and development. However, high-circulating serum concentrations in adults are associated with increased risk of postmenopausal breast cancer. Nutritional status and specific foods influence serum IGF-1 concentrations. Breast cancer incidence is typically low in Asian countries where soy is commonly consumed. Paradoxically, soy supplement trials in American women have reported significant increases in IGF-1. Seaweed also is consumed regularly in Asian countries where breast cancer risk is low. We investigated the possibility that seaweed could modify soy-associated increases in IGF-1 in American women. Thirty healthy postmenopausal women (mean age 58 yr) participated in this 14-wk double-blinded, randomized, placebo-controlled crossover clinical trial. Participants consumed 5 g/day placebo or seaweed (Alaria esculenta) in capsules for 7 wk. During the 7th wk, a high-soy protein isolate powder was added (2 mg/kg body weight aglycone equivalent isoflavones). Overnight fasting blood samples were collected after each intervention period. Soy significantly increased serum IGF-1 concentrations compared to the placebo (21.2 nmol/L for soy vs. 16.9 nmol/L for placebo; P = 0.0001). The combination of seaweed and soy significantly reduced this increase by about 40% (21.2 nmol/L for soy alone vs. 19.4 nmol/L; P = 0.01). Concurrent seaweed and soy consumption may be important in modifying the effect of soy on IGF-1 serum concentrations.

Soya protein attenuates abnormalities of the renin–angiotensin system in adipose tissue from obese rats

Several metabolic disturbances during obesity are associated with adipose tissue-altered functions. Adipocytes contain the renin-angiotensin system (RAS), which regulates signalling pathways that control angiogenesis via Akt in an autocrine fashion. Soya protein (Soy) consumption modifies the gene expression pattern in adipose tissue, resulting in an improved adipocyte function. Therefore, the aim of the present work is to study whether dietary Soy regulates the expression of RAS and angiogenesis-related genes and its association with the phosphorylated state of Akt in the adipose tissue of obese rats. Animals were fed a 30% Soy or casein (Cas) diet containing 5 or 25% fat for 160d. mRNA abundance was studied in the adipose tissue, and Akt phosphorylation and hormone release were measured in the primary adipocyte culture. The present results show that Soy treatment in comparison with Cas consumption induces lower angiotensin release and increased insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption varies the expression of RAS and angiogenesis-related genes, which maintain cell size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus, adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken together, these findings suggest that Soy can be used as a dietary strategy to preserve adipocyte functionality and to prevent obesity abnormalities.

Health claims and consumers’ behavioral intentions: The case of soy-based food

This research evaluates the impact of two soy-specific health claims (highlighting FDA approval along with scientific results and simply describing scientific results) on stated behavioral intentions toward soy-based food using a survey administered by Ipsos-Observer to a nationally representative web panel in the summer of 2007. Our research design randomly assigned respondents to a health claim. Three ordered probit models (non-soy users; infrequent soy users; regular soy users) show that non-soy users and infrequent soy users who were exposed to either FDA health claim or general health claim are significantly more likely to eat soy-based food products. FDA or general health claim, however, did not change the behavioral intentions of regular soy users. These results suggest that soy consumption status moderates the impacts of health claims on behavioral intentions. However, the impact of FDA health claim did not differ from that of general health claim, indicating that the word ‘FDA’ did not add any additional information to consumers beyond the general health claim.

Follicle-stimulating hormone levels in female workers exposed to urban pollutants

The aim of this study was to evaluate if there were alterations in FSH plasma levels in female outdoor workers (traffic policewomen and drivers) exposed to chemical urban stressors vs. control group. After excluding subjects with main confounding factors, traffic policewomen, drivers and indoor workers were matched by age, working life, socioeconomic status, marital status, menstrual cycle day, age of menarche, habitual consumption of Italian coffee and soy. A total of 129 female subjects were included in the study: Some 63 workers studied during proliferative phase and 66 during secretory phase of menstrual cycle. Proliferative phase of menstrual cycle: FSH mean values were significantly higher in traffic policewomen compared to controls (p < 0.05). Results suggest that in outdoor workers exposed to urban chemical stressors there are alterations in FSH levels; therefore FSH may be used as an early biological marker, valuable for the group, used in occupational set.

Legumes and soy products consumption and functional disability in older women

Objectives This study was to examine the association between frequency of legumes and soy products consumption and functional disability in older Korean women. Study design Cross-sectional study. Data came from the 2005 Korea National Health and Nutrition Examination Survey (KNHANES). Subjects were 562 women aged 65 years and older living in the community. Main outcome measures Frequency of legume consumption was obtained by using food frequency questionnaire and functional disability was assessed using the instrumental activities of daily living (IADL) and ADL scales. Poisson regression analyses were conducted to examine the association of frequency of legume and soy consumption with functional disability, controlling for covariates. Results Dietary intake of legumes and soy products was associated with a significantly reduced risk of IADL disability after controlling for potential risk factors ( p = 0.002 for trend). Compared with women who consumed legumes and soy products <1 time per week, those who consumed ≥3 times per day had a reduced risk of IADL disability (prevalence ratio = 0.70; 95% confidence interval: 0.51–0.96). In contrast, legumes and soy products consumption was not significantly associated with ADL disability. Conclusions Frequent legumes and soy products consumption was inversely associated with IADL disability in older women. Further studies are needed to clarify the protective effect of legume consumption on functional disability in older people.

Soy Food Consumption and Breast Cancer Prognosis

Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women's Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis. Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.3 years. Isoflavone intakes were measured postdiagnosis by using a food frequency questionnaire. Women self-reported new outcome events semiannually, which were then verified by medical records and/or death certificates. HRs and 95% CIs representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates, using the delayed entry Cox proportional hazards model. As isoflavone intake increased, risk of death decreased (P for trend = 0.02). Women at the highest levels of isoflavone intake (>16.3 mg isoflavones) had a nonsignificant 54% reduction in risk of death. Our study is the third epidemiologic study to report no adverse effects of soy foods on breast cancer prognosis. These studies, taken together, which vary in ethnic composition (two from the United States and one from China) and by level and type of soy consumption, provide the necessary epidemiologic evidence that clinicians no longer need to advise against soy consumption for women with a diagnosis of breast cancer.

Effects of soy intake on glycemic control: a meta-analysis of randomized controlled trials

Evidence from animal and observational studies has supported the beneficial effects of soy intake on glycemic control, but intervention studies in humans have generated mixed results and have not been systematically examined. We aimed to quantitatively evaluate the effects of soy intake on measures of glycemic control. We conducted a structured electronic search of PubMed, EMBASE, the Cochrane Library, and the China National Knowledge Infrastructure (updated to March 2010) databases for randomized controlled trials that described the effectiveness of different soy regimes on measures of glycemic control [homeostatic model assessment of insulin resistance (HOMA-IR) and fasting glucose and insulin, glycated hemoglobin (Hb A(1c)), and 2-h glucose and insulin concentrations]. Data on participants, interventions, outcomes, and potential effect modifiers were extracted independently. Weighted mean effect sizes were calculated for net changes by using fixed-effects or random-effects models. We performed prespecified subgroup analyses to explore the influence of covariates on net changes of fasting glucose and insulin concentrations. Twenty-four trials with a total of 1518 subjects were included in the meta-analysis. Soy consumption did not significantly affect measures of glycemic control. The mean (95% CI) difference was -0.69 mg/dL (-1.65, 0.27 mg/dL) for fasting glucose concentrations in the fixed-effects model (P = 0.16) and -0.18 mg/dL (-0.70, 0.34 mg/dL) for fasting insulin concentrations in the random-effects model (P = 0.50). Significant heterogeneity was noted in the results of fasting insulin concentrations and HOMA-IR. There was not a significant overall effect of soy intake on improvements of fasting glucose and insulin concentrations; however, a favorable change in fasting glucose concentrations was observed in studies that used whole soy foods or a soy diet in the subgroup analysis. Evidence for other glycemic variables such as Hb A(1c) and 2-h postchallenge glucose and insulin concentrations was limited because of the small number of trials.

Effects of Tomato- and Soy-Rich Diets on the IGF-I Hormonal Network: A Crossover Study of Postmenopausal Women at High Risk for Breast Cancer

To determine whether dietary modifications with tomato products and/or a soy supplement affected circulating levels of insulin-like growth factor (IGF)-1 and other markers of cell signaling in postmenopausal women at risk for developing breast cancer. Eligible and consented postmenopausal women at high risk for developing breast cancer were enrolled in a 26-week, two-arm (tomato and soy, 10 weeks each) longitudinal dietary intervention study in which each woman served as her own control. Changes in biochemical endpoints including IGF-I, IGF-binding protein (IGFBP)-3, estradiol, sex hormone-binding globulin (SHBG), C-peptide, and insulin were measured for each intervention arm. Carotenoid and isoflavone levels were measured to assess adherence. Significant increases in carotenoid and isoflavone levels during the tomato and soy study arms, respectively, suggested that women were adherent to both arms of the intervention. The tomato-rich diet had little effect on cell-signaling biomarkers previously associated with breast cancer risk. However, results of the soy intervention showed that concentrations of IGF-I and IGFBP-3 increased by 21.6 and 154.7 μmol/L, respectively (P = 0.001 for both) and SHBG decreased by 5.4 μmol/L (P < 0.001) after consumption of the soy protein supplement. Increased soy protein intake may lead to small, but significant, increases in IGF-I and IGFBP-3. Soy consumption also led to a significant decrease in SHBG, which has been hypothesized to promote, rather than prevent, cancer growth. Previous epidemiologic studies, however, have confirmed protective effect of soy on breast cancer. Additional investigation about the effect of soy on breast cancer risk and its mechanism of action is warranted.

Highlights of This Issue

Breast cancer incidence rates among U.S. non-Hispanic white women decreased by ∼7% between 2002 and 2003, related to a drop in postmenopausal hormone therapy use. Although several studies have reported that breast cancer incidence rates have continued to decline, none of these studies exclusively examined the trend after 2003. To address this, DeSantis and colleagues examined SEER registries from 2000 to 2007 and National Health Interview Survey data from 2003, 2005, and 2008. They report that the sharp decline in breast cancer incidence rates among non-Hispanic white woman that occurred between 2002 and 2003 did not continue through 2007, although hormone therapy use continued to decrease. Future studies will be necessary to better understand these breast cancer trends.The low incidence of sarcomas makes it difficult to discern heritable risks for any individual sarcoma subtype. To overcome this, Jones and colleagues grouped cases from the Utah Cancer Registry and the Utah Population Database as either complex genotype/karyotype sarcomas or balanced translocation sarcomas to calculate risks for relatives of sarcoma patients. Although there was no evidence for excess relatedness for the balanced translocation sarcomas, there was strong familiarity among complex genotype sarcomas. This study indicates that genetics may play a key role in complex genotype sarcomagenesis.Gastric cancer incidence in African Americans is twice that of whites, and differing prevalence of Helicobacter pylori (H. pylori) isolates may explain the disparity. To explore this, Epplein and colleagues assessed serum levels of antibodies against different H. pylori proteins as well as African and European admixtures in African American and white study participants. African American race was associated with 2- to 6-fold increased odds for the presence H. pylori proteins. Compared with whites, African Americans with “high” African ancestry had 5.2-fold increased odds of H. pylori sero-positivity. Among African Americans, “high” African ancestry had 3.4-fold increased odds of H. pylori sero-positivity. These results provide a framework for better detection and prevention of gastric cancer in African Americans.Although earlier clinical studies suggested that soy may promote breast tumor growth, recent studies demonstrate that soy-containing foods are not adversely related to breast cancer prognosis. To examine this, Caan and colleagues used data from the Women's Healthy Eating and Living (WHEL) study to examine the effect of soy intake on breast cancer prognosis. They found that as soy intake increased, risk of death decreased. This study provides further evidence that clinicians no longer need to advise against soy consumption for women diagnosed with breast cancer.

Validation of self-reported anthropometrics in the Adventist Health Study 2

BackgroundRelying on self-reported anthropometric data is often the only feasible way of studying large populations. In this context, there are no studies assessing the validity of anthropometrics in a mostly vegetarian population. The objective of this study was to evaluate the validity of self-reported anthropometrics in the Adventist Health Study 2 (AHS-2).MethodsWe selected a representative sample of 911 participants of AHS-2, a cohort of over 96,000 adult Adventists in the USA and Canada. Then we compared their measured weight and height with those self-reported at baseline. We calculated the validity of the anthropometrics as continuous variables, and as categorical variables for the definition of obesity.ResultsOn average, participants underestimated their weight by 0.20 kg, and overestimated their height by 1.57 cm resulting in underestimation of body mass index (BMI) by 0.61 kg/m2. The agreement between self-reported and measured BMI (as a continuous variable), as estimated by intraclass correlation coefficient, was 0.97. The sensitivity of self-reported BMI to detect obesity was 0.81, the specificity 0.97, the predictive positive value 0.93, the predictive negative value 0.92, and the Kappa index 0.81. The percentage of absolute agreement for each category of BMI (normoweight, overweight, and obese) was 83.4%. After multivariate analyses, predictors of differences between self-reported and measured BMI were obesity, soy consumption and the type of dietary pattern.ConclusionsSelf-reported anthropometric data showed high validity in a representative subsample of the AHS-2 being valid enough to be used in epidemiological studies, although it can lead to some underestimation of obesity.

The soy isoflavone genistein alters cell growth in non‐malignant colonocytes

Numerous studies show that consumption of soy and its primary phytoestrogen genistein (Gen) can inhibit the formation of colon tumors. However, the effect of Gen at dietary levels in non-diseased colonocytes has not been investigated. The presented studies focused on evaluating the effects of Gen in non-malignant colonocytes in vitro and in vivo to determine how the compound influences the physiology of these cells. Gen treatments (1 and 10 μM/L) decreased cell growth, increased apoptosis, and increased p53 transcriptional activity in young adult mouse colonocytes (YAMC), a non-transformed cell line. However, these effects were lost when co-treated with an estrogen receptor beta (ERβ) antagonist. To further study the effects of Gen in healthy colonic epithelia, we evaluated physiologic changes in colonic crypts in ovariectomized mice given an Estradiol (E2) pellet, 1,000 ppm Gen diet, or a phytoestrogen free diet. As seen in vitro, E2 treated animals had significantly higher rates of apoptosis with Gen trending in the same fashion. These data demonstrate that Gen alters the physiology of non-malignant colonocytes which appears to be mediated through ERβ. Collectively, with our previous data, this suggests that Gen influences colonocyte physiology and this state may partially explain how this compound decreases risk of colon cancer. Grant support: American Institute for Cancer Research grant 07B080. Grant Funding Source: American Institute for Cancer Research grant 07B080

Hypogonadism and erectile dysfunction associated with soy product consumption

Previous research has focused on the beneficial effects of soy and its active ingredients, isoflavones. For instance, soy consumption has been associated with lower cardiovascular and breast cancer risks. However, the number of reports demonstrating adverse effects of isoflavones due to their estrogenlike properties has increased. We present the case of a 19-y-old type 1 diabetic but otherwise healthy man with sudden onset of loss of libido and erectile dysfunction after the ingestion of large quantities of soy-based products in a vegan-style diet. Blood levels of free and total testosterone and dehydroepiandrosterone (DHEA) were taken at the initial presentation for examination and continuously monitored up to 2 y after discontinuation of the vegan diet. Blood concentrations of free and total testosterone were initially decreased, whereas DHEA was increased. These parameters normalized within 1 y after cessation of the vegan diet. Normalization of testosterone and DHEA levels was paralleled by a constant improvement of symptoms; full sexual function was regained 1 y after cessation of the vegan diet. This case indicates that soy product consumption is related to hypogonadism and erectile dysfunction. To the best of our knowledge, this is the first report of a combination of decreased free testosterone and increased DHEA blood concentrations after consuming a soy-rich diet. Hence, this case emphasizes the impact of isoflavones in the regulation of sex hormones and associated physical alterations.

Effects of Dietary Soy Intake on Maternal Thyroid Functions and Serum Anti-Thyroperoxidase Antibody Level During Early Pregnancy

Soy and its isoflavones have been suggested to suppress thyroperoxidase (TPO), induce goiter, inhibit deiodinase, and modulate immune functions. This study initially investigated the effects of dietary soy consumption on maternal thyroid functions and anti-TPO antibody (TPOAb) production during early pregnancy. Data were collected through questionnaire from 505 women enrolled during early pregnancy by random sampling in Shenyang, China. Based on soy intake frequency, the subjects were divided into three groups (frequent [three or more times per week], conventional [more than twice per month but less than three times per week], and occasional [two or fewer times per month]). Serum thyrotropin (TSH), free thyroxine (FT(4)), and TPOAb were measured by chemiluminescence immunoassay. Additionally, the concentrations of two primary isoflavones (daidzein and genistein) and creatinine were assessed in the spot urine samples from representative subjects (about 20%) randomly selected from the three groups. The percentages of frequent, conventional, and occasional consumers were 18.6%, 62.6%, and 18.8%, respectively. No difference was found in age, medical records, family history of thyroid diseases, serum FT(4), TSH, and TPOAb levels, TPOAb-positive percentages, or prevalence of thyroid dysfunctions among the groups. Both urinary daidzein and genistein levels were significantly higher in the frequent consumers compared with the other two groups. No correlations were found between urinary isoflavone levels and serum FT(4) or TSH. Urinary isoflavone levels were not significantly different between TPOAb-positive and -negative women among the randomly selected representative subjects. On the whole, our findings suggest dietary soy consumption during early pregnancy is not associated with the development of thyroid dysfunction or autoimmunity.

The effect of dietary soy isoflavones before and after ovariectomy on hippocampal protein markers of mitochondrial bioenergetics and antioxidant activity in female monkeys

Estrogen therapy can promote cognitive function if initiated within a ‘critical window’ during the menopausal transition. However, in the absence of a progestogen, estrogens increase endometrial cancer risk which has spurred research into developing estrogenic alternatives that have the beneficial effects of estrogen but which are clinically safer. Soy protein is rich in isoflavones, which are a class of potential estrogenic alternatives. We sought to determine the effects of two diets, one with casein-lactalbumin as the main protein source and the other with soy protein containing isoflavones, on protein markers of hippocampal bioenergetic capacity in adult female cynomolgus macaques ( Macaca fascicularis). Further, we assessed the effects of dietary soy isoflavones before or after ovariectomy. Animals receiving soy diet premenopausally then casein/lactalbumin post-ovariectomy had higher relative hippocampal content of glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase and pyruvate dehydrogenase subunit e1α. Post-ovariectomy consumption of soy was associated with higher succinate dehydrogenase α levels and lower levels of isocitrate dehydrogenase, both proteins involved in the tricarboxylic acid cycle, significantly decreased expression of the antioxidant enzyme peroxiredoxin-V, and a non-significant trend towards decreased manganese superoxide dismutase expression. None of the diet paradigms significantly affected expression levels of oxidative phosphorylation enzyme complexes, or of mitochondrial fission and fusion proteins. Together, these data suggest that long-term soy diet produces minimal effects on hippocampal expression of proteins involved in bioenergetics, but that switching between a diet containing primarily animal protein and one containing soy isoflavones before and after menopause may result in complex effects on brain chemistry.

Soy consumption and breast cancer risk: four recent meta-analyses

Soy consumption and breast cancer risk: four recent meta-analyses

South African consumers' opinions and beliefs regarding the health benefits of soy and soy products

AbstractStudies linking diet and health and consumers' demand for health information, has led to an increasing awareness of the role of nutrition in health and disease. Interest in soy foods and an awareness of its health benefits has also increased. The objective was to assess South African (SA) consumers' opinions and beliefs regarding the health benefits of soy and soy products using different statements.This cross‐sectional study randomly selected 3001 respondents from metropolitan and rural areas in South Africa. Data of 81% of respondents (n = 2437), who had heard of soy, were used. Trained fieldworkers administered questionnaires as face‐to‐face interviews. Fifteen statements probing consumers' opinions regarding the health benefits of soy were used. The data were weighted to be representative of the total South Africa adult population (n = 18 251 000) based on gender, age, living environment and race distribution in 2000.Effect sizes were used to determine the strength of associations (practical significance), since statistical significance could be attributed to the large study population. No practically significant differences between either gender or age groups, or between rural and metropolitan respondents' opinions were found. Most respondents in the total study population (50–75%), as well as within all race groups agreed that soy has many health benefits; soy is good for you; soy lowers cholesterol; soy is good for people with a milk allergy; soy helps keep your heart healthy; soy is good for diabetes and soy is good for growing children. Medium to large practically significant differences were found between racial groups regarding some of the statements. Practically significantly more adult Black consumers believed that soy is only for people with a low‐income, and fewer that soy milk is good for people with a milk allergy than did White, Indian and Coloured consumers. Whites were relatively more positive towards the use of soy for people with a milk allergy opposed to Blacks, while Blacks were relatively more positive than Whites towards the statement that soy helps keep your bones strong.The results indicate that SA consumers held positive opinions and associate consumption of soy with several health benefits. The role of soy is seen more as being preventative than curative. It may represent a challenge to the food industry to design soy‐containing products that appeal to a broader spectrum of consumers.

Enhanced Expression and Glucocorticoid-Inducibility of Hepatic Cytochrome P450 3A Involve Recruitment of the Pregnane-X-Receptor to Promoter Elements in Rats Fed Soy Protein Isolate

Previous studies and Expt. 1 of the current study demonstrate that diets made with soy protein isolate (SPI) enhance the glucocorticoid-inducibility of hepatic cytochrome P450 (CYP)3A-dependent monooxygenase activities (P < 0.05) compared with diets made with casein (CAS). To determine the underlying molecular mechanism, in a second experiment, we analyzed the time course of dexamethasone (DEX)-induction of hepatic CYP3A mRNA expression on postnatal d (PND) 25 and PND60 in male and female rats fed SPI- or CAS-based diets. After 50 mg/kg DEX, CYP3A1 mRNA expression increased >200-fold in SPI-fed males and females at PND25 compared with a 100-fold increase in CAS-fed rats (P < 0.05). The DEX-induced increase in CYP3A1 mRNA in SPI-fed rats on PND60 was also greater than that in CAS-fed rats. The induction by DEX of CYP3A2 mRNA was 1- to 3-fold greater in rats fed SPI compared with those fed CAS on PND25 (P < 0.05). Quantitation of newly synthesized CYP3A1 RNA transcripts by nuclear run-on analysis demonstrated a greater rate of basal transcription in SPI-fed compared with CAS-fed rats on PND60 accompanied by greater binding of the pregnane X receptor (PXR) to a response element on the CYP3A1 promoter in SPI-fed compared with CAS-fed rats (P < 0.05). These data suggest that increased hepatic CYP3A expression and inducibility following SPI feeding involves recruitment of PXR to its response element and suggests that soy consumption has potential effects on metabolism and transport of a wide variety of drugs and on bile acid homeostasis via proteins regulated by this transcription factor.

Influence of diet on nipple aspirate fluid production and estrogen levels

One possible mechanism how nutritional factors may affect breast cancer risk is through an influence on estrogen levels. Nipple aspirate fluid (NAF) is thought to provide a more direct insight into hormonal influences on breast tissue than serum. The ability to produce NAF may be an indicator of breast cancer risk. The current analysis was conducted as part of a soy trial in 92 premenopausal women and evaluated the relation of usual dietary intake with NAF volume and the most predominant steroidal estrogens in NAF and serum at baseline. Estradiol (E(2)) and estrone sulfate (E(1)S) were assessed in NAF and E(2), estrone (E(1)), and E(1)S, in serum using highly sensitive radioimmunoassays. The statistical analysis applied multivariate, log-linear regression models. Intake of saturated fat and cheese (p = 0.06 for both) indicated a positive trend with NAF volume whereas isoflavonoid and soy consumption suggested inverse associations (p = 0.01 and p = 0.08). For estrogens in NAF, total fat and monounsaturated fat intake was positively associated with E(2) (p = 0.05 and p = 0.02) and in serum, alcohol intake was associated with higher E(1)S levels (p = 0.02). These findings suggest a weak influence of dietary composition on NAF production and estrogen levels in serum and NAF.

Soy isoflavone genistein induces cell death in breast cancer cells through mobilization of endogenous copper ions and generation of reactive oxygen species

Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high isoflavone intake through soy consumption have lower rates of breast, prostate, and colon cancer. Isoflavone genistein in soybean is considered a potent chemopreventive agent against cancer. Although several mechanisms have been proposed, a clear anticancer action mechanism of genistein is still not known. Here, we show that the cytotoxic action of genistein against breast cancer cells involves mobilization of endogenous copper. Further, whereas the copper specific chelator neocuproine is able to inhibit the apoptotic potential of genistein, the molecules which specifically bind iron (desferroxamine mesylate) and zinc (histidine) are relatively ineffective in causing such inhibition. Also, genistein-induced apoptosis in these cells is inhibited by scavengers of reactive oxygen species (ROS) implicating ROS as effector elements leading to cell death. As copper levels are known to be considerably elevated in almost all types of cancers, in this proof-of-concept study we show that genistein is able to target endogenous copper leading to prooxidant signaling and consequent cell death. We believe that such a mechanism explains the anticancer effect of genistein as also its preferential cytotoxicity towards cancer cells.

Abstract CN06-02: Soy foods and cancer risk: How does the relation vary in individuals with different ethnicity, diet, and lifestyle?

Abstract Soy foods have been part of traditional Asian diets for many centuries, while soy products were introduced in Western countries only a few decades ago. Migrants from Asia maintained their food habits to a certain degree when they moved to the U.S., but they also adopted Western foods (1). Inspired by studies among migrants and by the low incidence rates for several cancers among Asians, research into the protective effects of isoflavones in soy foods was initiated. Due to their estrogen-like structure, much of the research has focused on hormone-dependent cancers, i.e., breast, endometrial, ovarian, and prostate cancer, but some work on colorectal cancer has also been performed. During years of experimental and epidemiologic research, it has become evident that not all populations may derive the same benefit from consuming soy foods. One of the more consistent findings in soy research is the fact that epidemiologic studies report a stronger protective effect of soy foods against breast cancer among women who grew up in Asian countries and in those who consumed soy foods throughout childhood and adolescence (2). This presentation will focus on epidemiologic studies that have investigated the association between soy foods and cancer risk among populations with different ethnic backgrounds. In addition, some underlying mechanisms that may be responsible for ethnic differences, such as intestinal equol production, genetic polymorphisms, and timing of exposure will be discussed. Epidemiologic studies among women of Asian, primarily Japanese and Chinese, ancestry show a more consistent protective effect against breast cancer than investigations among Western populations; the odds ratio (OR) was 0.71 (95% CI: 0.60-0.85) among Asians when the highest and lowest intake group were compared, while soy food was unrelated to breast cancer risk in Western studies (OR = 1.04; 95%CI: 0.97-1.11) (2). Similarly, a meta-analysis of prostate cancer studies found a lower risk associated with soy consumption only among Asian (OR = 0.52; 95%CI: 0.33-0.81) but not Western populations (OR = 0.99; 95% CI: 0.85-1.16) (3). On the other hand, meta-analyses for endometrial, ovarian, and colorectal cancer described only small differences in associations by ethnicity (4, 5). Recent case-control analyses nested within the Multiethnic Cohort in Hawaii and Los Angeles examined urinary isoflavone excretion as a biomarker of soy intake and reported similar results for breast but not prostate cancer. While the risk associated with breast cancer was 0.69 (95% CI: 0.51-0.92) among Japanese Americans and 0.98 (95% CI: 0.61-1.55) among Caucasians (6), the risk estimates did not differ by ethnicity for prostate cancer (7). Evidence from observational and intervention studies also suggests possible differential effects of soy intake on biomarkers of breast cancer risk (8-10), e.g., mammographic density and concentrations of serum estrogens and testosterone, urinary estrogen metabolite patterns, IGF-I, and PSA. Whereas the higher intake and possibly the type of soy foods in Asian populations may explain the observations for breast and prostate cancer risk (11), bioavailability of bioactive substances may also be a contributing factor (12). For example, the capacity of the intestinal bacteria to metabolize the isoflavone dadzein into the metabolite equol varies across populations and may confer a greater protection against disease than the other isoflavonoids (13, 14). Another reason that not all individuals may benefit from soy food exposure to the same degree is genetic variation. Genetic polymorphisms may alter enzyme activity or modulate the expression of genes involved in pathways influenced by isoflavones and relevant to cancer risk. Menopausal status, obesity, and other dietary components are other causes for isoflavones to exert differential actions across populations. Alternatively, the overall effect of soy foods on carcinogenesis may depend on the time of life when isoflavones were administered because isoflavones have estrogenic and anti-estrogenic effects. A number of case-control studies that assessed soy intake during childhood or adolescence found a stronger protection for early life than adult soy intake. Since experimental studies indicate that estrogen exposure in young animals induces protection against cancer development, the weak estrogenic effects of isoflavones in soy beans, if consumed early in life, may achieve or accelerate differentiation of breast tissue structures similar to an early pregnancy and, thereby, make the tissue less susceptible to carcinogens and prevent tumor development later in life. Since the reports about beneficial effects of soy against cancer come primarily from Asian populations who have consumed soy foods since childhood and whose diet and lifestyle differs in many other ways from Western countries, the expectations of individuals in Western countries who start eating soy products later in life may not be fulfilled. Therefore, future research in different populations should focus on how soy affects cancer risk throughout life.