Soy foods and urinary isoprostanes: results from a randomized study in premenopausal women.
ABSTRACT: In addition to their antiestrogenic effects, soy isoflavones may protect against cancer through alternate biological actions, for example, antioxidant properties. This randomized crossover study explored the relationship between dietary isoflavone intake through common soy foods and oxidative stress quantified by urinary isoprostane levels. Eighty-two women aged 39.2 ± 6.1 years were randomly selected to receive a high soy diet of 2 soy food servings per day and a low soy diet of <3 servings per week for 6 months each, separated by a 1-month washout period. Urine samples were collected at baseline and at the end of each dietary period. Urinary isoprostane levels were measured using enzyme-linked immunosorbent assays (ELISA) and adjusted for creatinine levels. Mixed models using log-transformed values were applied to evaluate the effect of the high soy diet. Unadjusted isoprostane excretion levels were lower during the high rather than the low soy diet, but this effect was not statistically significant (p = 0.81). After adjustment for urinary creatinine, isoprostane excretion was slightly higher during the high soy diet (p = 0.02), an observation that was confirmed in a regression analysis between urinary isoflavones and isoprostanes during the high soy diet. The original association remained significant when restricted to adherent participants, however this effect disappeared after exclusion of three extreme values. In agreement with several previous reports, these findings do not support the hypothesis that soy exerts antioxidant effects, as measured by urinary isoprostane excretions, but additional markers of oxidative stress need to be investigated in future studies.
Project description:We evaluated urinary isoflavonoid excretion as a biomarker of dietary isoflavone intake during two randomized soy trials (13-24 months) among 256 premenopausal women with a total of 1,385 repeated urine samples. Participants consumed a high-soy diet (2 servings/day) and a low-soy diet (<3 servings/week), completed 7 unannounced 24-hour dietary recalls, and donated repeated urine samples, which were analyzed for isoflavonoid excretion by liquid chromatography methods. We computed Spearman correlation coefficients and applied logistic regression to estimate the area under the curve. Median overall daily dietary isoflavone intakes at baseline, during low- and high-soy diet were 2.3, 0.2, and 60.4 mg aglycone equivalents, respectively. The corresponding urinary isoflavonoid excretion values were 0.4, 1.0, and 32.4 nmol/mg creatinine. Across diets, urinary isoflavonoid excretion was significantly associated with dietary isoflavone intake (rs=0.51, AUC=0.85; p<0.0001) but not within diet periods (rs=0.05-0.06, AUC=0.565-0.573). Urinary isoflavonoid excretion is an excellent biomarker to discriminate between low- and high-soy diets across populations, but the association with dietary isoflavone intake is weak when the range of soy intake is small.
Project description:One of the hypothesized protective mechanisms of soy against breast cancer involves changes in estrogen metabolism to 2-hydroxy (OH) and 16?-OH estrogens. The current analysis examined the effect of soy foods on the 2:16?-OH E(1) ratio among premenopausal women during a randomized, crossover intervention study; women were stratified by equol producer status, a characteristic thought to enhance the protective effects of soy isoflavones. The study consisted of a high-soy diet with 2 soy food servings/day and a low-soy diet with <3 servings of soy/wk for 6 mo each; estrogen metabolites were measured in 3 overnight urines (baseline and at the end of the low- and high-soy diet) using gas chromatography mass spectrometry for the 82 women who completed the study. Urinary isoflavonoids were assessed by liquid chromatography mass spectrometry. When applying mixed models, the 2:16?-OH E(1) ratio increased (P = 0.05) because of a nonsignificant decrease in 16?-OH E(1) (P = 0.21) at the end of the high-soy diet. Similar nonsignificant increases in the 2:16?-OH E(1) ratio were observed in equol producers (P = 0.13) and nonproducers (P = 0.23). These findings suggest a beneficial influence of soy foods on estrogen metabolism regardless of equol producer status.
Project description:<h4>Unlabelled</h4>Soy isoflavones and their metabolism by intestinal microbiota have gained attention because of potential health benefits, such as the alleviation of estrogen/hormone-related conditions in postmenopausal women, associated with some of these compounds. However, overall changes in gut bacterial community structure and composition in response to addition of soy isoflavones to diets and their association with excreted isoflavone metabolites in postmenopausal women has not been studied. The aim of this study was to determine fecal bacterial community changes in 17 postmenopausal women after a week of diet supplementation with soy bars containing isoflavones, and to determine correlations between microbial community changes and excreted isoflavone metabolites. Using DGGE profiles of PCR amplified 16S rRNA genes (V3 region) to compare microbial communities in fecal samples collected one week before and one week during soy supplementation revealed significant differences (ANOSIM p<0.03) before and after soy supplementation in all subjects. However, between subjects comparisons showed high inter-individual variation that resulted in clustering of profiles by subjects. Urinary excretion of isoflavone (daidzein) metabolites indicated four subjects were equol producers and all subjects produced O-desmethylangolensin (ODMA). Comparison of relative proportions of 16S rRNA genes from 454 pyrosequencing of the last fecal samples of each treatment session revealed significant increases in average proportions of Bifidobacterium after soy consumption, and Bifidobacterium and Eubacterium were significantly greater in equol vs non-S-(-)equol producers. This is the first in vivo study using pyrosequencing to characterize significant differences in fecal community structure and composition in postmenopausal women after a week of soy diet-supplementation, and relate these changes to differences in soy isoflavones and isoflavone metabolites.<h4>Trial registration</h4>Clinicaltrials.gov NCT00244907.
Project description:Based on the hypothesis that soy food consumption may influence breast tissue activity, we examined its effect on the production of nipple aspirate fluid (NAF), a possible indicator of breast cancer risk. Of 310 premenopausal women screened, 112 (36%) produced at least 10 ?L of NAF, the minimum for study participation. In a crossover design, we randomized 96 women to 2 groups who, in reverse order, consumed a high-soy diet with 2 soy servings/d (1 serving = 177 mL soy milk, 126 g tofu, or 23 g soy nuts) and a low-soy diet with <3 servings/wk of soy for 6 mo each separated by a 1-mo washout period. During each diet period, 3 NAF samples were obtained (baseline and 3 and 6 mo) using a FirstCyte Aspirator and 4 urine samples (baseline and 1, 3, and 6 mo) were analyzed for isoflavonoids by liquid chromatography tandem MS. Adherence to the study protocol according to 24-h dietary recalls and urinary isoflavonoid excretion was high. The drop-out rate was 15% (n = 14); 82 women completed the intervention. The 2 groups produced similar mean NAF volumes at baseline (P = 0.95) but differed in age and previous soy intake and in their response to the intervention (P = 0.03). In both groups, NAF volume decreased during the first 3 mo of the high-soy diet period and returned to baseline at 6 mo, but there was no effect of the high-soy diet on NAF volume (P = 0.50 for diet; P-interaction = 0.21 for diet with time). Contrary to an earlier report, soy foods in amounts consumed by Asians did not increase breast tissue activity as assessed by NAF volume.
Project description:We studied urinary riboflavin as an objective biomarker of compliance in clinical research using a simplified method amenable to high throughput analysis. Six healthy women not taking vitamin supplements ingested a study pill containing riboflavin (32 mg) as an inactive tracer and the soy isoflavones daidzin (0.243 mmole) and genistin (0.222 mmole) as active ingredients once daily for four days. Riboflavin and metabolites of the isoflavones were measured in urine samples obtained before and after each pill. Urinary excretion of riboflavin and metabolites of both isoflavones peaked within 8 hrs and remained higher than baseline for 24 hrs. Urinary excretion of riboflavin was also measured in 152 additional women with unrestricted dietary supplement intakes. Mean and median urinary riboflavin concentrations in these women were 0.42 and 0.31 ?g/mL, respectively, compared to 0.2 ?g/mL during a riboflavin-restricted diet. Receiver operating characteristics (ROC) curves indicated that urinary riboflavin within 24 hrs after a 32 mg dose would perform well as a measure of compliance (all areas under the ROC curves ?0.84. Samples collected during the initial 8 hrs after pill ingestion performed better as a compliance measure than later collections. In summary, compliance in a clinical study can be monitored in real time by incorporating 32 mg of riboflavin into study pills, with compliance indicated by urinary riboflavin levels increasing over individual baselines or to ?1.0 ?g/mL, with a false positive rate of being classified as compliant at <5%.
Project description:While epidemiologic studies suggest that soy intake early in life may reduce breast cancer risk, there are also concerns that exposure to soy isoflavones during childhood may alter pubertal development and hormonal profiles. Here, we assessed the effect of a high-soy diet on pubertal breast development, sex hormones, and growth in a nonhuman primate model. Pubertal female cynomolgus monkeys were randomized to receive a diet modeled on a typical North American diet with one of two protein sources for approximately 4.5 years: (i) casein/lactalbumin (CL, n = 12, as control) or (ii) soy protein isolate with a human equivalent dose of 120 mg/d isoflavones (SOY, n = 17), which is comparable to approximately four servings of soy foods. Pubertal exposure to the SOY diet did not alter onset of menarche, indicators of growth and pubertal progression, or circulating estradiol and progesterone concentrations. Greater endometrial area was seen in the SOY group on the first of four postmenarchal ultrasound measurements (P < 0.05). There was a subtle effect of diet on breast differentiation whereby the SOY group showed higher numbers of differentiated large-sized lobular units and a lower proportion with immature ducts following menarche (P < 0.05). Numbers of small lobules and terminal end buds and mammary epithelial cell proliferation did not differ by diet. Expression of progesterone receptor was lower in immature lobules of soy-fed animals (P < 0.05). Our findings suggest that consumption of soy starting before menarche may result in modest effects consistent with a more differentiated breast phenotype in adulthood.
Project description:<h4>Background</h4>Soy and red clover isoflavones are controversial due to purported estrogenic activity and possible effects on breast cancer. We conducted a systematic review of soy and red clover for efficacy in improving menopausal symptoms in women with breast cancer, and for potential impact on risk of breast cancer incidence or recurrence.<h4>Methods</h4>We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to March 2013 for human interventional or observational data pertaining to the safety and efficacy of soy and red clover isoflavones in patients with or at risk of breast cancer.<h4>Results</h4>Of 4179 records, we included a total of 131 articles: 40 RCTs, 11 uncontrolled trials, and 80 observational studies. Five RCTs reported on the efficacy of soy for hot flashes, showing no significant reductions in hot flashes compared to placebo. There is lack of evidence showing harm from use of soy with respect to risk of breast cancer or recurrence, based on long term observational data. Soy intake consistent with that of a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence. Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues. Prospective data of soy use in women taking tamoxifen does not indicate increased risk of recurrence. Evidence on red clover is limited, however existing studies suggest that it may not possess breast cancer-promoting effects.<h4>Conclusion</h4>Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does not have estrogenic effects in humans. Soy intake consistent with a traditional Japanese diet appears safe for breast cancer survivors. While there is no clear evidence of harm, better evidence confirming safety is required before use of high dose (≥ 100 mg) isoflavones can be recommended for breast cancer patients.
Project description:Individuals with obesity and metabolic syndrome (MetS) are at increased risk of cardiovascular disease, in part due to heightened inflammatory/oxidative processes. Results from epidemiologic and experimental studies suggest that citrus, and grapefruit in particular, may have a role in promoting vascular health, although clinical trial data are lacking. Here, we evaluated the anti-inflammatory/antioxidant effects of habitual grapefruit consumption in 69 overweight/obese men and women and in a subsample of participants with MetS (n = 29). Participants were randomly assigned to either a grapefruit group in which they consumed a low bioactive diet plus 1.5 grapefruit/d for 6 wk (n = 37, n = 14 with MetS) or to a control condition in which a low bioactive diet devoid of citrus was consumed (n = 32, n = 15 with MetS). Plasma soluble vascular adhesion molecule-1 (sVCAM-1), plasma high-sensitivity C-reactive protein (hsCRP), and urinary F2-isoprostanes were evaluated before and after the intervention phase. F2-isoprostane concentrations were not different in the grapefruit versus control arm after the intervention (12.4 ± 6.4 vs. 15.9 ± 9.0 ng/mg creatinine, P = 0.16), whereas plasma hsCRP concentrations tended to be lower in the grapefruit versus control arm postintervention (2.1 ± 1.5 vs. 2.8 ± 2.0 mg/L, P = 0.09). In adults with MetS, grapefruit consumption tended to result in lower postintervention F2-isoprostane concentrations compared with the control condition (12.0 ± 4.5 vs. 18.3 ± 10.9 ng/mg creatinine, P = 0.06). Furthermore, those with high baseline F2-isoprostane concentrations experienced significant reductions in this biomarker in response to grapefruit consumption (P = 0.021). Change in sVCAM-1 concentrations did not vary by treatment arm nor were there differences between arms postintervention. These results suggest that intake of grapefruit twice daily for 6 wk does not significantly reduce inflammation and oxidative stress, although there is a suggestion of favorable modulation of oxidative stress in overweight and obese adults with MetS or those with high baseline urine F2-isoprostane concentrations.
Project description:On the basis of hypothesized protective effect, we examined the effect of soy foods on estrogens in nipple aspirate fluid (NAF) and serum, possible indicators of breast cancer risk.In a crossover design, we randomized 96 women who produced 10 ?L or more NAF to a high- or low-soy diet for 6 months. During the high-soy diet, participants consumed 2 soy servings of soy milk, tofu, or soy nuts (?50 mg of isoflavones per day); during the low-soy diet, they maintained their usual diet. Six NAF samples were obtained using a FirstCyte aspirator. Estradiol (E(2)) and estrone sulfate (E(1)S) were assessed in NAF and estrone (E(1)) in serum only, using highly sensitive radioimmunoassays. Mixed-effects regression models accounting for repeated measures and left-censoring limits were applied.Mean E(2) and E(1)S were lower during the high-soy than the low-soy diet (113 vs. 313 pg/mL and 46 vs. 68 ng/mL, respectively) without reaching significance (P = 0.07); the interaction between group and diet was not significant. There was no effect of the soy treatment on serum levels of E(2) (P = 0.76), E(1) (P = 0.86), or E(1)S (P = 0.56). Within individuals, NAF and serum levels of E(2) (r(s) = 0.37; P < 0.001) but not of E(1)S (r(s) = 0.004; P = 0.97) were correlated. E(2) and E(1)S in NAF and serum were strongly associated (r(s) = 0.78 and r(s) = 0.48; P < 0.001).Soy foods in amounts consumed by Asians did not significantly modify estrogen levels in NAF and serum.The trend toward lower estrogen levels in NAF during the high-soy diet counters concerns about adverse effects of soy foods on breast cancer risk.
Project description:The purpose of this 3-way crossover study was to identify the effective dose of soy protein isolate enriched with isoflavones for suppressing bone resorption in postmenopausal women using a novel, rapid assessment of antibone resorbing treatments.Thirteen postmenopausal women (>or=6 yr since menopause) were predosed with 41Ca iv. After a 200-d baseline period, subjects were given 43 g soy protein/d that contained 0, 97.5, or 135.5 mg total isoflavones in randomized order. The soy protein isolate powder was incorporated into baked products and beverages. Each 50-d intervention phase was preceded by a 50-d pretreatment phase for comparison. Serum isoflavone levels and biochemical markers were measured at the end of each phase. Twenty-four-hour urine samples were collected approximately every 10 d during each phase for 41Ca/Ca analysis by accelerator mass spectrometry.Serum isoflavone levels reflected the amount of isoflavones consumed in a dose-dependent manner. None of the isoflavone levels had a significant effect on biochemical markers of bone turnover, urinary cross-linked N teleopeptides of type I collagen and serum osteocalcin, or bone turnover as assessed by urinary 41Ca/Ca ratios.Soy protein with isoflavone doses of up to 135.5 mg/d did not suppress bone resorption in postmenopausal women. This is the first efficacy trial using the novel technique of urinary 41Ca excretion from prelabeled bone.