Urinary Excretion Of Daidzein Research Articles

Soy isoflavones interact with calcium and contribute to blood pressure homeostasis in women: a randomized, double-blind, placebo controlled trial.

Estrogens and calcium regulate vascular health but caused adverse cardiovascular events in randomized trials. Whether phytoestrogenic soy isoflavones modulate the physiological effects of calcium on blood pressure was explored. A double-blind, randomized study assigned 99 premenopausal women to 136.6mg isoflavones (as aglycone equivalents) and 98 to placebo for 5days per week for up to 2years. Blood pressure, serum calcium and urinary excretion of daidzein (DE) and genistein (GE) were measured repeatedly before and during treatment. Isoflavones did not affect blood pressure per intake dose assignment (i.e. intention-to-treat, n = 197), but significantly affected blood pressure per measured urinary excretion of isoflavones (i.e. per protocol analysis, n = 166). Isoflavones inversely moderated calcium effects on systolic blood pressure (SBP) (interaction term β-estimates: - 3.1 for DE, - 12.86 for GE, all P < 0.05), and decreased diastolic blood pressure (DBP) (β-estimates: - 0.84 for DE, - 2.82 for GE, all P < 0.05) after controlling for calcium. The net intervention effects between the maximum and no isoflavone excretion were - 17.7 and + 13.8mmHg changes of SBP, respectively, at serum calcium of 10.61 and 8.0mg/dL, and about 2.6mmHg decrease of DBP. Moderation by isoflavones of the physiological effect of calcium tends to normalize SBP, and this effect is most significant when calcium concentrations are at the upper and lower limits of the physiological norm. Isoflavones decrease DBP independent of calcium levels. Further studies are needed to assess the impact of this novel micronutrient effect on blood pressure homeostasis and cardiovascular health. www.clinicaltrials.gov identifier: NCT00204490.

Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: A 2-year randomized, double-blind, placebo-controlled study

Soy isoflavones are potentially beneficial phytoestrogens, but their tissue-selective effects in women are poorly understood. We tested the hypothesis that soy isoflavones affect bone mineral density (BMD), which may be influenced by individual differences in isoflavone metabolism and serum calcium levels. Ninety-nine healthy premenopausal women were randomized to isoflavones (136.6 mg aglycone equivalence) and 98 to placebo for 5 days per week for up to 2 years. BMD, serum calcium, and urinary excretion of daidzein and genistein were measured before and during treatment. In 129 adherent subjects, we found that isoflavone exposure, determined by urinary excretion levels, but not by dose assignment, interacted with serum calcium in affecting whole body BMD, but not hip and spine BMD. The regression coefficient was −0.042 for genistein excretion (GE) and 0.091 for the interaction between GE and serum calcium (all P < .05). Daidzein excretion had similar but marginal effect. Genistein significantly decreased whole body BMD only at low normal serum calcium levels but increased whole body BMD at higher serum calcium levels. Comparing maximum to minimum GE, mean changes in whole body BMD were +0.033 and −0.113 g/cm2 at serum calcium levels of 10 and 8.15 mg/dL, respectively. These associations were not evident by intention-to-treat analysis, which could not model for inter-individual differences in isoflavone metabolism. In summary, soy isoflavones decrease whole body BMD only when serum calcium is low. Isoflavones are dietary substances that may influence calcium homeostasis by releasing calcium from bone while sparing the common fracture risk sites hip and spine.

Inter- and intra-individual variation in urinary excretion of daidzein and equol in female Japanese

Objective: To evaluate the representativeness of single measurement of urinary soy-isoflavone concentrations for the assessment of long-term intake levels.Methods: Five urine samples taken from 14 Japanese female subjects over 2–3 months were measured for daidzein and equol by gas chromatography-mass spectrometry (GC-MS).Results: Geometric mean daidzein and equol concentrations of 14 subjects were 582 and 2.66 μg/g creatinine, respectively. Intra-class correlation coefficients for daidzein and equol were 0.355 (95% CI: 0.130–0.649) and 0.741 (0.551–0.891), respectively.Conclusion: Single measurement of urinary equol is effective for the assessment of long-term equol status of Japanese subject while that of daidzein is not.

Lesser in vitro anaerobic cecal isoflavone disappearance was associated with greater apparent absorption of daidzein and genistein in Golden Syrian hamsters

Our hypothesis in this study was that in vitro disappearance of isoflavones from fecal or cecal contents of Golden Syrian hamsters paralleled the apparent absorption of these compounds, comparable with previous findings from in vitro human fecal incubations. Two studies were conducted to test this idea: one on in vitro fecal (study 1, n = 20/sex) and the other on in vitro cecal contents (study 2, n = 10/sex) ability to degrade isoflavones. According to HPLC analysis, urinary isoflavone excretion was significantly less by 2-4 fold in males compared with females in both studies. Fecal isoflavone excretion was not significantly different between sexes or isoflavones (study 1) and was <0.5% of ingested dose. In vitro anaerobic fecal isoflavone degradation rate constants from study 1 were minimal with no significant correlation between urinary and fecal isoflavone excretion. However, in vitro anaerobic cecal isoflavone degradation rate constants (study 2) were greater and significantly correlated with urinary excretion of daidzein (R = 0.90; p = 0.01) and genistein (R = 0.93; p = 0.004), but not glycitein (R = 0.50; p = 0.3). Both male and female hamsters showed a pattern of urinary isoflavone excretion similar to that found in humans (daidzein > genistein). Hamster in vitro cecal isoflavone degradation rate constants seemed to be analogous to human in vitro fecal isoflavone degradation rate constants for genistein and daidzein. The sex difference in isoflavone excretion in hamsters and the instability in glycitein excretion across studies coupled with the paucity of human data on this isoflavone deserve further investigation.

Urinary phytoestrogen excretion and prostate cancer risk: a nested case–control study in the Multiethnic Cohort

Background:Phytoestrogens are of special interest in prostate cancer research because populations in Asia with a high consumption of phytoestrogens have a lower incidence of the disease than comparable populations in Western countries.Methods:This case–control study is nested within a large multiethnic cohort in Hawaii and California. Urine samples were analysed for daidzein, genistein, equol, and enterolactone among 249 incident prostate cancer cases and 404 controls matched on age, race/ethnicity, date/time of specimen collection, and fasting status.Results:The median excretion of daidzein was 0.173 nmol mg−1 creatinine in cases and 0.291 in controls (P=0.01), and the median excretion of genistein was 0.048 in cases and 0.078 in controls (P=0.05). An inverse association was seen for daidzein overall (odds ratio for the highest vs lowest quintile=0.55, 95% confidence interval=0.31–0.98, Ptrend=0.03) and seemed to apply to localized (Ptrend=0.08) as well as advanced or high-grade cancer (Ptrend=0.09). This association was consistent across the four ethnic groups examined. Although the relationship was weaker for genistein, the odds ratios and trends were similarly inverse. Urinary excretion of equol and enterolactone was not significantly related to prostate cancer risk.Conclusion:Our findings suggest that high intake of isoflavones, as reflected by urinary excretion of daidzein and genistein, may be protective against prostate cancer.

Urinary phytoestrogen excretion and prostate cancer risk in a nested case‐control study: The Multiethnic Cohort

Phytoestrogens are of special interest in prostate cancer research because populations in Asia with a high consumption of phytoestrogens have a lower incidence of the disease than comparable populations in Western countries. This case‐control study is nested within a multiethnic cohort in Hawaii and California. Analyses included 249 incidence prostate cancer cases and 404 matched controls for urinary daidzein, genistein, equol, and enterolactone. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) to account for the matching criteria as well as adjusted for covariates. The median excretion of daidzein was 0.173 nmol/mg creatinine in cases and 0.291 in controls (p = 0.01), and the median excretion of genistein was 0.048 in cases and 0.078 in controls (p = 0.05). An inverse association was seen for daidzein overall (OR for the highest vs. lowest quintile = 0.55, 95% CI = 0.31‐0.98, p for trend = 0.03) and for localized as well as advanced or high grade cancer and was suggested for each of the four ethnic groups examined. Urinary excretion of genistein, equol, and enterolactone was not significantly related to prostate cancer risk. Our findings suggest that high intake of phytoestrogens, as reflected by urinary excretion of daidzein, may be protective against prostate cancer. Grant support: P01 CA33619 and R37 CA54281.

Validation of soy protein estimates from a food-frequency questionnaire with repeated 24-h recalls and isoflavonoid excretion in overnight urine in a Western population with a wide range of soy intakes

BackgroundEvidence of the benefits of soy on cancer risk in Western populations is inconsistent, in part because of the low intake of soy in these groups. ObjectiveWe assessed the validity of soy protein estimates from food-frequency questionnaires (FFQs) in a sample of Adventist Health Study-2 participants with a wide range of soy intakes. DesignWe obtained dietary intake data from 100 men and women (43 blacks and 57 nonblacks). Soy protein estimates from FFQs were compared against repeated 24-h recalls and urinary excretion of daidzein, genistein, total isoflavonoids (TIFLs), and equol (measured by HPLC/photodiode array/mass spectrometry) as reference criteria. We calculated Pearson and Spearman correlation coefficients (with 95% CIs) for FFQ–24-h recall, 24 h-recall–urinary excretion, and FFQ–urinary excretion pairs. ResultsAmong soy users, mean (± SD) soy protein values were 12.12 ± 10.80 g/d from 24-h recalls and 9.43 ± 7.83 g/d from FFQs. The unattenuated correlation (95% CI) between soy protein estimates from 24-h recalls and FFQs was 0.57 (0.32, 0.75). Correlation coefficients between soy protein intake from 24-h recalls and urinary isoflavonoids were 0.72 (0.43, 0.96) for daidzein, 0.67 (0.43, 0.91) for genistein, and 0.72 (0.47, 0.98) for TIFLs. Between FFQs and urinary excretion, these were 0.50 (0.32, 0.65), 0.48 (0.29, 0.61), and 0.50 (0.32, 0.64) for daidzein, genistein, and TIFLs, respectively. ConclusionsSoy protein estimates from questionnaire were significantly correlated with soy protein from 24-h recalls and urinary excretion of daidzein, genistein, and TIFLs. The Adventist Health Study-2 FFQ is a valid instrument for assessing soy protein in a population with a wide range of soy intakes.

Age-Related Uterotrophic Response of Soy Isoflavone Intake in Rats

This study investigated the effects of soy isoflavone intake on uterotrophic responses in growing (juvenile) and adult female rats. In the growing rats, feed intake showed a decreasing trend as the level of dietary isoflavones increased to 0.02%, 0.1%, and 0.2% of the diets. However, in the case of the adult rats there were no significant differences among groups. Weight gains were significantly lower in the rats fed 0.1% and 0.2% isoflavones than the controls in both juvenile and adult rats. The urinary excretion of daidzein and genistein was significantly increased with increasing levels of dietary isoflavones. The calculated urinary recoveries of daidzein and genistein were significantly lower in the groups fed 0.1% and 0.2% isoflavones compared to the juvenile and adult rat groups fed 0.02% isoflavones; no significant difference was observed between the 0.1% and 0.2% groups. The calculated urinary recoveries of daidzein and genistein in the adult rats were significantly higher than in the juvenile rats. The differences in the urinary recoveries between ages may be due to greater availability of the isoflavones in the adult rats. Isoflavone supplementation did not alter the histological phenotype of endometrial cells in growing rats, but a hyperplastic response of endometrium was shown in the adult rats. Dietary isoflavones, therefore, may not have an estrogenic effect on the uterus at these dose levels during the growth period, but this organ would be expected to be a likely target for isoflavone action in adults. We observed in the present study that isoflavones are more bioavailable in adult rats than in the juvenile rats. Therefore, soy isoflavone supplementation may not act as an endocrine disrupter during the growth period but may exert a phytoestrogenic effect on the uterus of adult rats.

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

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. A total of 12 Caucasian postmenopausal women. 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. 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. 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.

Daidzein conjugates are more bioavailable than genistein conjugates in rats

This study compared the bioavailability of conjugates of the soy isoflavones genistein and daidzein in rats. Rats were given a single oral dose of a soy extract that provided 74 μmol genistein and 77 μmol daidzein/kg body wt (as conjugates). Plasma samples were obtained from treated and untreated rats; urine and fecal samples were obtained before and after treatment. Isoflavones, equol (the main end product of bacterial degradation of daidzein), and 4-ethyl phenol (the main end product from genistein) were measured by HPLC. The plasma daidzein concentration was maximal at 2 h (9.5 ± 0.71 μmol/L) and was almost double that of genistein (P = 0.009). Between 2 and 15 h, the plasma daidzein concentration declined by 32%, but the concentration of genistein changed little. At 15 h, the concentrations of daidzein and genistein were not significantly different. Urinary excretion of daidzein over the 48- h postdose period was 17.4 ± 1.2% of the dose, but only 11.9 ± 1.1% of the genistein dose was excreted in urine. Equol excretion was 5.0 ± 1.5% of the daidzein dose, but 41.9 ± 5.0% of the genistein dose was excreted as 4-ethyl phenol. Fecal daidzein accounted for 2.3 ± 0.5% and fecal genistein for 3.4 ± 0.4% of the respective doses. It is concluded that conjugates of daidzein are more bioavailable than those of genistein, probably because of the greater resistance of the former to degradation by gut bacteria.