Equol Production Research Articles

Daidzein-metabolizing phenotypes in relation to serum hormones and sex hormone binding globulin, and urinary estrogen metabolites in premenopausal women in the United States

Blood and urine concentrations of hormones are implicated in the etiology of some cancers. Small studies have assessed relationships between production of the daidzein metabolites equol and O-desmethylangolensin (ODMA) and hormones, but findings are unclear. We evaluated relationships between daidzein-metabolizing phenotypes and follicular phase concentrations of estrogens, androgens, sex hormone binding globulin (SHBG), and urinary estrogen metabolites in premenopausal women. Two-hundred women collected a first-void urine sample after a 3-day soy challenge, and 191 and 193 provided fasting blood and spot urine samples, respectively, during days 5-9 of their menstrual cycle. Soy challenge urines were analyzed for isoflavones; serum was analyzed for estrogens, androgens, and SHBG; spot urines were analyzed for 2-hydroxyestrone and 16alpha-hydroxyestrone. Data were log-transformed and multiple regression analyses were conducted to assess relationships between daidzein-metabolizing phenotypes and hormones and SHBG. Data from 187 and 189 women were included in analyses of serum and urine hormones, respectively. 55 (27.5%) and 182 (91%) of the 200 women who provided a soy challenge urine sample were equol- and ODMA-producers (>87.5 ng/ml urine), respectively. In unadjusted analyses, equol-producers (n = 52) had lower free testosterone than equol non-producers (n = 137, p = 0.02). In adjusted analyses, there were no differences between producers and non-producers of either daidzein metabolite. In the absence of a soy intervention, we found no difference in serum or urine hormone concentrations between producers and non-producers of equol or ODMA.

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.

Biotransformation of soy isoflavones and enhanced cholesterol lowering effect with an oligofructose‐enriched inulin in equol producers

Objective: To assess whether the hypocholesterolemic effect of soy can be enhanced with an oligofructose‐enriched inulin (OF‐IN) by promoting the biotransformation of colonic soy isoflavones (i.e. equol production). Method: 23 hyperlipidemic adults (11M, 12F; 58±7y; LDL‐C, 4. 1±0.7mmol/L) completed three 4‐week phases: OF‐IN (10 g/d) and low‐fat dairy (control), and soy foods (isoflavones, 61 mg/d) with or without OF‐IN (10 g/d). Fasting blood lipids and anthropometrics were measured biweekly. Urine (24h) was collected at baseline and at the end of each phase. Results: A stepwise reduction in TChol:HDL‐C was observed for OF‐IN (0.25±0.13, P=0.08), soy (–0.07±0.08, P=0.41) and soy plus OF‐IN (–0.36±0.14, P=0.02), compared to baseline. Preliminary analysis suggested that this effect was seen most clearly in equol producers (n=7). TChol:HDL‐C for equol producers was 0.09±0.16 on OF‐IN, –0.23±0.14 on soy, and –0.72±0.42 on soy plus OF‐IN, compared to baseline. For non‐equol producers, TChol:HDL‐C was 0.41±0.17, 0.04±0.09, and –0.17±0.08, respectively. Conclusion: Intake of soy in conjunction with OF‐IN resulted in greater improvements in the lipid profile than their intake alone, suggesting a synergistic effect. This association was more prominent in equol producers possibly related to increased biotransformation of soy isoflavones.Funding: Heart and Stroke Foundation of Ontario, ORAFTI Group

The Effect of Soy Supplementation on Human Gut Microflora Community in Post‐Menopausal Women

Soy isoflavones and their metabolites can mimic estrogen and thus, may carry health benefits for postmenopausal women as alternatives to hormone replacement therapy. Equol, a metabolite of daidzein, is suggested to be more beneficial, but to date, the bacteria responsible for this conversion have not been identified conclusively. This research was aimed at characterizing changes in the gastrointestinal microflora of post‐menopausal women with the addition of a soy bar to their diet and therein to identify organisms that might be responsible for equol production. Bacterial DNA was extracted from fecal samples collected from 6 women for 14 consecutive days, with women consuming one soy bar/d (160 mg of isoflavones) from day 8–11. Fingerprints of 16S rRNA of the microbial community for the 14‐day study period were generated using PCR‐DGGE. Results indicated that all subjects had stable microbial fingerprint profiles and there appeared to be no clear effect of soy. In contrast, analyses based on bifidobacterial‐specific primers indicated an increase in Bifidobacteria as a function of soy, in most subjects. Also, equol producers had a more diverse bifidobacterial community, even in the absence of soy. Future work will focus on characterizing members of the bifidiobacterial community qualitatively and quantitatively, and determine for the presence of organisms that have been associated with equol production.

Demographic, anthropometric, and lifestyle factors and dietary intakes in relation to daidzein-metabolizing phenotypes among premenopausal women in the United States

Background: The soy isoflavone daidzein is metabolized to equol and O-desmethylangolensin (ODMA) by intestinal bacteria in ≈30–50% and 80–90% of persons, respectively. Studies suggest beneficial health effects associated with daidzein-metabolizing phenotypes; thus, assessing their determinants is an important goal.Objective: We evaluated relations between daidzein-metabolizing phenotypes and demographic, anthropometric, lifestyle, and dietary factors among premenopausal women in the United States.Design: Two hundred women provided a first-void urine sample after a 3-d soy challenge and completed a health and demographics questionnaire, physical activity questionnaire, food-frequency questionnaire, and 3-d food record. Urine samples were measured for isoflavones by gas chromatography–mass spectrometry to determine daidzein-metabolizing phenotypes.Results: Fifty-five (27.5%) and 182 (91%) women had detectable concentrations of urinary equol and ODMA (>87.5 ng/mL), respectively, and were classed as producers of these metabolites. Compared with nonproducers, equol producers were more likely (P ≤ 0.05) to be Hispanic or Latino, to be highly educated, and to have frequent constipation, and ODMA producers were taller and less likely to be Asian than white. Equol and ODMA producers reported higher overall physical activity than did nonproducers.Conclusions: We observed associations between equol production and ethnicity, education, constipation, and physical activity and between ODMA production and race, height, and physical activity. Associations with race and ethnicity were based on small numbers of Asian and Hispanic or Latino women, and confirmation of these findings is needed. Few dietary factors, assessed with the use of either a food-frequency questionnaire or food record, were associated with daidzein-metabolizing phenotypes.

Low activities of intestinal lactase suppress the early phase absorption of soy isoflavones in Japanese adults

The contribution of lactase to isoflavone bioavailability has not been clarified. We evaluated the association between lactase activity and the bioavailability of isoflavone glucosides in Japanese adults. Twenty-six Japanese adult participants completed a study that included tests of breath hydrogen after a lactose load, orocecal transit time, and isoflavone glucoside absorption. Lactose malabsorbers were defined as those with an increase in breath hydrogen level (DeltaH(2)) of more than 20 ppm after a load of lactose (20 g). Participants ingested 200 ml soymilk, and serum isoflavones were analyzed until 480 min. Serum daidzein and genistein levels increased rapidly until 60 min, then slowly increased. The increases of serum isoflavones in the early phase, but not the later phase, were suppressed in lactose malabsorbers. DeltaH(2 max) after a load of lactose inversely correlated with serum daidzein levels at 30 min. The percentage of equol producers tended to be greater among lactose malabsorbers (P=0.067). Lactase may be involved in absorption of isoflavone glucosides in the small intestine, but the bacterial deglycosylation in the large intestine compensates the reduction of isoflavone absorption. The beneficial effect of isoflavones may not be impaired by low lactase activity.

Age-stratified serum levels of isoflavones and proportion of equol producers in Japanese and Korean healthy men

Racial differences in the incidence of prostate cancer are manifest worldwide, possibly due to the different dietary habits. To elucidate the relationship between the recent trend of phytoestrogenic isoflavone intake and the increased incidence of prostate cancer in Japan, we conducted an age-stratified dietary survey of soybean foods in 102 Japanese healthy men (age range: 10-59 years) and measured the serum isoflavones and equol levels in them and 100 Korean healthy men. The intergroup comparison among the age-stratified groups showed significant differences in the daily intake of genistein and daidzein between the teenager group and the other groups of age >or=30 years (P<0.05). In the Japanese study, the proportion of equol producers in the teenager group was 10%, being significantly the lowest among the age-stratified groups. The proportions of equol producers in the age-stratified groups from 10 to 49 years were also significantly lower than those in the fifties. The equol non-producers consumed significantly less amounts of isoflavones than the equol producers. In the Korean study, the proportions of equol producers were 45% in the teenager and 40% in the twenties and thirties, being significantly lower than in the forties (80%) and fifties (65%). The decreased intake of isoflavones, low serum level of equol and low incidence of equol production in the young generation may become potential risk factors for prostate cancer not only in Japan but also in Korea in the near future. Elucidating the mechanism of equol production may be promising in developing strategies for chemoprevention against prostate cancer.

Impact of soy supplementation on sex steroids and vascular inflammation markers in postmenopausal women using tibolone: role of equol production capability

Objectives Tibolone is often taken concurrently with soy. Tibolone, soy and equol-producing capacity each affect vascular health, whereas their concomitant effects are unknown. We studied the effects of soy on sex steroids and vascular inflammation markers in long-term tibolone users.Methods Postmenopausal women (n = 110) on tibolone were screened with a soy challenge to find 20 equol producers and 20 non-producers. All women were treated for 8 weeks in a cross-over trial with soy (52 g of soy protein containing 112 mg of isoflavones) or placebo. Serum estrone, 17β-estradiol, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and platelet-selectin (P-selectin) were assessed.Results Soy decreased (7.1%) the estrone level, significantly (12.5%) only in equol producers (from 80.2 ± 10.8 to 70.3 ± 7.0 pmol/l; p = 0.04). Testosterone was reduced (15.5%; from 586 ± 62.6 to 495 ± 50.1 pmol/l, p = 0.02) during soy treatment, and more markedly in equol producers than non-producers (22.1% vs. 10.0%). No changes appeared in SHBG, CRP or ICAM-1, but VCAM-1 increased (9.2%) and P-selectin decreased (10.3%) during soy treatment.Conclusions Soy modified the concentrations of estrone, testosterone and some endothelial markers. Equol production enforced these effects. Soy supplementation may be clinically significant in tibolone users.

Equol Status Modifies the Association of Soy Intake and Mammographic Density in a Sample of Postmenopausal Women

Only 30% to 50% of people produce the daidzein-metabolite equol after eating soy. We conducted a cross-sectional study of the associations between equol status, intake of soy foods, and mammographic density in a sample of postmenopausal women recruited at a radiology clinic near Buffalo, New York. Participants were 48 to 82 years old, had no history of cancer or breast reduction/augmentation, and no recent use of antibiotics or hormones. Percent density was measured by computer-assisted analysis of digitized images of craniocaudal films. Equol status was assessed using a soy-challenge protocol and usual soy intake by questionnaire. General linear models were used to assess independent and joint effects of equol status and intake of soy on multivariate adjusted percent density (covariates included age, body mass index, parity, age at first birth, and ever use of combined hormone therapy). Of 325 enrolled, 232 (71%) participants completed study assessments and are included in the present analysis. Mean percent density was 34% (+/-18%). Seventy-five (30%) participants were producers of equol. Forty-three (19%) participants reported regularly eating >1 soy food or supplement/wk. There were no significant independent associations of equol status or soy intake with percent density, but the interaction between these factors was significant (P < 0.01). Among equol producers, those with weekly soy intake had lower percent density (30.7% in weekly consumers of soy versus 38.9% in others; P = 0.08); among nonproducers, weekly soy intake was associated with higher percent density (37.5% in weekly soy consumers versus 30.7% in others; P = 0.03). Results suggest that equol producers and nonproducers may experience different effects of dietary soy on breast tissue.

Dose-response assessment of the anti-cancer efficacy of soy isoflavones in dimethylhydrazine-treated rats fed 6% fructooligosaccharide

We investigated the combinatorial effects of different doses of dietary soy isoflavones (SI) and fructooligosaccharide (FOS) in a rat model of colon cancer. We hypothesized that increased bioavailability of SI metabolites due to dietary FOS may increase production of bioactive equol and affect colon carcinogenesis in a dose-dependent manner. Sprague-Dawley male rats were injected with 12-dimethylhydrazine (DMH) and were provided experimental diets that contained 0, 10, 50, 150, or 500 mg SI per kg of diet and 6% FOS for 12 weeks. The number of aberrant crypt foci (ACF) and the expression of cyclooxygenase-2 (COX-2) in colonic tissues were significantly decreased in the 6% FOS-fed groups compared to the control group. Gut transit time and fecal pH were significantly lower, and fecal concentrations of bifidobacteria were increased with 6% FOS. However, dietary SI supplementation in combination with 6% dietary FOS did not affect ACF formation or COX-2 expression. Plasma equol concentrations were dose-dependently increased by supplementation of SI up to 500 mg/kg of diet. In conclusion, SI supplementation up to 500 mg/kg of diet appeared to have no additive beneficial effects in rats with chemically-induced colon cancer that were fed 6% FOS, although plasma equol was dose-dependently increased.

Dietary and Lifestyle Correlates of Urinary Excretion Status of Equol in Japanese Women

The isoflavone metabolite equol has been identified in urine or blood samples in some but not all humans. In this cross-sectional study, we examined the association between lifestyle, including diet, and the urinary excretion of equol. Study subjects were 419 Japanese women who were recruited from a breast cancer screening center. Each woman responded to a self-administered questionnaire seeking information about health and lifestyle factors. Diet was assessed by a validated semiquantitative food frequency questionnaire. Urinary isoflavones were measured using spot urine samples. Equol was detected in the urine of 84 (20.0%) women. After controlling for covariates, it was found that dairy product intake was significantly lower in those who excreted detectable equol levels in urine than in those who did not. Because equol is derived from daidzein, individuals with low intake of daidzein may produce undetectable levels of equol. To account for this, the study subjects were restricted to 163 women with urinary daidzein levels of 10 nmol/mg creatinine or higher. The association of equol excretion with dairy product intake remained significant. Demographic factors, smoking status, and menstrual and reproductive factors were unrelated to equol excretion. These data suggest that dairy product intake may be associated with the production of equol.

Equol production capability is associated with favorable vascular function in postmenopausal women using tibolone; no effect with soy supplementation

Objective Equol, a gut bacterial metabolite of isoflavone daidzein, may improve health through changes in vascular function and in estrogen metabolism. Tibolone, a synthetic steroid alternative for the treatment of postmenopausal symptoms, causes a different estrogenic milieu than estrogen and may affect vascular health. We studied the effects of equol production and soy supplementation on vascular function in postmenopausal women under long-term tibolone use. Methods We screened 110 women using tibolone for 3–60 months for high equol production capacity with a one-week soy challenge. Twenty women with high equol production capacity (4-fold elevation in equol level) and 20 comparable control women without this capacity were treated in a randomized placebo-controlled cross-over trial with a soy drink (52 g of soy protein containing 112 mg of isoflavones) or placebo for 8 weeks. Arterial stiffness and endothelial function were assessed before and after soy and placebo supplementation with pulse-wave analysis. Results Prior to soy supplementation arterial stiffness, expressed as augmentation index, was lower ( p = 0.01) in equol producers (25.9 ± 1.1%) than non-equol producers (29.6 ± 0.9%). Similarly, endothelial function index was better at baseline ( p = 0.009) in these women (72.3 ± 5.3%) compared to women lacking equol production capacity (55.2 ± 3.8%). Soy supplementation had no effect on arterial stiffness or endothelial function in either group. Conclusion In postmenopausal tibolone users, endogenous equol production capability is associated with favorable vascular function. This phenomenon was not affected by soy and thus, equol producing capacity may be an independent vascular health marker, at least in postmenopausal women using tibolone.

Microbial and Dietary Factors Are Associated with the Equol Producer Phenotype in Healthy Postmenopausal Women , ,3

Equol, a microbial metabolite of daidzein, has been hypothesized as a clue to the effectiveness of soy and its isoflavones but is excreted by only 33% of Caucasians. Microbial and dietary factors associated with the ability to harbor equol-producing bacteria were studied in a randomized dietary intervention trial with 100 healthy postmenopausal women. After a 4-d baseline period, subjects delivered first-void urine, fecal, and breath samples. During the 5-d treatment period, 3 portions of either soymilk or soy germ containing 28.51 and 37.99 mg isoflavone aglycone equivalents/portion, respectively, were administered daily, and on the last day, 24-h urine samples were collected. The urinary recoveries of genistein and daidzein from soymilk were significantly higher than those from soy germ tablets. Because the proportion of equol:(daidzein + metabolites) in the urine did not differ between the treatment groups, subjects were pooled and classified into poor, moderate, and strong equol producers based on this criterion. The strong equol producer phenotype correlated negatively [in vivo, r = −0.478 (−0.256 to −0.893), P = 0.021; in vitro, r = −0.576 (−0.350 to −0.949), P = 0.030] with Clostridium coccoides-Eubacterium rectale counts and positively [in vivo, r = 1.158 (0.971–1.380), P = 0.048; in vitro, r = 1.156 (1.007–1.327), P = 0.039] with the abundance of sulfate-reducing bacteria. Furthermore, persons with a higher PUFA [in vivo, r = 2.150 (1.058–4.371), P = 0.034; in vitro, r = 2.131 (1.144–3.967), P = 0.017] and alcohol [in vivo, r = 1.166 (0.721–1.887), P = 0.050; in vitro, r = 1.850 (1.215–2.817), P = 0.004] intake were more likely to be strong equol producers. Finally, we validated the daidzein metabolism by fecal cultures as screening assay to identify equol producers without dietary intervention.

Pasta Naturally Enriched with Isoflavone Aglycons from Soy Germ Reduces Serum Lipids and Improves Markers of Cardiovascular Risk

Most studies of soy and cholesterol have tested foods made from purified soy proteins containing mainly isoflavone glycosides. Fermented soy foods have mainly isoflavone aglycons and account for a high proportion of the soy protein source in Asia, where there is an inverse relationship between soy intake and serum cholesterol. The aim of this study was to compare a novel soy germ pasta, naturally enriched in isoflavone aglycons as a result of the manufacturing process, with conventional pasta for effects on serum lipids and other cardiovascular risk markers. In this randomized, controlled, parallel study design of 62 adults with hypercholesterolemia who consumed a Step II diet that included one 80-g serving/d of pasta, we measured serum lipids, high sensitivity C-reactive protein (hsCRP), urinary isoprostanes, and brachial artery flow-mediated vasodilatation at baseline and after 4 and 8 wk. The pasta delivered 33 mg of isoflavones and negligible soy protein and led to a serum isoflavone concentration of 222 ± 21 nmol/L; 69% of subjects were equol producers. Soy germ pasta reduced serum total and LDL cholesterol by 0.47 ± 0.13 mmol/L (P = 0.001) and 0.36 ± 0.10 mmol/L (P = 0.002) more than conventional pasta, representing reductions from baseline of 7.3% (P = 0.001) and 8.6% (P = 0.002), respectively. Arterial stiffness (P = 0.003) and hsCRP (P = 0.03) decreased and improvements in all the above risk markers were greatest in equol producers. All measures returned to baseline when patients were switched to conventional pasta. In conclusion, pasta naturally enriched with isoflavone aglycons and lacking soy protein had a significant hypocholesterolemic effect beyond a Step II diet and improved other cardiovascular risk markers.

Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women

To investigate the effect of soy protein containing isoflavones on homocysteine (Hcy), C-reactive protein (CRP), soluble E-selectin (sE-selectin), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1). In a randomized crossover design, 34 postmenopausal women consumed soy protein isolate (26+/-5 g protein containing 44+/-8 mg isoflavones per day) or milk protein isolate (26+/-5 g protein per day) for 6 weeks each. Fasting blood samples were collected at the end of each diet period and end points analyzed by enzyme-linked immunosorbent assay. Concentrations of Hcy, CRP, sE-selectin, sVCAM-1 and sICAM-1 were not different between soy and milk diet treatments. Results did not differ by equol production status or by baseline lipid concentration. Adjustment for intake of folate and methionine did not alter the Hcy results. These data suggest that decreasing vascular inflammation and Hcy concentration are not likely mechanisms by which soy consumption reduces coronary heart disease risk.

Possible role of equol status in the effects of isoflavone on bone and fat mass in postmenopausal Japanese women

Equol is more biologically active than its precursor daidzein, which is the principal isoflavone found in soybean. There are interindividual differences in the ability to produce equol; these may lead to differences in the effects of isoflavone intervention on human health. This study aimed to investigate whether the effects of soy isoflavones on bone and fat mass are related to an individual's equol status. We performed a 1-year double-blind, randomized trial to compare the effects of isoflavone (75 mg of isoflavone conjugates/day) with those of placebo on bone mineral density, fat mass, and serum isoflavone concentrations in early postmenopausal Japanese women who were classified based on their equol-producer phenotype. After 1 year, the isoflavone intervention significantly increased the serum equol concentration in the equol producers but not in the nonproducers. In the isoflavone group, the annualized changes in the bone mineral density of the total hip and intertrochanteric regions were -0.46% and -0.04%, respectively, in the equol producers and -2.28% and -2.61%, respectively, in the nonproducers; these values were significantly different (P<0.05 for both the regions). Significant differences were observed between the equol producers and nonproducers in the isoflavone group with regard to the annualized changes in the fat mass. No significant difference in the annualized changes in bone mineral density and fat mass was observed between the equol producers and nonproducers in the placebo group. Our data suggest that the preventive effects of isoflavones on bone loss and fat accumulation in early postmenopausal women depend on an individual's equol-producing capacity.

Increased probiotic yogurt or resistant starch intake does not affect isoflavone bioavailability in subjects consuming a high soy diet

Objective Probiotics and prebiotics that affect gut microflora balance and its associated enzyme activity may contribute to interindividual variation in isoflavone absorption after soy intake, possibly enhancing isoflavone bioavailability. This study examined the effects of the consumption of bioactive yogurt (a probiotic) or resistant starch (a known prebiotic) in combination with high soy intake on soy isoflavone bioavailability. Methods Using a crossover design, chronic soy consumption was compared with soy plus probiotic yogurt or resistant starch in older male and postmenopausal females ( n = 31). Isoflavone bioavailability was assessed at the beginning and end of each 5-wk dietary period by sampling plasma and urine after a standardized soy meal. Results Chronic soy intake did not significantly affect plasma or urinary isoflavones after the soy meal and there were no significant effects of probiotic or resistant starch treatment. However, there were trends for increased circulating plasma daidzein and genistein after the probiotic treatment and for increased plasma daidzein and genistein 24 h after soy intake with resistant starch treatment. Neither treatment induced or increased equol production, although there was a trend for increased plasma equol in “equol-positive” subjects ( n = 12) after probiotic treatment. Conclusion The weak or absence of effects of probiotic yogurt or resistant starch supplement to a chronic soy diet suggests that gut microflora were not modified in a manner that significantly affected isoflavone bioavailability or metabolism.

Metabolism of dietary soy isoflavones to equol by human intestinal microflora – implications for health

Soy isoflavones have received considerable attention. Individuals with isoflavones-rich diets have significantly lower occurrences of cardiovascular disease, osteoporosis, and some cancers. The clinical effectiveness of soy isoflavones may be a function of the ability to biotransform soy isoflavones to the more potent estrogenic metabolite, equol, which may enhance the actions of soy isoflavones, owing to its greater affinity for estrogen receptors, unique antiandrogenic properties, and superior antioxidant activity. However, not all individuals consuming daidzein produce equol. Only approximately one-third to one-half of the population is able to metabolize daidzein to equol. This high variability in equol production is presumably attributable to interindividual differences in the composition of the intestinal microflora, which may play an important role in the mechanisms of action of isoflavones. But, the specific bacterial species in the colon involved in the production of equol are yet to be discovered. Therefore, future researches are aimed at identifying the specific bacterial species and strains that are capable of converting daidzein to equol or increasing equol production.

Metabolism of isoflavones, lignans and prenylflavonoids by intestinal bacteria: producer phenotyping and relation with intestinal community

Many studies have investigated the importance of the intestinal bacterial activation of individual phytoestrogens. However, human nutrition contains different phytoestrogens and the final exposure depends on the microbial potential to activate all different groups within each individual. In this work, interindividual variations in the bacterial activation of the different phytoestrogens were assessed. Incubation of feces from 100 individuals using SoyLife EXTRA, LinumLife EXTRA and isoxanthohumol suggested that individuals could be separated into high, moderate and low O-desmethylangolensin (O-DMA), equol, enterodiol (END), enterolactone (ENL) or 8-prenylnaringenin producers, but that the metabolism of isoflavones, lignans and prenylflavonoids follows separate, independent pathways. However, O-DMA and equol production correlated negatively, whereas a positive correlation was found between END and ENL production. In addition, END production correlated negatively with Clostridium coccoides-Eubacterium rectale counts. Furthermore, O-DMA production was correlated with the abundance of methanogens, whereas equol production correlated with sulfate-reducing bacteria, indicating that the metabolic fate of daidzein may be related to intestinal H(2) metabolism.

Review of the Factors Affecting Bioavailability of Soy Isoflavones in Humans

Soy isoflavones have anticarcinogenic, antioxidant, and antiatherosclerotic activities. They also interact with the estrogen receptor, which makes them weak or moderate phytoestrogens. Because of their bioactivity, isoflavone bioavailability has been extensively studied in humans. This review summarizes data from intervention studies in humans, focusing on the factors that affect bioavailability. Summarizing data from 16 studies shows that the maximum concentration in plasma normalized to a constant dose of genistin is ∼1.6 times that of genistein, and daidzin is ∼1.8-fold higher than daidzein, whereas the half-life is not significantly different for aglycone and glucoside. There is a wide variation in the reported percentage urinary excretion that is not dependent on dose. Bioavailability is increased by a rapid gut transit time and by low fecal digestion rates and is decreased by a fiber-rich diet. There is no difference in bioavailability between pre- and postmenopausal women. The daily ingestion of soymilk for 1 wk does not affect bioavailability, but daily ingestion for a month increases excretion of equol in women. The factors or habitual diet characteristics that influence equol production are not clear, but equol production is limited with an immature flora. There is no consensus on which source of isoflavones results in the highest isoflavone bioavailability, and published studies present different results, although bioavailability is affected by whether the dose is given as food or drink. In conclusion, it is important to consider the factors affecting bioavailability of isoflavones when designing intervention studies.