A Systematic Review of the Effects of Equol (Soy Metabolite) on Breast Cancer.

Equol is a soy isoflavone metabolite that can be produced by intestinal bacteria. It is lipophilic and resembles natural oestrogens with an affinity to oestrogen receptors. This review is focused on how equol affects breast cancer, as evidenced by in vivo and in vitro studies. Equol is considered chemoprotective in specific endocrine-related pathologies, such as breast cancer, prostate cancer, cardiovascular diseases, and menopausal symptoms. In humans, not everyone can produce equol from gut metabolism. It is postulated that equol producers benefit more than non-equol producers for all the endocrine-related effects. Equol exists in two enantiomers of R-equol and S-equol. Earlier studies, however, did not specify which enantiomer was being used. This review considers equol's type and concentration variations, pathways affected, and its outcome in in vivo and in vitro studies.

Inter-relationship between diet, lifestyle habits, gut microflora, and the equol-producer phenotype: baseline findings from a placebo-controlled intervention trial.

OBJECTIVE: Equol is an active metabolite of isoflavones produced by gut microbiota. It is beneficial to health; however, equol-producing ability varies greatly among individuals. These variations depend on the host's gut microbiota and lifestyle habits including diet. We investigated the relationship between the gut microbiota, lifestyle habits including diet, and equol-producing ability in postmenopausal Japanese women. METHODS: We studied 58 postmenopausal Japanese women aged 48 to 69 years who visited the Sendai Medical Center in January, 2018. Self-administered questionnaires assessed their recent and remote food intake histories and lifestyle habits. Fecal microbiome analysis was performed using a next-generation sequencer. Urinary equol was measured using an immunochromatographic strip test. Women with urinary equol concentration >1.0 µM were defined as equol producers. RESULTS: Equol-producing bacteria were identified in 97% (56) of women; however, only 13 (22%) were equol producers. Equol producers showed significantly higher microflora diversity (P = 0.002), and significantly different recent and remote food intake patterns compared with equol nonproducers. Higher consumption of foods such as meat, fish, soy, vegetables, and Japanese snacks positively affected microbial diversity and equol production, whereas a high intake of Ramen and smoking showed negative effects. CONCLUSION: Equol production might not depend on the quantity, but on the quality of equol-producing bacteria. High microbial diversity might enhance equol production. Increasing microbial diversity through healthy lifestyle habits and habitual consumption of a wide variety of foods might be useful to maintain a healthy gut environment for equol production.

Byproducts of aqueous chlorination of equol and their estrogenic potencies.

While the phytoestrogen metabolite equol has been reported to exist in surface water, its behavior in drinking water treatment plants remains unrevealed. In this study, eight products including four chlorinated equols (monochloro-equol, dichloro-equol, trichloro-equol, and tetrachloro-equol) were identified in an aqueous chlorinated equol solution by UHPLC-quadrupole-orbitrap-HRMS. Two main pathways of chlorination reaction are proposed: (1) chlorine-substitution reactions on the aromatic ring and subsequent dehydration to form the chlorine-substituted equols, and (2) break-up of the heterocyclic ring with oxygen followed by oxidation of aldehyde to carboxyl. The human estrogen receptor (hER) activating activity for monochloro-equol (EC50 = 3456 nM) and dichloro-equol (EC50 = 2456 nM) were slightly stronger than that of equol (EC50 = 3889 nM). This is the first report on the behavior of equol in drinking water chlorination, which provided an important information on the risk assessment of equol in drinking water.

Changes in equol and major soybean isoflavone contents during processing and storage of yogurts made from control or isoflavone-enriched bovine milk determined using LC-MS (TOF) analysis.

The effect of supplementing a basal diet for dairy cows with "Soybean extract 40" (Biomedica, Prague, Czech Republic), containing 40% soybean isoflavones, on the contents of daidzein, glycitein, genistein, and equol in milk as well as fresh and mature yogurts was estimated. To determine the contents of these isoflavonoids, an efficient analytical LC-MS (TOF) technique was used. The "Soybean extract 40" used in our study contained an especially high proportion of daidzein (307gkg-1). In both milk and yogurt samples, the amounts of daidzein and its metabolite equol were significantly higher in samples obtained from cows that received the isoflavone extract-supplemented diet than from those that received the basal diet, as the precursor daidzein contributed to the increased equol concentrations. Fermentation caused significant changes in the daidzein and glycitein concentrations. With maturation, the concentrations of daidzein and equol were unaffected, while the glycitein concentration decreased significantly.

Urine and serum biomonitoring of exposure to environmental estrogens II: Soy isoflavones and zearalenone in pregnant women.

UNLABELLED: Urine and serum biomonitoring was used to measure internal exposure to selected dietary estrogens in a cohort of 30 pregnant women. Exposure was measured over a period comprising one-half day in the field (6 h) and one day in a clinic (24 h). Biomonitoring of the dietary phytoestrogens genistein (GEN), daidzein (DDZ) and equol (EQ), as well as the mycoestrogen, zearalenone (ZEN) and its congeners, was conducted using UPLC-MS/MS. Biomonitoring revealed evidence of internal exposure to naturally occurring dietary estrogens during pregnancy. Urinary concentrations of total GEN, DDZ and EQ were similar to levels reported for general adult U.S. POPULATION: Measurable concentrations of total (parent and metabolites) GEN, DDZ and EQ were present in 240, 207 and 2 of 270 serum samples, respectively. Six out of 30 subjects had measurable concentrations of unconjugated GEN and/or DDZ in serum between 0.6 and 7.1 nM. Urine to serum total isoflavone ratios for GEN, DDZ and EQ were 13, 47, and 180, respectively. ZEN and its reductive metabolite, α-zearalenol (α-ZEL), were present in pregnant women (11 out of 30 subjects) as conjugates at levels near the limit of quantification. The average total urinary concentration was 0.10 µg/L for ZEN and 0.11 µg/L for α-ZEL.

A survey of equol contents in Chinese stinky tofu with emphasis on the effects of cooking methods.

The equol contents of 32 samples of Chinese stinky tofu from different manufacturers in China mainland were determined. The results showed that 15 samples of raw stinky tofu contained substantial amounts of equol (1.16 ± 1.69 mg/100 g, wet basis), in which sample c-4 elicited the highest equol of 6.65 mg/100 g, whereas significantly lower equol contents were found in 17 fried samples (0.15 ± 0.14 mg/100 g, wet basis). A significant strong correlation between equol contents and the amino nitrogen contents (p < 0.01, Pearson correlation coefficient 0.725) was observed which indicated the eqoul content was associated with the fermentation extent. Cooking methods influenced the equol contents. Microwaving and frying tofu rapped with starch paste improved the equol contents, whereas deep frying, stir frying, and stewing had negative effects. The study demonstrated stinky tofu served as a good equol dietary source. Extensive fermentation and delicate cooking approaches were necessary for a high-equol final product.

[Separation of racemic flavonoids by high performance liquid chromatography using chiral mobile phase additive].

To perform chiral separation of three flavonoid racemates, including dihydrodaidzein, equol and alpinetin, a simple and effective method was developed by using sulfobutyl ether-beta-cyclodextrin (SBE-beta-CD) as a mobile phase additive in HPLC system. The effects of different factors on the chiral separation were investigated, including cyclodextrin (CD) types (alpha-CD, gamma-CD, beta-CD, methyl beta-CD), CD concentration (5, 10, 20 mmol/L), pH value, nature of organic solvents (methanol, ethanol, acetonitrile) and phosphate buffer concentration. The analysis was carried out on a Kromasil 100-5C18 column (250 mm x 4.6 mm, 5 microm). The mobile phase consisted of acetonitrile and 10 mmol/L SBE-beta-CD aqueous solution( containing 20 mmol/L KH2PO4, at pH 4.0 adjusted with phosphoric acid) (20: 80, v/v). The flow rate was set at 1 mL/min, the column temperature was 25 degrees C, and the UV detections of dihydrodaidzein, equol and alpinetin were carried out at 276, 280 and 290 nm, respectively. The established method was able to separate the three racemates, and the resolutions of the enantiomers (dihydrodaidzein, equol and alpinetin) were 1.8, 1.9 and 1.4, respectively. This method might be applied to separate various types of flavanoid enantiomers in chemical structure.

Discovery of an S-equol rich food stinky tofu, a traditional fermented soy product in Taiwan.

A recent epidemiological study showed that daily intake of mg quantities of S-equol is required for health-promoting effects in menopausal women. However, the maximum equol content in food was reported to be approximately 130 µg/100 g in egg yolk. The objective of this study was to find a high equol-containing food. We measured the equol content of 33 egg yolks and 21 fermented soybean foods. Equol was detected in 28 egg yolks at the maximum content of 43 µg/100 g. In the fermented soybean foods, equol was detected only in stinky tofu. We examined 16 stinky tofu samples purchased during different seasons and the average equol content was 1.39 mg/100 g, ranging from 0.34 to 2.68 mg/100 g. Equol was present in stinky tofu as the S-enantiomeric form and as an aglycon type. This is the first report demonstrating that stinky tofu contains high levels of S-equol, which may exert beneficial effects in menopausal women.