Herbal Science Research - isoflavone

[...] the growth stimulatory effect of soy and its isoflavones on established breast cancer

Site Editor — Sat, 23 Jun 2007 05:30:16 -0700

Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer?:

Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer?

Mol Nutr Food Res. 2007 Jun 20;

Authors: Power KA, Thompson LU

Consumption of phytoestrogen (PE)-rich foods (i. e., soy and flaxseed (FS)) is increasing because of their suggested health benefits. However, recent studies raise concern over the safety of soy and its isoflavones, particularly genistein (GEN), for postmenopausal breast cancer (BC), due to their potential stimulatory effects on human breast tissue and on the growth of existing tumors in rodents. FS, rich in PE lignans, which is metabolized to the mammalian lignans enterolactone (ENL) and enterodiol (END), has consistently been shown to have tumor inhibitory effects in a human clinical trial as well as rodent BC models. Using the preclinical athymic mouse postmenopausal BC model, combining FS with soy protein or GEN with END and ENL, was found to negate the tumor stimulatory effects of soy protein or GEN alone. The mechanism may be related to the modulation of estrogen receptor and MAPK signaling pathways. If these studies can be confirmed in clinical trials, then consumption of combined soy and FS, or their PEs, may reduce the tumor growth stimulatory effect of soy or GEN. This may indicate that if soy is consumed with lignan-rich foods, it may continue to induce its other beneficial health effects, without inducing adverse effect on postmenopausal BC.

PMID: 17579892 [PubMed - as supplied by publisher]

Molecular signatures of soy-derived phytochemicals in androgen-responsive prostate cancer cells: a comparison study...

Site Editor — Sat, 20 Jan 2007 16:30:02 -0800

Molecular signatures of soy-derived phytochemicals in androgen-responsive prostate cancer cells: a comparison study using DNA microarray.: Mol Carcinog. 2006 Dec;45(12):943-56 Authors: Takahashi Y, Lavigne JA, Hursting SD, Chandramouli GV, Perkins SN, Kim YS, Wang TT

The present study utilized microarray technology as a tool to elucidate the molecular signatures of soy-derived phytochemicals in the human androgen-responsive prostate cancer cell line LNCaP. Global gene expression pattern analysis of LNCaP cells exposed to 0, 1, 5, or 25 microM of the soy-derived phytochemicals equol and daidzein were conducted and compared. The data were further compared with previously generated data from exposure of LNCaP cells to the same doses of genistein, a soy isoflavone. Multidimensional scaling (MDS) analyses of the expression patterns suggest that these compounds exerted differential effects on gene expression in LNCaP cells. Further examination of specific gene changes revealed that these compounds differentially modulated genes in multiple cellular pathways, including the cell-cycle pathway genes. However, the three compounds also exerted similar effect on genes belonging to several other important cellular pathways. A universal effect of the three compounds on androgen-responsive genes, IGF-1 pathway gene, and MAP kinase-related pathway gene was observed. These results provide the foundation for establishing molecular signatures for equol, daidzein, and genistein. Moreover, these results also allow for the identification of candidate mechanism(s) by which soy phytochemicals and soy may act in prostate cancer cells.

Prolonged stabilization of platinum-resistant ovarian cancer in a single patient consuming a fermented soy therapy.

Site Editor — Fri, 09 Jun 2006 07:20:40 -0700

Prolonged stabilization of platinum-resistant ovarian cancer in a single patient consuming a fermented soy therapy.: Gynecol Oncol. 2006 Jan;100(1):205-9 Authors: Klein A, He X, Roche M, Mallett A, Duska L, Supko JG, Seiden MV

BACKGROUND: Women with ovarian cancer who experience disease progression during or within 6 months of first-line treatment with platinum-based anticancer drugs are considered to have platinum-resistant tumors. These patients have an unfavorable prognosis, and they frequently seek complementary and alternative therapies (CAM). Historically, this represents an understudied and underreported component of ovarian cancer treatment. CASE: This report describes the case of a woman with rapidly progressive, platinum-resistant ovarian cancer. Upon initiating self-directed treatment with Haelan951, a commercially available fermented soy beverage, she entered into a phase of prolonged disease stabilization including improvement in the serum tumor marker CA-125. CONCLUSION: Fermented soy products are known to contain high concentrations of the isoflavone, genistein, and other compounds that exhibit anticancer activity in preclinical models. This case report supports the prospective evaluation of alternative therapies such as these in patients with platinum-refractory ovarian cancer.

Crohn's disease leading to bowel cancer may be avoided by consumption of soya isoflavones: Adjunct-chemotherapy with oxaliplatin

Site Editor — Fri, 09 Jun 2006 04:26:43 -0700

Crohn's disease leading to bowel cancer may be avoided by consumption of soya isoflavones: Adjunct-chemotherapy with oxaliplatin.: Med Hypotheses. 2006 Jan 20; Authors: Wiseman A

Crohn's disease (inflammatory bowel syndrome) is caused by gut exposure to harmful reactive oxygen species (ROS) derived from oxygen, such as the superoxide anion (()O(2)(')), the hydroxyl radical (()OH) or the peroxide anion (O(2)('')): the superoxide anion is generated by breakdown of oxygen-peroxidised phospholipids membranes. Crohn's disease predisposes to bowel cancer in susceptible human sub-populations. It may be preventable in these as yet unpredictable sub-populations by dietary-based intervention strategies, such as the daily consumption of appropriate quantities of soya isoflavones. These isoflavonoids are ROS-directed antioxidants, and they include the phytoestrogens, daidzin and genistin present in soya foods (consumed also in dietary supplements). Oxaliplatin is a platinum-containing Pt(II) organometallic therapeutic agent that binds to tumour DNA. Oxaliplatin may provide, therefore, a form of chemotherapy for some bowel cancers especially when administered in adjunct-chemotherapies that employ inhibitors of proliferation of the tumour cell. Such inhibitors include 5-fluorouracil, which prevents the correct replication of tumour cell DNA that is an essential prerequisite for bowel tumour growth. Furthermore, the therapeutic index for adjunct-chemotherapy with toxic inhibitors of DNA replication and expression could potentially be raised significantly by an associated dietary regime. This should include supplementation daily, per or, with antioxidant isoflavones (or other bioflavonoids) in selected cases of unresponsive cancer of the bowel, to possibly seek to trigger the pathway of apoptosis (programmed cell death) in the tumour cells preferentially.

Estrogenic properties of isoflavones derived from Millettia griffoniana.

Site Editor — Fri, 09 Jun 2006 04:23:43 -0700

Estrogenic properties of isoflavones derived from Millettia griffoniana.: Phytomedicine. 2006 Feb;13(3):139-45 Authors: Ketcha Wanda GJ, Njamen D, Yankep E, Tagatsing Fotsing M, Tanee Fomum Z, Wober J, Starcke S, Zierau O, Vollmer G

In most developing countries, 70-80% of the population still resort to traditional medicine for their primary health care. This medicine utilises medicinal plants which are traditionally taken as concoction and infusion. The root and stem bark of Millettia griffoniana (Leguminosae), has been reported to contain isoflavonoids, alkaloids, and diterpenoids. The possible benefit of some bioactive isoflavones derived from M. griffoniana prompted us to screen them for estrogenic activity. Six isoflavones and coumarin derived from M. griffoniana (bail) namely, compound nos. 1-6 (Fig. 1) were tested for their potential estrogenic activities in three different estrogen receptor alpha (ERalpha)-dependent assays. In a yeast-based ERalpha assay, all test substances and 17beta-estradiol as endogenous agonist, showed a significant induction of beta-galactosidase activity. The test compounds at the concentration of 5x10(-6)M could achieve 59-121% of the beta-galactosidase induction obtained with 10(-8)M 17beta-estradiol (100%). In the reporter gene assay based on stably transfected MCF-7 cells (MVLN cells), the estrogen responsive induction of luciferase was also stimulated by the M. griffoniana isoflavones. In Ishikawa cells, all substances exhibited estrogenic activity revealed by the induction of alkaline phosphatase (AlkP) activity. The estrogenic activities of isoflavones from M. griffoniana could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ERalpha. Although all substances showed estrogenic effects, 4'-methoxy-7-O-[(E)-3-methyl-7-hydroxymethyl-2,6-octadienyl]isoflavone (7-O-DHF), Griffonianone C (GRIF-C), and 3',4'-dihydroxy-7-O-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone (7-O-GISO) were found to be the most potent of tested substances. In summary, estrogenic activities of the isoflavones derived from M. griffoniana were described for the first time using reporter gene assays and the estrogen-inducible AlkP Ishikawa model.

Pharmacokinetics of isoflavones, daidzein and genistein, after ingestion of soy beverage...

Site Editor — Fri, 09 Jun 2006 04:22:40 -0700

Pharmacokinetics of isoflavones, daidzein and genistein, after ingestion of soy beverage compared with soy extract capsules in postmenopausal Thai women.: BMC Clin Pharmacol. 2005;5(1):2 Authors: Anupongsanugool E, Teekachunhatean S, Rojanasthien N, Pongsatha S, Sangdee C

BACKGROUND: Isoflavones from soybeans may provide some beneficial impacts on postmenopausal health. The purpose of this study was to compare the pharmacokinetics and bioavailability of plasma isoflavones (daidzein and genistein) after a single dose of orally administered soy beverage and soy extract capsules in postmenopausal Thai women. METHODS: We conducted a randomized two-phase crossover pharmacokinetic study in 12 postmenopausal Thai women. In the first phase, each subject randomly received either 2 soy extract capsules (containing daidzin : genistin = 7.79 : 22.57 mg), or soy beverage prepared from 15 g of soy flour (containing daidzin : genistin = 9.27 : 10.51 mg). In the second phase, the subjects received an alternative preparation in the same manner after a washout period of at least 1 week. Blood samples were collected immediately before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 32 h after administration of the soy preparation in each phase. Plasma daidzein and genistein concentrations were determined by using high performance liquid chromatography (HPLC). The pharmacokinetic parameters of daidzein and genistein, i.e. maximal plasma concentration (Cmax), time to maximal plasma concentration (Tmax), area under the plasma concentration-time curve (AUC) and half-life (t1/2), were estimated using the TopFit version 2.0 software with noncompartmental model analysis. RESULTS: There were no significant differences in the mean values of Cmax/dose, AUC0-32/dose, AUC0- proportional, variant/dose, Tmax, and t1/2 of genistein between both preparations. For pharmacokinetic parameters of daidzein, the mean values of Cmax/dose, Tmax, and t1/2 did not significantly differ between both preparations. Nonetheless, the mean AUC0-32/dose and AUC0- proportional, variant/dose after administration of soy extract capsules were slightly (but significantly, p < 0.05) higher than those of soy beverage. CONCLUSION: The bioavailability of daidzein, which was adjusted for the administered dose (AUC/dose), following a single oral administration of soy beverage was slightly (but significantly) less than that of soy extract capsules, whereas, the bioavailability adjusted for administered dose of genistein from both soy preparations were comparable. The other pharmacokinetic parameters of daidzein and genistein, including Cmax adjusted for the dose, Tmax and t1/2, were not different between both soy preparations.

High concordance of daidzein-metabolizing phenotypes in individuals measured 1 to 3 years apart.

Site Editor — Fri, 09 Jun 2006 04:15:29 -0700

High concordance of daidzein-metabolizing phenotypes in individuals measured 1 to 3 years apart.: Br J Nutr. 2005 Dec;94(6):873-6 Authors: Frankenfeld CL, Atkinson C, Thomas WK, Gonzalez A, Jokela T, Wähälä K, Schwartz SM, Li SS, Lampe JW

Particular intestinal bacteria are capable of metabolizing the soya isoflavone daidzein to equol and/or O-desmethylangolensin (O-DMA), and the presence of these metabolites in urine after soya consumption are markers of particular intestinal bacteria profiles. Prevalences of equol producers and O-DMA producers are approximately 30-50 % and 80-90 %, respectively, and limited observations have suggested that these daidzein-metabolizing phenotypes are stable within individuals over time. Characterizing stability of these phenotypes is important to understand their potential as markers of long-term exposure to particular intestinal bacteria and their associations with disease risk. We evaluated concordance within an individual for the equol-producer and O-DMA-producer phenotypes measured at two time points (T1, T2), 1-3 years apart. Phenotypes were ascertained by analysing equol and O-DMA using GC-MS in a spot urine sample collected after 3 d soya (source of daidzein) supplementation. In ninety-two individuals without recent (within 3 months before phenotyping) or current antibiotics use, 41 % were equol producers at T1 and 45 % were equol producers at T2, and 90 % were O-DMA producers at T1 and 95 % were O-DMA producers at T2. The percentage agreement for the equol-producer phenotype was 82 and for the O-DMA-producer phenotype was 89. These results indicate that these phenotypes are stable in most individuals over time, suggesting that they provide a useful biomarker for evaluating disease risk associated with harbouring particular intestinal bacteria responsible for, or associated with, the metabolism of the soya isoflavone daidzein.

Menopause: a review of botanical dietary supplements.

Site Editor — Fri, 09 Jun 2006 04:14:55 -0700

Menopause: a review of botanical dietary supplements.: Am J Med. 2005 Dec 19;118(12 Suppl 2):98-108 Authors: Low Dog T

Since the release of the Women's Health Initiative (WHI) findings, an increasing number of dietary supplement products specifically targeting women in menopause have appeared in the American marketplace. This growth highlights the need for a critical evaluation of the tolerability and effectiveness of these products. The purpose of this article is to assess the evidence for safety and benefit of botanical monopreparations used for relief of menopause-related symptoms. The Cochrane Library and Medline databases were searched from January 1966 to October 2004, using a detailed list of terms related to botanicals and menopausal symptoms. Studies were considered eligible (1) if they were controlled trials of a botanical monopreparation administered orally for a minimum of 6 weeks to perimenopausal or postmenopausal women with hot flashes and (2) if they included a placebo or comparative treatment arm. Topical preparations, botanical combinations, and dietary interventions, such as soy food or protein, were not included. No language restrictions were imposed on the search. A total of 19 studies met the inclusion criteria. The majority of studies indicate that extract of black cohosh (Actaea racemosa L.) improves menopause-related symptoms; however, methodologic shortcomings in the trials were identified. To date, 4 case reports of possible hepatotoxicity have been published, although previous safety reviews suggest that black cohosh is well tolerated and that adverse events are rare when it is used appropriately. The results of 6 clinical studies on soy (Glycine max L.) isoflavone extracts are mixed. Moreover, the composition and dose of soy supplements varies widely across studies, making comparisons and definitive conclusions difficult. One study challenged the long-term safety of high-dose soy isoflavone extract (150 mg/day for 5 years) on the uterine endometrium. Clinical data from 5 controlled trials assessing the efficacy of semipurified isoflavone red clover (Trifolium pratense L.) leaf extracts to reduce hot flash frequency and severity or to relieve symptoms associated with the domains of the Greene Menopausal Symptom Scale are contradictory. The largest study showed no benefit for reducing symptoms associated with menopause for 2 different red clover isoflavone products compared with placebo. No significant adverse events have been reported in the literature. Single clinical trials do not support the use of dong quai (Angelica sinensis L.), ginseng (Panax ginseng C.A. Mey), or evening primrose seed oil (Oenothera biennis L.) for improving menopausal symptoms. We conclude that black cohosh extracts appear to ease menopausal symptoms; ongoing studies funded by the National Institutes of Health (NIH) will provide more definitive safety and efficacy data. Soy isoflavone extracts appear to have minimal to no effect, although definitive conclusions are difficult given the wide variation in product composition and dose. Long-term safety of higher dosage (150 mg/day) soy isoflavone extracts is uncertain. Semipurified isoflavone red clover leaf extracts have minimal to no effect in reducing menopausal symptoms. Dong quai, ginseng extract, and evening primrose seed oil appear to be ineffective in ameliorating menopausal symptoms at the dosages and in the preparations used in these studies.

Menopause: a review of botanical dietary supplements.

Site Editor — Fri, 09 Jun 2006 04:14:38 -0700

Menopause: a review of botanical dietary supplements.: Am J Med. 2005 Dec 19;118(12 Suppl 2):98-108 Authors: Low Dog T

Isoflavones modulate the glucuronidation of estradiol in human liver microsomes.

Site Editor — Fri, 09 Jun 2006 04:03:59 -0700

Isoflavones modulate the glucuronidation of estradiol in human liver microsomes.: Carcinogenesis. 2005 Dec;26(12):2172-8 Authors: Pfeiffer E, Treiling CR, Hoehle SI, Metzler M

Soy food has been associated with a reduced incidence of hormonal cancer in Asian countries, and the soy isoflavones daidzein and genistein are believed to protect against tumors induced by the endogenous hormone 17beta-estradiol (E2). In the present study, we have examined if daidzein and genistein as well as several structurally related isoflavones are able to modulate the in vitro glucuronidation of E2 in human hepatic microsomes. It is known that different isoforms of UDP-glucuronosyltransferase (UGT) are involved in E2 glucuronidation: UGT1A1 leads exclusively to the 3-glucuronide and is stimulated by E2 via homotropic kinetics, whereas UGT2B7 gives rise to the 17-glucuronide of E2 following Michaelis-Menten kinetics. In our study, daidzein markedly stimulated the 3-glucuronidation, thereby enhancing the metabolic clearance of E2. In contrast, genistein inhibited the 3-glucuronidation. The 17-glucuronidation of E2 was not affected by either compound. Formononetin and the daidzein metabolites equol, 3'-hydroxy-daidzein, 6-hydroxy-daidzein and glycitein behaved similar to daidzein, whereas biochanin A resembled genistein. The effect of daidzein on the 3-glucuronidation of E2 in human hepatic microsomes was also obtained with human recombinant UGT1A1. Since the only other compound known to stimulate E2 glucuronidation via allosteric kinetics is 17alpha-ethynylestradiol, our study is the first report of the heterotropic stimulation of a UGT by a non-steroidal and naturally occurring compound. An enhanced rate of glucuronidation of E2 by daidzein and its metabolites may contribute to the putative protection of soy against hormonal cancer.

Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women.

Site Editor — Fri, 09 Jun 2006 04:03:28 -0700

Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production.: Am J Clin Nutr. 2005 Dec;82(6):1260-8; quiz 1365-6 Authors: Hall WL, Vafeiadou K, Hallund J, Bügel S, Koebnick C, Reimann M, Ferrari M, Branca F, Talbot D, Dadd T, Nilsson M, Dahlman-Wright K, Gustafsson JA, Minihane AM, Williams CM

BACKGROUND: Dietary isoflavones are thought to be cardioprotective because of their structural similarity to estrogen. The reduction of concentrations of circulating inflammatory markers by estrogen may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease. OBJECTIVE: Our aim was to investigate the effects of isolated soy isoflavones on inflammatory biomarkers [von Willebrand factor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), E-selectin, monocyte chemoattractant protein 1, C-reactive protein (CRP), and endothelin 1 concentrations]. Differences with respect to single-nucleotide polymorphisms in selected genes [estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta [ERbeta (AluI) and ERbeta[cx] (Tsp509I), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), and cholesteryl ester transfer protein (TaqIB)] and equol production were investigated. DESIGN: One hundred seventeen healthy European postmenopausal women participated in this randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1; 50 mg/d) or placebo cereal bars were consumed for 8 wk, with a washout period of 8 wk between the crossover. Plasma inflammatory factors were measured at 0 and 8 wk of each study arm. RESULTS: Isoflavones improved CRP concentrations [odds ratio (95% CI) for CRP values >1 mg/L for isoflavone compared with placebo: 0.43 (0.27, 0.69)]; no significant effects of isoflavone treatment on other plasma inflammatory markers were observed. No significant differences in the response to isoflavones were observed according to subgroups of equol production. Differences in the VCAM-1 response to isoflavones and to placebo were found with ERbeta AluI genotypes. CONCLUSION: Isoflavones have beneficial effects on CRP concentrations, but not on other inflammatory biomarkers of cardiovascular disease risk in postmenopausal women, and may improve VCAM-1 in an ERbeta gene polymorphic subgroup.

Metabolism of glycitein (7,4'-dihydroxy-6-methoxy-isoflavone) by human gut microflora.

Site Editor — Fri, 09 Jun 2006 03:53:00 -0700

Metabolism of glycitein (7,4'-dihydroxy-6-methoxy-isoflavone) by human gut microflora.: J Agric Food Chem. 2005 Nov 2;53(22):8519-25 Authors: Simons AL, Renouf M, Hendrich S, Murphy PA

Gut microbial disappearance and metabolism of the soy isoflavone glycitein, 7,4'-dihydroxy-6-methoxyisoflavone, were investigated by incubating glycitein anaerobically with feces from 12 human subjects. The subjects' ages ranged from 24 to 53 years with a body mass index (BMI) of 20.9-25.8 kg/m(2) (mean BMI = 24.0 +/- 1.1 kg/m(2)). Glycitein disappearance followed an apparent first-order rate loss. Fecal glycitein disappearance rates for the subjects segregated into three different groups described as high (k = 0.67 +/- 0.14/h), moderate (k = 0.34 +/- 0.04/h), and low (k = 0.15 +/- 0.07/h) glycitein degraders (p < 0.0001). There was no dose effect on the disappearance rates for each subject from 10 to 250 microM glycitein (average k = 0.32 +/- 0.03/h, p > 0.05). Four putative glycitein metabolites, characterized by liquid chromatography-mass spectrometry (electrospray ionization using positive ionization mode), were dihydroglycitein, dihydro-6,7,4'-trihydroxyisoflavone, and 5'-O-methyl-O-desmethylangolensin. Two subjects produced a metabolite tentatively identified as 6-O-methyl-equol, and one subject produced daidzein as an additional metabolite of glycitein. These results show that glycitein is metabolized by human gut microorganisms and may follow metabolic pathways similar to other soy isoflavones.

Inhibition of collagenase by naturally-occurring flavonoids.

Site Editor — Fri, 09 Jun 2006 03:51:36 -0700

Inhibition of collagenase by naturally-occurring flavonoids.: Arch Pharm Res. 2005 Oct;28(10):1152-5 Authors: Sin BY, Kim HP

We examined the inhibitory activities of various flavonoids, including the flavanones, flavones/isoflavones and flavonols, on collagenase from Clostridium histolyticum to establish their therapeutic potential against skin inflammation and photoaging. In general, the flavonols were stronger inhibitors than the flavones/isoflavones, and this indicated the importance of the C-3 hydroxyl substitution. Quercetin was the most active flavonoid among those tested, and it showed an IC50 of 286 microM. These novel results suggest that certain flavonoids, particularly the flavonols, may prevent collagen breakdown by inhibiting collagenase in inflamed skin as well as photoaged skin.

Do soy isoflavones cause endometrial hyperplasia?

Site Editor — Fri, 09 Jun 2006 03:50:12 -0700

Do soy isoflavones cause endometrial hyperplasia?: Nutr Rev. 2005 Nov;63(11):392-7 Authors: Mahady GB

For many years, hormone replacement therapy (HRT) was considered the gold standard for the symptomatic treatment of menopause. Clinical trials have found that HRT reduces the symptoms of hot flashes and sweating, while also decreasing vaginal dryness and urinary tract infections. HRT has also been shown to be protective against colon cancer (37%) and hip fractures (34%). However, recent findings from the Women's Health Initiative (WHI) have revealed that long-term HRT may actually lead to an increase in heart disease (29%), breast cancer (26%) and other adverse events, such as stroke (41%). Consequently, many women in the United States and abroad are actively looking for alternative treatments for menopause, including botanical dietary supplements.

Hypertensive crisis associated with high dose soy isoflavone supplementation in a post-menopausal woman: a case report

Site Editor — Fri, 09 Jun 2006 03:26:05 -0700

Hypertensive crisis associated with high dose soy isoflavone supplementation in a post-menopausal woman: a case report:

Background: Isoflavones are gaining popularity as alternatives to hormone replacement therapy. However, few guidelines exist to inform the public as to an appropriate dose. This case involves a postmenopausal woman who experienced a hypertensive crisis while consuming a high-dose isoflavone supplement as part of a research protocol.Case PresentationThe participant was part of a placebo-controlled crossover trial to investigate the potential synergism of the antioxidant activity of soy isoflavones and vitamin C. Upon entry into the study, this healthy, well-nourished, normotensive postmenopausal woman (51 years old), consumed the first of four randomly assigned treatments (500 mg vitamin C plus 5 mg/kg body weight soy isoflavones). During this treatment, the participant's systolic blood pressure spiked to a recorded 226/117 mmHg, necessitating medical intervention and discontinuation of study participation. Two plausible mechanisms for this hypertensive crisis are discussed.
Conclusion: Due to the availability and increasing popularity of soy supplements, practitioners should be aware of the potential side effects associated with their use. Practitioners counseling clients who are consuming soy isoflavone supplements should advise them that elevated blood pressure may be a potential side-effect to consider and monitor.

Assessment of soy phytoestrogens' effects on bone turnover indicators in menopausal women with osteopenia in Iran...

Site Editor — Fri, 09 Jun 2006 03:25:44 -0700

Assessment of soy phytoestrogens' effects on bone turnover indicators in menopausal women with osteopenia in Iran: a before and after clinical trial:

Background: Osteoporosis is the gradual declining in bone mass with age, leading to increased bone fragility and fractures. Fractures in hip and spine are known to be the most important complication of the disease which leads in the annual mortality rate of 20% and serious morbidity rate of 50%. Menopause is one of the most common risk factors of osteoporosis. After menopause, sex hormone deficiency is associated with increased remodeling rate and negative bone balance, leading to accelerated bone loss and micro-architectural defects, resulting into increased bone fragility. Compounds with estrogen-like biological activity similar to "Isoflavones" present in plants especially soy, may reduce bone loss in postmenopausal women as they are similar in structure to estrogens.This research, therefore, was carried out to study the effects of Iranian soy protein on biochemical indicators of bone metabolism in osteopenic menopausal women. Materials and methodsThis clinical trial of before-after type was carried out on 15 women 45–64 years of age. Subjects were given 35 g soy protein per day for 12 weeks. Blood and urine sampling, anthropometric measurement and 48-h-dietary recalls were carried out at zero, 6 and 12 weeks. Food consumption data were analyzed using Food Proccessor Software. For the study of bone metabolism indicators and changes in anthropometric data as well as dietary intake, and repeated analyses were employed. Results: Comparison of weight, BMI, physical activity, energy intake and other intervening nutrients did not reveal any significant changes during different stages of the study. Soy protein consumption resulted in a significant reduction in the urinary deoxypyridinoline and increasing of total alkaline phosphatase (p < 0.05), although the alterations in osteocalcin, c-telopeptide, IGFBP3 and type I collagen telopeptide were not significant. Conclusion: In view of beneficial effect of soy protein on bone metabolism indicators, inclusion of this relatively inexpensive food in the daily diet of menopausal women, will probably delay bone resorption, thereby preventing osteoporosis.

Pharmacokinetics of isoflavones, daidzein and genistein, after ingestion of soy beverage compared with soy extract capsules...

Site Editor — Fri, 09 Jun 2006 03:23:55 -0700

Pharmacokinetics of isoflavones, daidzein and genistein, after ingestion of soy beverage compared with soy extract capsules in postmenopausal Thai women:

Background: Isoflavones from soybeans may provide some beneficial impacts on postmenopausal health. The purpose of this study was to compare the pharmacokinetics and bioavailability of plasma isoflavones (daidzein and genistein) after a single dose of orally administered soy beverage and soy extract capsules in postmenopausal Thai women. Methods: We conducted a randomized two-phase crossover pharmacokinetic study in 12 postmenopausal Thai women. In the first phase, each subject randomly received either 2 soy extract capsules (containing daidzin : genistin = 7.79 : 22.57 mg), or soy beverage prepared from 15 g of soy flour (containing daidzin : genistin = 9.27 : 10.51 mg). In the second phase, the subjects received an alternative preparation in the same manner after a washout period of at least 1 week. Blood samples were collected immediately before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 32 h after administration of the soy preparation in each phase. Plasma daidzein and genistein concentrations were determined by using high performance liquid chromatography (HPLC). The pharmacokinetic parameters of daidzein and genistein, i.e. maximal plasma concentration (Cmax), time to maximal plasma concentration (Tmax), area under the plasma concentration-time curve (AUC) and half-life (t1/2), were estimated using the TopFit version 2.0 software with noncompartmental model analysis. Results: There were no significant differences in the mean values of Cmax/dose, AUC0–32/dose, AUC0-∝/dose, Tmax, and t1/2 of genistein between both preparations. For pharmacokinetic parameters of daidzein, the mean values of Cmax/dose, Tmax, and t1/2 did not significantly differ between both preparations. Nonetheless, the mean AUC0–32/dose and AUC0-∝/dose after administration of soy extract capsules were slightly (but significantly, p less than 0.05) higher than those of soy beverage. Conclusion: The bioavailability of daidzein, which was adjusted for the administered dose (AUC/dose), following a single oral administration of soy beverage was slightly (but significantly) less than that of soy extract capsules, whereas, the bioavailability adjusted for administered dose of genistein from both soy preparations were comparable. The other pharmacokinetic parameters of daidzein and genistein, including Cmax adjusted for the dose, Tmax and t1/2, were not different between both soy preparations.

Isoflavones and Functional Foods Alter the Dominant Intestinal Microbiota in Postmenopausal Women.

Site Editor — Fri, 09 Jun 2006 03:12:20 -0700

Isoflavones and Functional Foods Alter the Dominant Intestinal Microbiota in Postmenopausal Women. - J Nutr. 2005 Dec;135(12):2786-2792 Authors: Clavel T, Fallani M, Lepage P, Levenez F, Mathey J, Rochet V, Sérézat M, Sutren M, Henderson G, Bennetau-Pelissero C, Tondu F, Blaut M, Doré J, Coxam V

Dietary phytoestrogens, such as isoflavones, are used as food additives to prevent menopause-related disorders. In addition to other factors, their bioavailability strongly depends on the activity of intestinal bacteria but the underlying interactions remain poorly understood. A randomized, double-blind, placebo-controlled study was undertaken with 39 postmenopausal women to characterize changes in the dominant microbial communities of the intestinal tract after 2 mo of isoflavone supplementation with and without pro- or prebiotic. The diversity and composition of the dominant microbiota were analyzed by temporal temperature-gradient gel electrophoresis (TTGE) and fluorescent in situ hybridization. Isoflavones alone stimulated dominant microorganisms of the Clostridium coccoides-Eubacterium rectale cluster, Lactobacillus-Enterococcus group, Faecalibacterium prausnitzii subgroup, and Bifidobacterium genus. The stimulation of the Clostridium coccoides-Eubacterium rectale cluster depended on the women's equol excretion and was transient, with the exception of a prolonged bifidogenic effect. Lasting changes in the diversity of the dominant species were also observed. The probiotic strain supplied could be detected by TTGE during its passage through the intestinal tract, and ingestion of fructooligosaccharides triggered a marked and specific bifidogenic effect. In conclusion, this is the first human study that shows changes in the diversity and composition of dominant bacterial communities in response to dietary supplementation with hormone-related compounds combined with functional foods.

Dietary flavonoids: Effects on xenobiotic and carcinogen metabolism.

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Dietary flavonoids: Effects on xenobiotic and carcinogen metabolism. - Toxicol In Vitro. 2005 Nov 10; Authors: Moon YJ, Wang X, Morris ME

Flavonoids are present in fruits, vegetables and beverages derived from plants (tea, red wine), and in many dietary supplements or herbal remedies including Ginkgo Biloba, Soy Isoflavones, and Milk Thistle. Flavonoids have been described as health-promoting, disease-preventing dietary supplements, and have activity as cancer preventive agents. Additionally, they are extremely safe and associated with low toxicity, making them excellent candidates for chemopreventive agents. The cancer protective effects of flavonoids have been attributed to a wide variety of mechanisms, including modulating enzyme activities resulting in the decreased carcinogenicity of xenobiotics. This review focuses on the flavonoid effects on cytochrome P450 (CYP) enzymes involved in the activation of procarcinogens and phase II enzymes, largely responsible for the detoxification of carcinogens. A number of naturally occurring flavonoids have been shown to modulate the CYP450 system, including the induction of specific CYP isozymes, and the activation or inhibition of these enzymes. Some flavonoids alter CYPs through binding to the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, acting as either AhR agonists or antagonists. Inhibition of CYP enzymes, including CYP 1A1, 1A2, 2E1 and 3A4 by competitive or mechanism-based mechanisms also occurs. Flavones (chrysin, baicalein, and galangin), flavanones (naringenin) and isoflavones (genistein, biochanin A) inhibit the activity of aromatase (CYP19), thus decreasing estrogen biosynthesis and producing antiestrogenic effects, important in breast and prostate cancers. Activation of phase II detoxifying enzymes, such as UDP-glucuronyl transferase, glutathione S-transferase, and quinone reductase by flavonoids results in the detoxification of carcinogens and represents one mechanism of their anticarcinogenic effects. A number of flavonoids including fisetin, galangin, quercetin, kaempferol, and genistein represent potent non-competitive inhibitors of sulfotransferase 1A1 (or P-PST); this may represent an important mechanism for the chemoprevention of sulfation-induced carcinogenesis. Importantly, the effects of flavonoids on enzymes are generally dependent on the concentrations of flavonoids present, and the different flavonoids ingested. Due to the low oral bioavailability of many flavonoids, the concentrations achieved in vivo following dietary administration tend to be low, and may not reflect the concentrations tested under in vitro conditions; however, this may not be true following the ingestion of herbal preparations when much higher plasma concentrations may be obtained. Effects will also vary with the tissue distribution of enzymes, and with the species used in testing since differences between species in enzyme activities also can be substantial. Additionally, in humans, marked interindividual variability in drug-metabolizing enzymes occurs as a result of genetic and environmental factors. This variability in xenobiotic metabolizing enzymes and the effect of flavonoid ingestion on enzyme expression and activity can contribute to the varying susceptibility different individuals have to diseases such as cancer. As well, flavonoids may also interact with chemotherapeutic drugs used in cancer treatment through the induction or inhibition of their metabolism.