Genistein supplement side effects and benefits, isoflavones, daidzein phytoestrogen - Soybean extract - by Ray Sahelian, M.D.

Genistein is an important nutraceutical molecule found in soybean. Genistein is a phytoestrogen with a wide variety of pharmacological effects. The average daily intake of genistein and genistin by the Japanese is 7 to 12 mg per person. Americans and Europeans have a much lower intake. Genistein is present in a product called Prostate Power Rx, see below.

Genistein and Daidzen, Isoflavones, 1000 mg
Source Naturals
Genistein, an isoflavone phytonutrient derived from soybeans, has been the focus of scientific research since 1966. Studies have shown that genistein can bind to the same receptor sites as estrogen. Soybeans are the only significant dietary source of genistein; however, the amount of soy foods necessary to meet the body's needs can be difficult to incorporate into today's diet. In Asia, where soy is a staple, the daily intake can be up to 20 times that of a Western diet. Source Naturals Genistein is made from isoflavone-rich soybean powder that yields a consistent standardized isoflavone content. This unique chemical-free process requires approximately 400 pounds of soybeans to yield just one pound of finished product.

Click here to purchase Genistein supplement, Prostate Power Rx, or to see a complete list of products at Physician Formulas
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Genistein Supplement Facts:
Amount Per 2 tablets:
Isoflavone-Rich - 2 g
Soybean Powder ( Soylife ) Yielding:
   Daidzein - 34 mg
   Glycitein - 20 mg
   Genistein - 8 mg
   Total Isoflavones - 62 mg

Suggested Use: One genistein tablet a few times a week with breakfast, or as recommended by your health care professional.

Prostate Power Rx with Genistein and Daidzein
Formulated by Ray Sahelian, M.D.

With Saw Palmetto, Pygeum, Stinging Nettle, Quercetin, & 9 Key Ingredients for support of normal prostate size & urine flow

Prostate Power Rx is carefully formulated with important herbs and nutrients to provide optimal prostate health. Significant clinical research on prostate enlargement has been conducted with the potent herbs in Prostate Power Rx. This prostate formula has been designed to support:

Saw Palmetto extract (standardized to contain 45% fatty acids - serenoa repens fruit)
Stinging Nettle 4:1 extract (urtica diocia root)
Quercetin flavonoid extract
Rosemary 4:1 extract (Rosemarinus officinales leaf)
Beta Sitosterol extract, see also
Beta-Sitosterol to purchase this supplement by itself.
Pygeum 4:1 bark extract (Pygeum Africanum)
Daidzein (standardized to contain 40% isoflavones)
  
(treatment with the isoflavones daidzein and genistein, the estrogen-like compounds found in soy, block prostate growth in rats)
Genistein (standardized to contain 40% isoflavones)
Lycopene (Lycoperscion escatatum fruit)

Genistein and your health
In spite of an extensive literature on the effects of dietary genistein, questions still exist as to its potential overall benefits as a component of the human diet. Dietary genistein ingestion has been linked, through epidemiological and animal model studies, with a range of potential health effects. These include prevention of breast, colon, and prostate cancers, cardiovascular disease and post-menopausal ailments. Genistein may also be helpful in decreasing bone loss after menopause.

Genistein and Prostate gland health
Genistein levels in prostate tissue are lower in those who have prostate cancer or an enlarged prostate.


Genistein Research interpretation

Genistein as an Antioxdiant
Genistein appears to have excellent antioxidant ability.

Asthma and lung function
Genistein may be associated with improved lung function in asthma.

Atherosclerosis or hardening of the arteries
A rabbit study shows genistein supplementation reduces the risk for hardening of the arteries.

Genistein and Blood pressure management

Chronic soy milk consumption has modest, but significant hypotensive action in those with hypertension. This hypotensive action was correlated with the urinary excretion of the isoflavone genistein.
Genistein helps produce more nitric oxide, a powerful chemical in the blood stream that helps dilate blood vessels.

Genistein, Hot flashes, and menopause
Genistein and other flavonoids do not appear to have a significant effect in reducing the severity of hot flashes, at least not as much as estrogen.

Gensitein and Osteoporosis influence, bone health
Genistein, along with other isoflavones, may help decrease bone loss after menopause.

Genistein and Cancer
Soy isoflavones may have an important role in reducing the incidence of breast, colon, cervix and prostate cancers. Genistein, the predominant isoflavone found in soy, has been shown to inhibit carcinogenesis in animal models. There is a growing body of experimental evidence that shows the inhibition of human cancer cells by genistein through the modulation of genes that are related to the control of cell cycle and apoptosis.

Sorting out isoflavones and phytoestrogens
Genistein, along with daidzein, are the best known and studied isoflavones. Isoflavones are types of flavonoids found in plants. Compounds from plants that have estrogen-like properties are called phytoestrogens.

The six major subclasses of flavonoids include:
Anthocyanidins (e.g., cyanidin, pelargonidin)
Catechins or flavanols (e.g., epicatechin, gallocatechin)
Flavones (e.g., apigenin, luteolin)
Flavonols (e.g., kaempferol, myricetin, quercetin)
Flavanones (e.g., hesperidin, naringenin)
Isoflavones (e.g., genistein, daidzein,
biochanin).

The chemistry of Genistein
Genistein, (also known as 4',5,7-trihydroxyisoflavone) is a common precursor in the biosynthesis of antimicrobial phytoalexins and phytoanticipins in legumes
. Genistein is synthesized in plants from the flavanone naringenin. Genistein is a phytoestrogen with a wide variety of pharmacological effects in animal cells, including tyrosine kinase inhibition.

Genistein Research studies
Dietary intake of soy genistein is associated with lung function in patients with asthma.
J Asthma. 2004;41(8):833-43.
To determine if micronutrient intake is associated with asthma severity, we administered the Block food frequency questionnaire to participants in a randomized clinical trial of the safety of influenza vaccine for asthmatics. The nutrition substudy included 1033 participants, aged 12-75. Intake of antioxidant vitamins, soy isoflavones, total fruits and vegetables, fats, and fiber was compared with asthma severity at baseline, peak expiratory flow rate (PEF), asthma symptoms and the rate of asthma exacerbations during the 2 weeks following influenza vaccination. The only nutrient that had a consistent association with asthma severity was genistein, a soy isoflavone. None of the nutrients evaluated were related to asthma exacerbation rate when adjusted for known confounders. The FEV1 in genistein consumers of at least 250 microg/1000 Kcal per day was 82% predicted, 79% predicted for those who consumed between 1 and 249 microg/1000 kcal, and 76% predicted in genistein nonconsumers; the PEF was 82% predicted, 80.8% predicted, and 78% predicted, respectively. Thus, increasing consumption of genistein is associated with better lung function in patients with asthma. Further studies are needed to determine whether dietary supplementation with genistein can reduce asthma severity.

Anticancer therapeutic potential of soy isoflavone, genistein.
Adv Exp Med Biol. 2004;546:121-65.
Ravindranath MH, Muthugounder S, Presser N, Viswanathan S. Laboratory of Glycoimmunotherapy, John Wayne Cancer Institute, 2200 Santa Monica Blvd., Santa Monica, CA
Genistein (4'5, 7-trihydroxyisoflavone) occurs as a glycoside (genistin) in the plant family Leguminosae, which includes the soybean (Glycine max). A significant correlation between the serum/plasma level of genistein and the incidence of gender-based cancers in Asian, European and American populations suggests that genistein may reduce the risk of tumor formation. Other evidence includes the mechanism of action of genistein in normal and cancer cells. Genistein inhibits protein tyrosine kinase (PTK), which is involved in phosphorylation of tyrosyl residues of membrane-bound receptors leading to signal transduction, and it inhibits topoisomerase II, which participates in DNA replication, transcription and repair. By blocking the activities of PTK, topoisomerase II and matrix metalloprotein (MMP9) and by down-regulating the expression of about 11 genes, including that of vascular endothelial growth factor (VEGF), genistein can arrest cell growth and proliferation, cell cycle at G2/M, invasion and angiogenesis. Furthermore, genistein can alter the expression of gangliosides and other carbohydrate antigens to facilitate their immune recognition. Genistein acts synergistically with drugs such as tamoxifen, cisplatin, 1,3-bis 2-chloroethyl-1-nitrosourea (BCNU), dexamethasone, daunorubicin and tiazofurin, and with bioflavonoid food supplements such as quercetin, green-tea catechins and black-tea thearubigins. Genistein can augment the efficacy of radiation for breast and prostate carcinomas. Because it increases melanin production and tyrosinase activity, genistein can protect melanocytes of the skin of Caucasians from UV-B radiation-induced melanoma. Genistein-induced antigenic alteration has the potential for improving active specific immunotherapy of melanoma and carcinomas. When conjugated to B43 monoclonal antibody, genistein becomes a tool for passive immunotherapy to target B-lineage leukemias that overexpress the target antigen CD19. Genistein is also conjugated to recombinant EGF to target cancers overexpressing the EGF receptor. Although genistein has many potentially therapeutic actions against cancer, its biphasic bioactivity (inhibitory at high concentrations and activating at low concentrations) requires caution in determining therapeutic doses of genistein alone or in combination with chemotherapy, radiation therapy, and/or immunotherapies. Of the more than 4500 genistein studies in peer-reviewed primary publications, almost one fifth pertain to its antitumor capabilities and more than 400 describe its mechanism of action in normal and malignant human and animal cells, animal models, in vitro experiments, or phase I/II clinical trials. Several biotechnological firms in Japan, Australia and in the United States (e.g., Nutrilite) manufacture genistein as a natural supplement under quality controlled and assured conditions.

The effect of genistein supplementation on performance and antioxidant status of Japanese quail under heat stress.
Arch Anim Nutr. 2004 Dec;58(6):463-71.
Genistein, a phytoestrogen found in soybeans, is a powerful antioxidant. We evaluated the effects of genistein supplementation on performance, carcass characteristics, levels of malondialdehyde (MDA), homocysteine, vitamins C, E, A in Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature of 34 degrees C. Results of the present study suggest that supplementation with genistein can be considered to be protective by reducing the negative effects of oxidative stress induced by heat stress in quail.

Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappaB/AP-1-dependent and -independent pathways.
 Int J Oncol. 2004 Nov;25(5):1389-95.
High consumption of soy products in some Asian countries has been linked to the low incidence of breast cancer in women. The chemopreventive effect of the soy isoflavone, genistein, has been observed through the suppression of cell proliferation, inhibition of angiogenesis and stimulation of apoptosis in breast carcinoma cells. Cancer metastasis consists of interdependent processes, including cell adhesion, migration and invasion. In the present study, we compare the effect of soy isoflavones in the form of aglycones (genistein, daidzein and glycitein) and glucosides (genistin, daidzin and glycitin) on the behavior of highly invasive breast cancer cells. Here we demonstrate that genistein suppresses cell adhesion and migration by inhibiting the constitutively active transcription factors NF-kappaB and AP-1, resulting in the suppression of secretion of urokinase-type plasminogen activator (uPA) in breast cancer cells. In addition, we show that all tested soy isoflavone aglycones (genistein, daidzein, glycitein) and glucosides (genistin, daidzin, glycitin) markedly reduced motility of MDA-MB-231 cells. However, only genistein and daidzein inhibited constitutively active NF-kappaB and AP-1 and suppressed secretion of uPA from breast cancer cells. Taken together, our results suggest that dietary soy isoflavones inhibit adhesion and motility of highly invasive breast cancer cells by distinct signaling pathways.

Phytoestrogen tissue levels in benign prostate hyperplasia and prostate cancer and their association with prostate diseases.
Urology. 2004 Oct;64(4):707-11.
Prostate tissue samples of men consuming a Western diet who underwent surgery for prostate enlargement or prostate cancer were collected and frozen. In the tissue samples, the enterolactone and genistein levels were determined. We subsequently compared the tissue levels in patients with prostate enlargement and prostate cancer and studied the impact of enterolactone and genistein on prostate volume. The enterolactone tissue levels were comparable in patients with prostate enlargement and prostate cancer and revealed no correlation to prostate volume. The genistein tissue levels tended to be lower in patients with prostate cancer compared with the entire prostate enlargement group. In addition, the genistein tissue levels were significantly greater in men with small-volume prostate enlargement compared with those with large-volume prostate enlargement. Our data suggest an involvement of genistein in the pathogenesis of prostate enlargement and, possibly, of prostate cancer. The impact of enterolactone is currently unknown.

Cardiovascular effects of the phytoestrogen genistein.
Curr Med Chem Cardiovasc Hematol Agents. 2004 Apr;2(2):179-86.
Phytoestrogenic molecules have received a great deal of attention over the last few years because of their potentially preventive roles against a few of today's most prevalent chronic diseases, namely cardiovascular diseases, osteoporosis and hormone related cancers. Of the several phytoestrogens, genistein in particular has been shown to be the most efficacious in animal models and experimental studies. Genistein in vitro relaxes rat arteries by a nitric oxide dependent mechanism and enhances the dilator response to acetylcholine of atherosclerotic arteries. Genistein supplementation improves endothelial dysfunction induced by oophorectomy in rats and reduces infarct size in an experimental model of myocardial ischaemia-reperfusion injury. Furthermore, genistein in postmenopausal women increases plasma nitric oxide breakdown products, reduces endothelin-1 levels and improves endothelial dependent vasodilation in post-menopausal women. All these findings, taken together, would suggest that this molecule might represent an attractive alternative for cardiovascular protection.

Genistein supplementation inhibits atherosclerosis with stabilization of the lesions in hypercholesterolemic rabbits.
J Korean Med Sci. 2004 Oct;19(5):656-61.
The effect of genistein on aortic atherosclerosis was studied in New Zealand White rabbits. After provocation of atherosclerosis with hyperlipidemic diet, the rabbits were divided as hyperlipidemic diet group (HD), normal diet group (ND) and hyperlipidemic plus genistein diet group (HD + genistein) for 4 and half months. The average cross sectional area of atherosclerotic lesion was 0.269 mm2 after provocation. The lesion was progressed by continuous hyperlipidemic diet (10.06 mm2) but was increased mildly by genistein (0.997 mm2), and decreased by normal diet. The ratio of macrophages to smooth muscle cells in the lesion was not changed by genistein supplementation. The western blotting showed reduction of MMP-3 expression in HD+genistein and ND groups than HD group. The inhibition of atherogenesis by genistein might be due to improved endothelial function rather than direct action on macrophages and/or smooth muscle cells in the lesion, since endothelial dysfunction by lipid peroxidation was the main atherogenic factor in the hypercholesterolemic rabbits. The genistein supplementation also suggests that it helps the stabilization of the atherosclerotic lesion by inhibition of MMP-3 expression.

Phytoestrogenic isoflavones daidzein and genistein reduce glucose-toxicity-induced cardiac contractile dysfunction in ventricular myocytes.
Endocr Res. 2004 May;30(2):215-23.
Epidemiological evidence suggests a reduction in the incidence of coronary heart disease, cancer and osteoporosis in populations with a high dietary intake of plant estrogen or phytoestrogen. The clinical benefit of phytoestrogens in cereals, vegetables and medicinal plants is attracting increasing attention for the general public. In the present study, we examined the effect of phytoestrogenic isoflavones daidzein and genistein on glucose toxicity-induced cardiac mechanical malfunction simulating diabetic cardiomyopathy. Adult rat ventricular myocytes were isolated and maintained for 24 hours in normal or high glucose medium in the absence or presence of isoflavones daidzein or genistein. Collectively, these data suggest that the phytoestrogenic isoflavones daidzein and genistein may reduce glucose toxicity-induced cardiac mechanical dysfunction and thus possess therapeutic potential against diabetes-associated cardiac defects.

Inhibition of proliferation and induction of apoptosis by genistein in colon cancer HT-29 cells.
Cancer Lett. 2004 Nov 25;215(2):159-66.
Genistein has multiple anticancer properties. However, its mechanisms of action and its molecular targets on human colon cells remain to be further elucidated. Here, we demonstrated that genistein reduced proliferation and induced G2/M phase arrest and apoptotic death in colon cancer HT-29 cells. We then investigated the effects of genistein on molecules that regulate apoptosis and cell cycle progress. Genistein increased expression of Bax and p21(WAF1) and slightly decreased Bcl-2 level. Our results demonstrated that genistein inhibited the viability of human colon cancer HT-29 cell via induction of apoptosis mainly through regulation of p21(WAF1) and Bax/Bcl-2 expression. These data suggested a role of genistein in prevention of colon tumor and might reduce colon tumor growth.

Inhibitory effect of genistein and daidzein on ovarian cancer cell growth.
Anticancer Res. 2004 Mar-Apr;24(2B):795-800.
Survival from ovarian cancer has not changed significantly in the past twenty years requiring development of additional treatment protocols. We studied the effect of genistein and daidzein on ovarian cancer cell growth. Five ovarian cancer cell lines from Stage IIIC disease were evaluated. Sulforhodamine B and colony formation assays were used to analyze growth inhibitory effects of genistein and daidzein alone and with cisplatin, paclitaxel or topotecan. Apoptosis induction was studied by determining caspase-3 activity. Inhibition of growth (50-80%), colony formation and colony size was seen at 144 microm of genistein, 0-23% reduction was demonstrated at 9 microm. At 144 microm, the colony size was inhibited >75%; at 9 microm 4/5 cell lines had >50% reduction. Caspase-3 activity was induced with all concentrations of genistein. Cisplatin and topotecan combined with genistein resulted in a mostly additive effect, paclitaxel was slightly less than additive. We demonstrate an inhibitory effect of genistein on ovarian cancer cell growth.

Not all soy products are created equal: caution needed in interpretation of research results.
Erdman JW Jr et al. University of Illinois, Urbana, IL
J Nutr. 2004 May;134(5):1229S-1233S.
Interest in the health benefits of soy foods has been intense among the research community, health professionals, and the public. At the same time, potential concerns associated with soy consumption, especially as related to soy isoflavones, have tempered the enthusiasm for making public health recommendations. On both accounts, the primary soybean isoflavone, genistein, has received the most attention. Because consumers are becoming increasingly confused by the often conflicting dietary messages, a balanced and accurate view of the risks and benefits of soy foods and soy food components is essential. Even among health professionals, confusion exists about proper nomenclature and about the precise composition of the agents under investigation. Levels of isoflavones are frequently assumed to be constant within categories of soy foods, and intakes are estimated rather than being directly analyzed. Furthermore, all too often research dealing singularly with genistein is interpreted by both health professionals and the media as equating directly with soy. Researchers often fail to fully understand the implications of their research outcomes and the context in which those outcomes should be placed. With the hundreds of publications yearly on soy and isoflavones, it is especially important to consider the literature in its entirety when making pronouncements about health effects.

Soy isoflavones and cancer prevention.
Sarkar FH, Li Y. Wayne State University School of Medicine, Detroit, MI
Cancer Invest. 2003;21(5):744-57.
Epidemiological studies have shown a significant difference in cancer incidence among different ethnic groups, which is believed to be partly attributed to dietary habits. The incidences of breast and prostate cancers are much higher in the United States and European countries compared with Asian countries such as Japan and China. One of the major differences in diet between these populations is that the Japanese and the Chinese consume a traditional diet high in soy products. Soy isoflavones have been identified as dietary components having an important role in reducing the incidence of breast and prostate cancers. Genistein, the predominant isoflavones found in soy, has been shown to inhibit the carcinogenesis in animal models. There are growing body of experimental evidence that show the inhibition of human cancer cells by genistein through the modulation of genes that are related to the control of cell cycle and apoptosis. Moreover, it has been shown that genistein inhibits the activation of NF-kappa B and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Genistein is commonly known as phytoestrogen, which targets estrogen- and androgen-mediated signaling pathways in the processes of carcinogenesis. Furthermore, genistein has been found to have antioxidant property, and shown to be a potent inhibitor of angiogenesis and metastasis. Taken together, both in vivo and in vitro studies have clearly shown that genistein, one of the major soy isoflavones, is a promising reagent for cancer chemoprevention and/or treatment. In this article, we attempt to provide evidence for these effects of genistein in a succinct manner to provide comprehensive state-of-the-art knowledge of the biological and molecular effects of the isoflavone genistein in cancer cells.

The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial.
Am J Clin Nutr. 2004 Feb;79(2):326-33.
Isoflavone phytoestrogen therapy has been proposed as a natural alternative to hormone replacement therapy (HRT). HRT has a beneficial effect on bone, but few trials in humans have investigated the effects of isoflavones on bone. The objective of the study was to determine the effect on bone density of a red clover-derived isoflavone supplement that provided a daily dose of 26 mg biochanin A, 16 mg formononetin, 1 mg genistein, and 0.5 mg daidzein for 1 y. Effects on biochemical markers of bone turnover and body composition were also studied. Women aged 49-65 y (n = 205) were enrolled in a double-blind, randomized, placebo-controlled trial; 177 completed the trial. Bone density, body composition, bone turnover markers, and diet were measured at baseline and after 12 mo. Loss of lumbar spine bone mineral content and bone mineral density was significantly lower in the women taking the isoflavone supplement than in those taking the placebo. There were no significant treatment effects on hip bone mineral content or bone mineral density, markers of bone resorption, or body composition, but bone formation markers were significantly increased in the intervention group compared with placebo in postmenopausal women. Interactions between treatment group and menopausal status with respect to changes in other outcomes were not significant. These data suggest that, through attenuation of bone loss, isoflavones have a potentially protective effect on the lumbar spine in women

Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study.
Int J Cancer. 2004 Jun 10;110(2):284-90.
A diet high in isoflavonoids (soy) is associated with lower breast cancer risk in Asian populations. Due to the low soy intake, dietary lignans may be the more important phytoestrogen class in Western populations. We used a population-based case-control study of breast cancer by age 50 in southern Germany to evaluate the association between dietary intake of different phytoestrogens and premenopausal breast cancer risk. Dietary information was collected from 278 premenopausal cases and 666 age-matched controls, using a validated FFQ. Using multivariate logistic regression, the highest vs. lowest intake quartiles of daidzein and genistein yielded significantly reduced ORs for breast cancer risk of 0.62 and 0.47, respectively. The protective effects of daidzein and genistein were found only for hormone receptor-positive tumors. High intake of other isoflavonoids, e.g., formononetin and biochanin A, as well as the sum of isoflavonoids were not associated with a decrease in risk. Breast cancer risk significantly decreased with a high intake of the plant lignan matairesinol but not secoisolariciresinol or the sum of plant lignans. However, both estimated mammalian lignans, enterodiol and enterolactone, were inversely associated with breast cancer risk, with ORs (95% CI) of 0.61and 0.57, respectively. No effect was found for total phytoestrogen intake. Our results suggest an important role of dietary intake of daidzein and genistein, despite low levels, as well as of matairesinol and mammalian lignans to reduce premenopausal breast cancer risk in this study population.