Genistein supplement side effects and benefits, isoflavone, daidzein phytoestrogen - Soybean extract
Feb 24 2014 by Ray Sahelian, M.D.

Genistein is an important nutraceutical molecule found in soybean. 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, 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. Genistein is a phytoestrogen with a wide variety of pharmacological effects.

Source Naturals purchase Genistein and Daidzen, Isoflavones, 1000 mg

Genistein has been the focus of scientific research since 1966. Studies have shown that it can bind to the same receptor sites as estrogen. Soybeans are the only significant dietary source; 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.

 

 

 

Purchase 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 is 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 this prostate formula.

With Saw Palmetto, Pygeum, Stinging Nettle, Quercetin, and several important Ingredients for support of normal prostate size and urine flow 

 

 

 

Saw Palmetto extract (standardized to contain 45% fatty acids - serenoa repens fruit)
Stinging Nettle 4:1 extract
Quercetin flavonoid extract
Rosemary 4:1 extract (Rosemarinus officinales leaf)
Beta Sitosterol extract.
Pygeum Africanum 4:1 bark extract
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

Review of health benefit
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.

Research interpretation
Nutr Rev. 2013 August. Pleiotropic effects of genistein in metabolic, inflammatory, and malignant diseases. This soy-derived biologically active isoflavone exhibits diverse health-promoting effects. An increasing body of evidence shows that it influences lipid homeostasis and insulin resistance, counteracts inflammatory cytokines, and possesses antidiabetic properties. It also impedes cancer progression by promoting apoptosis, inducing cell cycle arrest, modulating intracellular signaling pathways, and inhibiting angiogenesis and metastasis of neoplastic cells. This review summarizes the many functions of genistein in common health disorders such as metabolic syndrome, chronic inflammatory diseases, and cancer.

Antioxidant
Genistein appears to have excellent antioxidant ability.

The effect of genistein supplementation on performance and antioxidant status of Japanese quail under heat stress.
Arch Anim Nutr. 2004.
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.

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

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

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.

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.

Breast cancer
Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappaB/AP-1-dependent and -independent pathways.
 Int J Oncol. 2004.
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. Our results suggest that dietary soy isoflavones inhibit adhesion and motility of highly invasive breast cancer cells by distinct signaling pathways.

Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study.
Int J Cancer. 2004.
A diet high in isoflavonoids 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. 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. 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.

Ovarian cancer
Inhibitory effect of genistein and daidzein on ovarian cancer cell growth.
Anticancer Res. 2004.
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. 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.

Prostate cancer
Prostate. November 2013. Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells.

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.

Lung health, asthma
Dietary intake of soy genistein is associated with lung function in patients with asthma.
J Asthma. 2004.
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. Increasing consumption of genistein is associated with better lung function in patients with asthma.

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

The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial.
Am J Clin Nutr. 2004.
Isoflavone phytoestrogen therapy has been proposed as a natural alternative to hormone replacement therapy. 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 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

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

Role in thyroid health and function
In a 2007 clinical trial, Italian researchers found that genistein supplements, along with calcium and vitamin D, appeared to help boost bone mass in postmenopausal women with thinning bones.In this latest study, the researchers evaluated data from the same clinical trial -- this time looking at whether the genistein supplements had any effects on the women's thyroid function.The question stems from lab research showing that genistein and other isoflavones may decrease thyroid-hormone production. Thyroid hormones help govern metabolism, and an underactive thyroid gland, called hypothyroidism, can lead to problems like fatigue, weight gain and intolerance to cold.The earlier research suggested that isoflavones can affect thyroid hormones by interfering with iodine, which is needed for thyroid- hormone production, explained Dr. Francesco Squadrito of the University of Messina, the senior researcher on the study.However, he told Reuters Health by email, those studies used genistein doses that were 10 to 250 times higher than the doses used in his team's clinical trial -- 54 milligrams (mg) per day.Squadrito and his colleagues found that among 77 study participants they followed for three years, those who used the genistein supplement during that time showed no overall differences in thyroid function compared with women who were given a placebo.The findings are published in the Journal of Clinical Endocrinology and Metabolism.According to Squadrito, it is not surprising that studies would find thyroid effects of very high doses of genistein. However, he said, women are unlikely to consume such levels from soy-protein products, or from soy foods like tofu.As far as thyroid function is concerned, Squadrito said, "it is possible to conclude that genistein therapy is safe in postmenopausal women -- at least at the dose of 54 mg a day."However, soy contains several types of isoflavones, and more studies are needed to establish the safety of those compounds, according to Squadrito and his colleagues.SOURCE: Journal of Clinical Endocrinology and Metabolism, online March 31, 2010.

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).

Chemistry, synthesis and metabolism
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. It is a phytoestrogen with a wide variety of pharmacological effects in animal cells, including tyrosine kinase inhibition.

Genistein studies
Anticancer therapeutic potential of soy isoflavone, genistein.
Adv Exp Med Biol. 2004.
Genistein 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 it may reduce the risk of tumor formation. It 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, it 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. It 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. 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 alone or in combination with chemotherapy, radiation therapy, and/or immunotherapies. 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.

Phytoestrogen tissue levels in benign prostate hyperplasia and prostate cancer and their association with prostate diseases.
Urology. 2004 Oct.
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.
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.
After provocation of atherosclerosis with hyperlipidemic diet, 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.
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.

Soy isoflavones and cancer prevention.
Sarkar FH, Li Y. Wayne State University School of Medicine, Detroit, MI
Cancer Invest. 2003.
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.