Soy Isoflavones are thought to protect against cancer. They are found in soy-based food products. They suppress the production of stress proteins in cells, proteins that otherwise help cancer cells survive destruction by the immune system. They are antioxidant and also help lower cholesterol. Genistein inhibits angiogenesis, the growth of new blood vessels. When this growth is abnormal it can contribute to the development of cancer.
They are of help in hormone-dependent cancers (breast and prostate cancer), autoimmune conditions, high cholesterol, menopause, osteoporosis, benign prostatic hyperplasia and vaginitis
NOTE: This ingredient is only present in the Men's and Women's Plus formulas and NOT in the UNISEX formula, which is suitable for teenagers.
Published Clinical Studiesclin
Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial.
Chen YM, Ho SC, Lam SS, Ho SS, Woo JL.
Department of Community and Family Medicine, Chinese University of Hong Kong, Hong Kong.
Animal studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss, but few data are available in humans, especially in the Asian populations. This double-blind, placebo-controlled, randomized trial examines the effects of soy isoflavones on bone loss in postmenopausal Chinese women, aged 48-62 yr. Two hundred and three eligible subjects were randomly assigned to three treatment groups with daily doses of placebo (1 g starch; n = 67), mid-dose (0.5 g starch, 0.5 g soy extracts, and approximately 40 mg isoflavones; n = 68), and high dose (1.0 g soy extracts and approximately 80 mg isoflavones; n = 68). All were given 12.5 mmol (500 mg) calcium and 125 IU vitamin D(3). Bone mineral density (BMD) and bone mineral content (BMC) of the whole body, spine, and hip were measured using dual energy x-ray absorptiometry at baseline and 1 yr post treatment. Both univariate and multivariate analyses showed that women in the high dose group had mild, but statistically significantly, higher favorable change rate in BMC at the total hip and trochanter (P < 0.05) compared with the placebo and mid-dose groups, even after further adjustments for the potential confounding factors. Further stratified analyses revealed that the positive effects of soy isoflavone supplementation were observed only among women with lower initial baseline BMC (median or less). In conclusion, soy isoflavones have a mild, but significant, independent effect on the maintenance of hip BMC in postmenopausal women with low initial bone mass. Publication Types: " Clinical Trial " Randomized Controlled Trial
PMID: 14557449 [PubMed - indexed for MEDLINE]
The soy isoflavone genistein decreases adipose deposition in mice.2
Naaz A, Yellayi S, Zakroczymski MA, Bunick D, Doerge DR, Lubahn DB, Helferich WG, Cooke PS.
Department of Veterinary Biosciences, University of Illinois, Urbana, Illinois 61802, USA.
Adipose tissue is responsive to estrogen and expresses both estrogen receptor alpha and beta. To test the hypothesis that the estrogenic soy isoflavone genistein can have effects on adipose tissue, juvenile or adult C57/BL6 mice were ovariectomized and given daily injections of vehicle, 17beta-estradiol (5 microg/kg.d) or genistein (8-200 mg/kg.d) sc for 21-28 d. To test effects of dietary genistein, 25- to 27-d-old mice were fed diets containing 0-1500 parts per million (ppm) genistein for 12 d. Mice were killed and fat pads weighed. Parametrial fat pads were used for morphometric and Northern analysis. Genistein injections decreased adipose weight and adipocyte circumference at higher doses; effects in adult and juvenile mice were similar. Genistein decreased lipoprotein lipase mRNA, which may be a critical aspect of its adipose effects. Juveniles fed 500-1500 ppm dietary genistein had dose-responsive decreases in fat pad weights of 37-57%, compared with controls; 300 ppm genistein did not cause decreases. Genistein doses of 300, 500, 1000, and 1500 ppm produced serum genistein concentrations of 1.02 +/- 0.14 microM, 1.79 +/- 0.32 microM, 2.55 +/- 0.18 microM, and 3.81 +/- 0.39 microM, respectively. These results indicate dietary genistein at 500-1500 ppm produces antilipogenic effects in mice at serum levels that humans are realistically exposed to.
PMID: 12865308 [PubMed - indexed for MEDLINE]
The selective effect of genistein on the toxicity of bleomycin in normal lymphocytes and HL-60 cells.
Lee R, Kim YJ, Lee YJ, Chung HW.
School of Public Health and Institute of Health and Environmental Sciences, Seoul National University, 28 Yunkeun-dong, Chongno-ku, 110-460, Seoul, South Korea.
This study was carried out to find whether genistein might enhance bleomycin induced cytotoxicity in human leukemia (HL-60) while protecting normal blood lymphocytes. Despite the excellent chemotherapeutic effect of bleomycin, its cytotoxicity and genotoxicity in normal cells remains a major problem in chemotherapy.Genistein, one of the major Soy isoflavones, is particularly effective in quenching free radicals generated by toxic agents. In this study, the protective and enhancement effects of genistein on bleomycin induced cytotoxicity in HL-60 cells and blood lymphocytes were demonstrated. HL-60 cells were treated with various concentrations of genistein for 3h followed by treatment with various concentrations of bleomycin during the G(1) phase. Pretreatment of genistein increased micronuclei (MN) frequency and DNA damage as a result of bleomycin treatment.However, when human lymphocytes were pretreated with genistein prior to bleomycin treatment during the G(2) or G(0) phase, the frequencies of bleomycin induced MN was decreased. Although the extent of bleomycin induced DNA damage determined by single cell gel electrophoresis was increased through the pretreatment of genistein in HL-60 cells, it was decreased in normal lymphocytes. The result of this study may therefore provide great impact on the potential activity of genistein as a therapeutic agent.
PMID: 14751666 [PubMed - in process]
GENISTEIN AMELIORATES beta-AMYLOID PEPTIDE (25-35)-INDUCED HIPPOCAMPAL NEURONAL APOPTOSIS.
Zeng H, Chen Q, Zhao B.
Center of Brain & Cognitive Science, Institute of Biophysics, Academia Sinica, Beijing, People's Republic of China.
beta-Amyloid protein (Abeta), a major component of senile plaques of Alzheimer's disease (AD) brain, causes elevation of the intracellular free Ca(2+) level and the production of robust free radicals, both of which contribute greatly to the AD-associated cascade including severe neuronal loss in the hippocampus. Genistein, the most active molecule of soy isoflavones, protects diverse kinds of cells from damage caused by a variety of toxic stimuli. In the present study, we investigated the neuroprotective effect of genistein against Abeta(25-35)-induced apoptosis in cultured hippocampal neurons, as well as the underlying mechanism. Abeta(25-35)-induced apoptosis, characterized by decreased cell viability, neuronal DNA condensation, and fragmentation, is associated with an increase in intracellular free Ca(2+) level, the accumulation of reactive oxygen species (ROS), and the activation of caspase-3. All these phenotypes induced by Abeta(25-35) are reversed by genistein. Our results further show that at the nanomolar (100 nM) level, genistein protects neurons from Abeta(25-35)-induced damage largely via the estrogen receptor-mediated pathway, and at the micromolar (40 microM) level, the neuroprotective effect of genistein is mediated mainly by its antioxidative properties. Our data suggest that genistein attenuates neuronal apoptosis induced by Abeta(25-35) via various mechanisms.
PMID: 14744630 [PubMed - in process]
Inhibition of reactive nitrogen species effects in vitro and in vivo by isoflavones and soy-based food extracts.
Yen GC, Lai HH.
Department of Food Science, National Chung-Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan. firstname.lastname@example.org
Recent studies have shown that soy isoflavone inhibits inducible nitric oxide (NO) synthase activities and is reported to have peroxynitrite scavenging ability. Consequently, we investigated whether isoflavones (daidzein and genistein) and extracts from soy-based products (miso, soymilk, tofu, soy sprout, black soybean, soybean, and yuba) would inhibit the reactive nitrogen species (RNS) effect in vitro and in vivo. In the in vitro experiments [including the protection of cellular DNA from peroxynitrite or sodium nitroprusside damage, an inhibitory effect on nitric oxide production from lipopolysaccharide (LPS)-induced RAW 264.7 cells, and nitric oxide scavenging ability], extracts from soy-based foods showed a potent antioxidant activity and an inhibiting effect on RNS activity. These effects were correlated with total isoflavone content. In the in vivo experiments, rats were given isoflavones (4.0 mg/kg bw) or soy-based product extracts (1.0 g/kg bw) orally for 1 week and were injected with vehicle H(2)O (1 mL/kg bw) or LPS (10 mg/kg bw) on the day 7. Twelve hours after treatment, the rats were killed, and blood serum was collected for analysis. The intraperitoneal administration of LPS resulted in an increase in serum nitrite, nitrate, and nitrotyrosine concentrations. These are stable metabolite end products of nitric oxide, to 4-, 16-, and 5-fold levels, (4, 10 microM and 58 +/- 14 pmol/mL), of the placebo control, respectively. Results showed that oral administration of isoflavones and extracts from soy-based products significantly decreased serum nitrite, nitrate, and nitrotyrosine levels in LPS-induced rats. This study demonstrates that soy isoflavone supplementation may inhibit RNS-induced oxidation both in vitro and in vivo.
PMID: 14690370 [PubMed - in process]
Inhibitory effects of soy isoflavones on rat prostate carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[[!LB]]4,5-b[[!RB]]pyridine (PhIP).
Hikosaka A, Asamoto M, Hokaiwado N, Kato K, Kuzutani K, Kohri K, Shirai T.
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan; Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Intake of isoflavones derived from soybean products may impact on prostate cancer risk. Here we evaluated effects of Fujiflavone, a commercial isoflavone supplement, on rat prostate carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant heterocyclic amine in cooked meat. F344 male rats were given intragastric administrations of PhIP at the dose of 200mg/kg twice weekly for 10 weeks. The rats subsequently fed diet containing 0.25% Fujiflavone showed a significantly lower incidence of prostate carcinomas than those fed soy-free diet. Interestingly fewer carcinomas but more foci of prostatic intraepithelial neoplasia (PIN) were observed in the Fujiflavone group although the sum of the two lesions was not altered by Fujiflavone treatment. cDNA array analyses confirmed by semi-quantitative reverse transcription polymerase chain reactions (RT-PCR) revealed Fujiflavone to alter gene expression of ornithine decarboxylase (ODC), prothymosin alpha (PTA) in the rat prostate. No modification of PhIP-induced colon carcinogenesis was evident, except for increased multiplicity of ACF greater than 4 crypts in size. These results indicate that a commercial isoflavone supplement can inhibit PhIP-induced rat prostate carcinogenesis without any adverse effects, possibly by inhibiting progression of PIN to carcinoma, and that down-regulation of ODC and PTA could be related to the underlying mechanisms. Thus intake of dietary isoflavones can be promising for prevention of human prostate cancer.
PMID: 14656947 [PubMed - as supplied by publisher]
Soy isoflavones and cancer prevention.7
Sarkar FH, Li Y.
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, 715 Hudson Webber Cancer Center, 110 E. Warren, Detroit, MI 48201, USA. email@example.com
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.
PMID: 14628433 [PubMed - indexed for MEDLINE]
Lee HP, Gourley L, Duffy SW, et al. Dietary effects on breast-cancer risk in Singapore. Lancet 1991;337:1197–200.
Wei H, Bowen R, Cai Q, et al. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med 1995;208:124–9.
Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci 1993;90:2690–4.
Evans BA, Griffiths K, Morton MS. Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. J Endocrinol 1995;147:295–302.
Bennink MR, Mayle JE, Bourquin LD, Thiagarajan D. Evaluation of soy protein in risk reduction for colon cancer and cardiovascular disease: Preliminary results. Second International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. September 15–18, 1996. Brussels, Belgium.
Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 1993;342:1209–10.
Cassidy A, Bingham S, Setchell KDR. Biological effects of a diet of soy protein rich isoflavones on the menstrual cycle of premenopausal women. Am J Clin Nutr 1994;60:333–40.
Messina MJ. Legumes and soybeans: overview of their nutritional profiles and health effects. Am J Clin Nutr 1999;70:439S–50S.
Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 1995;333:276–82.
Potter SM. Overview of proposed mechanisms for the hypocholesterolemic effect of soy. J Nutr 1995;125:6065–115.
Potter SM, Baum JA, Teng H, et al. Soy protein and isoflavones: Their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998;68(suppl):1375S–79S.
Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol 1998;91:6–11.
Forsythe WA. Soy Protein, thyroid regulation and cholesterol metabolism. Forsythe WA. Soy protein, thyroid regulation and cholesterol metabolism. J Nutr 1995;125:619S–23S.
Ishizuki Y, Hirooka Y, Murata Y, Togashi K. [The effects on the thyroid gland of soybeans administered experimentally in healthy subjects.] Nippon Naibunpi Gakkai Zasshi 1991;67:622–9. [in Japanese].
Divi RL, Chang HC, Doerge DR. Antithyroid isoflavones from soybean. Biochem Pharmacol 1997;54:1087–96.
Teixeira SR, Potter SM, Weigel R, et al. Effects of feeding 4 levels of soy protein for 3 and 6 wk on blood lipids and apolipoproteins in moderately hypercholesterolemic men. Am J Clin Nutr 2000;71:1077–84.
Messina M. To recommend or not to recommend soy foods. J Am Diet Assoc 1994;94:1253–4.
Crouse JR 3rd, Morgan T, Terry JG, et al. A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Arch Intern Med 1999;159:2070–6.
Messina MJ, Persky V, Setchell KD, Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer 1994;21:113–31.
Anderson JJB, Ambrose WW, Garner SC. Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model (44243). Proc Soc Exp Biol Med 1998;217:345–50.