Soy, Isoflavones, Soybean, Tofu = Genistein Isoflavones, such as genistein and daidzein, are found in a number of plants including lupin, fava beans, soybeans, kudzu, and psoralea being the primary food source, also in the medicinal plants, Flemingia vestita and F. macrophylla, and coffee. Hundreds of studies say that more investigation is needed and cite numerous serious issues directly related to Soy/Genistein:
2000
Gee JM and others. Increased induction of aberrant crypt foci(clusters of abnormal tube-like glands in the lining of the colon and rectum) by 1,2-dimethylhydrazine in rats fed diets containing purified genistein or genistein-rich soya protein. Carcinogenesis 2000 Dec;21(12):2255-9. Genistein promotes induction of aberrant crypt foci by an as yet unidentified mechanism when fed immediately before treatment with 1,2-dimethylhydrazine.
2000
Cassanova N and others. Comparative effects of neonatal exposure of male rats to potent and weak (environmental) estrogens on spermatogenesis at puberty and the relationship to adult testis size and fertility: evidence for stimulatory effects of low estrogen levels. Endocrinology 2000 Oct;141(10):3898-907. Administration of genistein to rats significantly retarded most measures of pubertal spermatogenesis. Animals fed a soy-free diet had significantly larger testes than controls fed a soy-containing diet. “It is concluded that. . . the presence or absence of soy or genistein in the diet has significant short-term (pubertal spermatogenesis) and long-term (body weight, testis size, FSH levels and possibly mating) effects on males.”
2000
Watanabe S and others. Effects of isoflavone supplement on healthy women. Biofactors 2000;12(1-4):233-41. After one month of taking 20 mg or 40 mg isoflavones daily, 60% of the young women had prolonged menstruation, 20% had shortened menstruation, 17% remained unchanged and 3% became irregular. Other hormonal changes “suggest that isoflavones influence not only estrogen receptor-related functions but the hypothalamo-hypophysis-gonadal axis(hypothalamus, pituitary gland, and gonad).”
2000
Yang J and others. Influence of perinatal genistein exposure on the development of MNU-induced mammary carcinoma in female Sprague-Dawley rats. Cancer Lett 2000 Feb 28;149(1-2):171-9. “. . . perinatal genistein is an endocrine disrupter and increases the multiplicity of MNU-induced mammary carcinoma in rats.”
2000
Salti GI and others. Genistein induces apoptosis(cell death) and topoisomerase II-mediated DNA breakage(DNA damage) in coloncancer cells. Eur J Cancer 2000 Apr;36(6):796-802. DNA breakage in colon cancer cells occurred within 1 hour of treatment with genistein.
2000
Lephard ED and others. Phytoestrogens decrease brain calcium-binding proteins but do not alter hypothalamic androgen metabolizing enzymes in adult male rats. Brain Res 2000 Mar 17;859(1):123-31. Animals fed diets containing phytoestrogens for 5 weeks had elevated levels of phytoestrogens in the brain and a decrease of brain calcium-binding proteins. Calcium-binding proteins are associated with protection against neurodegenerative diseases.
2000
Strick R and others. Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia. Proc Natl Acad Sci USA 2000 Apr 25;97(9):4790-5. Researchers found that flavonoids, especially genistein, can cross the placenta and induce cell changes that lead to infant leukemia.
2000
Chang HS and Doerge DR. Dietary genistein inactivates rat thyroid peroxidase(thyroid/iodine) in vivo without an apparent hypothyroid effect. Toxicol Appl Pharmacol 2000 Nov 1;168(3):244-52. The activity of thyroid peroxidase activity in soy-fed rats was reduced by up to 80% compared to those on a soy-free diet. As thyroid hormone levels and thyroid weights were no different between treated and untreated groups, the researchers concluded that “the remaining enzymatic activity is sufficient to maintain thyroid homeostasis in the absence of additional perturbations.” However, it is difficult or impossible to measure some of the more subtle manifestations of hypothyroidism in rats.
2000
Gee JM and others. Increased induction of aberrant crypt foci by 1,2-dimethylhydrazine in rats fed diet containing purified genistein or genistein-rich soya protein. Carcinogenesis 2000;21:2255-2259. Rats fed the isoflavone genistein exhibited pathological changes in the colon.
2000
Ikeda T and others. Dramatic synergism between excess soybean intake and iodine deficiency on the development of rat thyroid hyperplasia. Carcinogenesis 2000 Apr;21(4):707-13. Excess soybean intake with iodine deficiency caused abnormal growth of the thyroid gland.
2001
Newbold RR and others. Uterine adenocarcinoma in mice treated neonatally with genistein. Cancer Res 2001 Jun 1;61(11):4325-8. Genistein in soy was found to be more carcinogenic than DES, especially during “critical periods of differentiation.. . . the use of soy-based infant formulas in the absence of medical necessity and the marketing of soy products designed to appeal to children should be closely examined.”
2001
de Lemos ML. Effects of soy phytoestrogens genistein and daidzein on breast cancer growth. Ann Pharmacother 2001 Sep;35(9):118-21. “Genistein and daidzein may stimulate existing breast tumor growth and antagonize the effects of tamoxifen. Women with current or past breast cancer should be aware of the risks of potential tumor growth when taking soy products.”
2001
Ju YH and others. Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice. J Nutr 2001 Nov;131(11):2957-62. Genistein stimulated breast tumor growth and cell proliferation in mice in a dose-responsive manner.
2001
Nagao T and others. Reproductive effects in male and female rats of neonatal exposure to genistein. Reprod Toxicol 2001 Jul-Aug;15(4):399-411. Feeding of genistein to newborn rats resulted in lower body weight in male and female rats, estrous cycle irregularities and lowered fertility in female rats. Neonatal exposure to genistein caused dysfunction of postpubertal reproduction performance as well as abnormal development of gonads in female but not in male rats.
2001
Allred CD and others. Dietary genistin stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein. Carcinogenesis 2001 Oct;22(10):1667-73. Genistin, the glycoside form of genistein, is converted to genistein by human saliva. The glycoside genistin, like the aglycone genistein, can stimulate estrogen-dependent breast cancer cell growth in vivo. Removal of genistin or genistein from the diet caused tumors to regress.
2002
Whitehead SA and others. Acute and chronic effects of genistein, tyrphostin and lavendustin A on steroid synthesis in luteinized human granulosa cells. Hum Reprod 2002 Mar;17(3):589-94. Genistein directly inhibits steroid-production enzymes.
2002
Klein SL and others. Early exposure to genistein exerts long-lasting effects on the endocrine and immune systems in rats. Mol Med 2002 Nov;8(11):742-9. Pregnant female rats were exposed to no, low (5 mg/kg diet) or high (300 mg/kg diet) genistein diets throughout gestation and lactation. At weaning, male offspring exposed to genistein perinatally were either switched to the genistein-free diet or remained on the genistein-dosed diets. At 70 days of age, immune organ masses, lymphocyte subpopulations, cytokine concentrations and testosterone concentrations were assessed in male offspring. Relative thymus masses were greater among males expose d to the high genistein diet than among males exposed to no genistein and certain markers of immune system function were also lower. Testosterone concentrations were lower among genistein-exposed than genistein-free males. These data illustrate that exposure to genistein during pregnancy and lactation exerts long-lasting effects on the endocrine and immune systems in adulthood. Whether exposure to phytoestrogens during early development affects responses to infectious or autoimmune diseases, as well ascancers, later in life requires investigation.
2002
Doerge DR and DM Sheehan. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect 2002 Jun;110 suppl 3:349-53. “Soy is known to produce estrogenic isoflavones. Here, we briefly review the evidence for binding of isoflavones to the estrogen receptor, in vivo estrogenicity and developmental toxicity, and estrogen developmental carcinogenesis in rats. Genistein, the major soy isoflavone, also has a frank estrogenic effect in women. We then focus on evidence from animal and human studies suggesting a link between soy consumption and goiter, an activity independent of estrogenicity. Iodine deficiency greatly increases soy antithyroid effects, whereas iodine supplementation is protective. . . . Although safety testing of natural products, including soy products, is not required, the possibility that widely consumed soy products may cause harm in the human population via either or both estrogenic and goitrogenic activities is of concern.”
2002
Ju YH and others. Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice. Cancer Res 2002 May 1;62(9):2474-7. Dietary genistein negated or overwhelmed the inhibitor effect of tamoxifen on tumor growth in ovariectomized and athymic mice. “Therefore, caution is warranted for postmenopausal women consuming dietary genistein while on TAM therapy for E-responsive breast cancer.”
2002
Guo TL and others. Genistein modulates splenic natural killer cell activity, antibody-forming cell response and phenotypic marker expression in F(0) and F(1) generations of Sprague-Dawley rats. Toxicol Appl Pharmacol 2002 Jun 15;181(3):219-27. Genistein caused a decrease in the percentage of helper T cells and an increase in the relative weights of spleen and thymus in rats.
2002
Kumar NB and others. The specific role of isoflavones on estrogen metabolism in premenopausal women.Cancer 2002 Feb 15;94(4):1166-74. Sixty eight women consuming 40 mg soy isoflavones daily for 12 weeks had changes in steroid hormones and increased cycle length.
2002
Chiang, CE and others. Genistein Inhibits the Inward Rectifying Potassium Current in Guinea Pig Ventricular Myocytes. J Biomed Sci 2002;9:321-326. Dietary isoflavones genistein dose-dependently and reversibly inhibit the inward rectifying K+ (potassium) current in guinea pigs ventricular myocytes, suggesting the potential for soy isoflavones to cause heart arrhythmias.
2002
Lephard ED and others. Neurobehavioral effects of dietary soy phytoestrogens. Neurotoxicol Teratol 2002 Jan-Feb;24(1):5-16. Male mice fed diets rich in phytoestrogens had lower levels of maze performance than male mice fed diets free of phytoestrogens. (Opposite results were observed in female mice.) The results indicate that consumption of dietary phytoestrogens resulting in very high plasma isoflavone levels (in many cases over a relatively short interval of consumption in adulthood) can significantly alter sexually dimorphic brain regions, anxiety, learning and memory.
2002
Newbold R and others. Increased uterine cancer seen in mice injected with genistein, a soy estrogen, as newborns. Cancer Research 2002 Jun 1;61(11):4325-8. Infant mice given genistein developed cancer of the uterus later in life. “The data suggest that genistein is carcinogenic if exposure occurs during critical periods in a young animal’s development.”
2003
Tsutsui T and others. Cell-Transforming Activity And Mutagenicity of 5 Phytoestrogens In Cultured Mammalian Cells. Int J Cancer 2003 105, 312-320. Phytoestrogens, such as Genistein and Dadzein, are responsible for the mutation of genes in mammals.
2004
Unfer V and others. Endometrial effects of long-term treatment with phytoestrogens randomized, double blind, placebo-controlled study. Fertil Steril 2004 Jul;82(1):145-8. Women treated with soy phytoestrogens for 5 years were more likely to suffer from endometrial hyperplasia than those treated with a placebo.
2004
Grace P and others. Phytoestrogen concentrations in serum and spot urine as biomarkers for dietary phytoestrogen intake and their relation to breast cancer risk in European prospective investigation of cancerand nutrition-norfolk. Cancer Epidemiol Biomarkers Prev. 2004 May;13(5):698-708. Women who had high concentration of Phystoestrogens were more likely to be at risk for breast cancer.
2005
Chen AC and others. Genistein Inhibits Intestinal Cell Proliferation in Piglets. Pediatric Research 2005, Vol. 57, No. 2, 192-200. Three groups of piglets were fed either sow milk replacer, sow milk replacer with small amounts of genistein and soy milk replacer with large amounts of genistein. The study found that those piglets who had consumed the large and small amounts of genistein had suffered from “reduced enterocyte proliferation and migration.”
Note: Enterocytes are cells which make up most of the inner surface of the intestine.
2005
Wood, C and others. Adrenocorticol Effects of Oral Estrogens and Soy Isoflavones in Female Monkeys. The Journal of Clinical Endocrinology and Metabolism 2005, Vol. 89 No. 5, 2319-2325. Three groups of female monkeys were fed either isoflavone depleted soy protein, soy protein with isoflavones or isoflavone depleted soy protein with conjugated equine estrogens, for 36 months. The group of monkeys fed the soy protein with isoflavones “had significantly lower adrenal weight… These findings suggest that long term estrogen treatment may contribute to an androgen-deficient and hypercortisolemic state.”
2006
Doerge D and others. Lactational transfer of the soy isoflavone genistein, in Sprague-Dawley rats consuming dietary genistein. Reprod Toxicol 2006 Apr;21(3):307-12. The study shows that small amounts of genistein are present in the milk of mothers who consumed the substance.
2006
Etcheverry P and others. Effect of Beef and Soy Proteins on the Absorption of Non-Heme Iron and Inorganic Zinc in Children. J Am Coll Nutr. 2006 Feb;25(1):34-40. Children who consumed beef meal had a “significantly greater” ability to absorb zinc and iron than those who consumed soy meal.
2006
Glover A and others. Acute exposure of adult male rats to dietary phytoestrogens reduces fecundity and alters epididymal steroid hormone receptor expression. Journal of Endocrinology (2006) 189, 565-573. “Adult males, fed a high phytoestrogen diet for 3 days, demonstrated significantly reduced fecundity… lipid peroxidation of epididymal sperm was significantly increased in animals fed a high phytoestrogen diet for 3 days. Disruption of the steroid regulation of the epididymis by phytoestrogens may alter its function, resulting in decreased quality of sperm, and thereby reducing fecundity.”
2006
Milerova J and others. Actual levels of soy phytoestrogens in children correlate with thyroid laboratory parameters. Clin Chem Lab Med 2006;44(2):171-4. Small differences in the amount of soy phytoestrogen consumed had moderately varying negative effects on the function of the thyroid gland.
2007
Jefferson W and others. Disruption of the female reproductive system by the phytoestrogen genistein.Reproductive Toxicology (2007) 23( 3), 308-16. Different amounts of Genistein fed to rats had adverse effect on the ovaries and estrogen cycle. Twenty five milligrams per kilogram caused lessened fertility and complete infertility was seen at fifty milligrams per kilogram. The offspring of females who consumed twenty five milligrams per kilogram of genistein were shown to have a larger number of multi-oocyte follicles(cysts), than those whose mothers had not, showing us that the effects of genistein can be carried for multiple generations. “Thus neonatal treatment with genistein at environmentally relevant doses caused adverse consequences on reproduction in adulthood.”
2007
Rachon D and others. Dietary daidzein and puerarin do not affect pituitary LH expression but exert uterotropic effects in ovariectomized rats. Maturitas 2007 Jun 20;57(2):161-70. “High dose consumption of commercially available preparations containing daidzein or puerarin may expose women with an intact uterus to the risk of endometrial hyperplasia.”
2007
Goodin S and others. Clinical and biological activity of soy protein powder supplementation in healthy male volunteers. Cancer Epidemiol Biomarkers Prev 2007;16:829–33. Twelve men 18 years or older were fed 56 grams of pure soy per day for 28 days. Over the 28 days the men experienced a 19% drop in serum testosterone.
2008
Chavarro J and others. Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic. Human Reproduction 2008, Vol. 23. No. 10, 2584-90. Those men who consumed considerable amounts of soy food had lower sperm concentration. These findings stayed consistent with “age, abstinence time, body mass index, caffeine and alcohol intake and smoking.”
2009
Eustache F and others. Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility. Environmental Health Perspec 2009 Aug;117(8):1272-9. “Chronic exposure to a mixture of a dose of phytoestrogen equivalent to that in the human diet and a low dose… of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility.”
2009
Jefferson W and others. Oral exposure to genistin, the glycosylated form of genistein, during neonatal life adversely affects the female reproductive system. Environmental Health Perspective 2009 Dec;117(12):1883-9. When female newborns are exposed genistin, (the glycosylated form of genistein), it can cause harm to the reproductive system. This harm took the form of “delayed vaginal opening… abnormal estrous cycles, decreased fertility, and delayed parturition.”
2009
Pastuszewska B and others. Nutritional value and physiological effects of soya-free diets fed to rats during growth and reproduction. J Anim Physiol Anim Nutr (Berl). 2008 Feb;92(1):63-74. The groups of rats fed egg and milk protein, instead of soy, showed superior reproductive performance.
2010
Sosic-Jurjevic, B and others. Suppressive effects of genistein and daidzein on pituitary-thyroid axis in orchidectomized middle-aged rats. Experimental Biology and Medicine 2010 May;235(5):590-8. Two groups of middle-aged rats were fed 10 milligrams per kilo of either Dazein or Genistein for three weeks and a third group was fed regular feed. “This study provides…direct evidence that (Genistein and Dadzein) can induce microfollicular changes in the thyroid tissue and reduce the level of thyroid hormones…”
2010
Yu C and others. Maternal exposure to daidzain alters behavior and oestrogen receptor alpha expression in adult female offspring. Behavioral Pharmacology May 2010. “Maternal exposure to daidzein has a masculinisation effect on memory and social behavior.”
2010
Ward H and others. Breast, colorectal, and prostate cancer risk in the European Prospective Investigation intoCancer and Nutrition-Norfolk in relation to phytoestrogen intake derived from an improved database. American Journal of Clinical Nutrition 2010 Feb;91(2):440-8. “Dietary phytoestrogens may contribute to the risk of colorectal cancer among women and prostate cancer among men.”
2010
Cimafranca M and others. Acute and chronic effects of oral genistein administration in neonatal mice. Biology of Reproduction 2010 Jul;83(1):114-21. This study was conducted in order “to develop a mouse model that more closely mimics the oral genistein exposure and total serum genistein concentrations observed in soy formula-fed infants.” Baby mice were fed soy formula until the fifth day after birth. The results showed that the “genistein treatment caused increased relative uterine weight and down-regulation of progesterone receptor in uterine epithelia. Estrogenic effects of genistein were also seen in the neonatal ovary and thymus, which had an increase in the incidence of multioocyte follicles (cysts) and a decrease in thymic weight relative to body weight, respectively. The increased incidence of MOFs persisted into adulthood for neonatally treated genistein females, and estrous cycle abnormalities were seen at 6 mo of age.”
2010
Cedarroth C and others. Potential detrimental effects of a phytoestrogen-rich diet on male fertility in mice.Molecular and Cellular Endocrinology 2010 Jun 10;321(2):152-60. Two groups of male mice were fed diets either containing large amounts of soy or no soy at all. The results showed “that long-term exposure to dietary soy and phytoestrogens may affect male reproductive function resulting in a small decrease in sperm count and fertility.”
2010
Balkrishnan B and others. Transplacental Transfer and Biotransformation of Genistein in the human placenta.Placenta 2010 June;31(6):506-511. Genistein has the ability to come through the placenta of healthy human fetuses.
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