Abstract
Phytoestrogens, plant chemicals classified as isoflavones, coumestans and lignans, display estrogen-like activity because of their structural similarity to human estrogens and exhibit high affinity binding for the estrogen receptor β. They are common components of food items such as grains, beans, fruits and nuts. Isoflavones are primarily found in soybeans and foods made from soy. In particular, significant therapeutic properties have been generally attributed to soy isoflavones, but most of the claims have been poorly, or not at all, confirmed by well designed clinical trials. Such is the case of the purported role of soy isoflavones in reducing plasma cholesterol levels. This link is now not supported by many authors or by appropriately designed clinical studies. The role of isoflavones in cancer prevention, particularly of tumours under endocrine control (breast, prostate and others) is again only supported by weak to nonexisting clinical evidence. A similar case is that of the prevention/treatment of postmenopausal symptoms and osteoporosis. Disturbing data have been reported on potential negative effects of soy isoflavones on cognitive function in the aged, particularly relating to tofu intake. Recent studies have finally indicated a potential role for soy isoflavones in inducing chromosomal changes in cells exposed in vitro and potentiating chemical carcinogens. These findings may not, however, be extrapolated to clinical conditions. Available data do not appear to unequivocally support beneficial effects of soy isoflavones, and warn against their wide use, in the absence of satisfactory clinical findings.
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Walz E. Isoflavon- und saponin-glucoside in Soja-Hispida. Justus Liebigs Ann Chem 1931; 489: 118–55
Walter ED. Genistein (an isoflavone glucoside) and its aglucone, genistein, from soybeans. J Am Oil Chem Soc 1941; 63: 3273–6
Bennetts HW, Underwood EJ, Shier FL. A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust J Agric Res 1946; 22: 131–8
Axelson M, Sjovall J, Gustafsson B, Setchell KDR. Soya: a dietary source of the non-steroidal oestrogen equol in humans and animals. J Endocrinol 1984; 102: 49–56
Setchell KDR, Borriello SP, Hulme P, et al. Non-steroidal oestrogens of dietary origin: possible roles in hormone-dependent disease. Am J Clin Nutr 1984; 40: 569–78
Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med 1997; 95–120
van der Schouw YT, de Kleijn MJJ, Peeters PHM, et al. Phytooestrogen and cardiovascular disease risk. Nutr Metab Cardiovasc Dis 2000; 10: 154–67
Cassidy A, Bingham S, Setchell KDR. Biological effects of isoflavones present in soy in premenopausal women: implications for the prevention of breast cancer. Am J Clin Nutr 1994; 60: 33–40
Tikkanen MJ, Adlercreutz H. Dietary soy-derived isoflavone phytoestrogens. Biochem Pharmacol 2000; 60: 1–5
Washburn S, Burke GL, Morgan T, et al. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause 1999; 6: 7–13
Blair H, Jordan SE, Peterson T, et al. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. J Cell Biochem 1996; 61: 629–37
Setchell KDR, Nechemias-Zimmer L, Cai J, et al. Exposure of infants to phytoestrogens from soy infant formulas. Lancet 1997; 350: 23–7
Miksicek RJ. Estrogenic flavonoids: structural requirements for biological activity. Proc Soc Exp Biol Med 1995; 208(1): 44–50
Joannou GE, Kelly GE, Reeder AY, et al. A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids. J Steroid Biochem Mol Biol 1995; 54: 167–84
Xu X, Harris KS, Wang HJ, et al. Bioavailability of soybean isoflavones depends upon gut microflora in women. J Nutr0 1995; 125: 2307–15
Karr SC, Lampe JW, Hutchins AM, et al. Urinary isoflavonoid excretion in humans is dose dependent at low to moderate levels of soy-protein consumption. Am J Clin Nutr 1997; 66: 46–51
Wang HJ, Murphy PA. Isoflavone content in commercial soybean foods. J Agr Food Chem 1994; 42: 1666–73
Adlercreutz H, Honjo H, Higashi A, et al. Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet. Am J Clin Nutr 1991; 54: 1093–100
Adlercreutz H, Fotsis T, Bannwart C, et al. Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J Steroid Biochem 1986; 25: 791–7
Horn Ross PL, Barnes S, Kirk M, et al. Urinary phytoestrogen levels in youngwomen from a multiethnic population. Cancer Epidemiol Biomarkers Prev 1997; 6: 339–45
Ignatowski A. Über die Wirkung des tierischen Eiweisses auf die Aorta und die parenchymatösen Organen der Kaninchen. Virchow Arch Pathol Anat Physiol Klin Med 1909; 198: 248–70
Sirtori CR, Agradi E, Conti F, et al. Soybean-protein diet in the treatment of type II hyperlipoproteinaemia. Lancet, 1977; I: 275–8
Descovich GC, Ceredi C, Gaddi A, et al. Multicenter study of soybean protein diet for outpatient hypercholesterolaemic patients. Lancet 1980; II: 709–12
Sirtori CR, Gatti E, Mantero O, et al. Clinical experience with the soybean protein diet in the treatment of hypercholesterolemia. Am J Clin Nutr 1979; 32: 1645–58
Hermansen K, Sondergaard M, Hoie L, et al. Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects. Diabetes Care 2001; 24: 228–33
Anderson JW, Bryan MJ, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 1995; 333: 276–82
Sirtori CR, Gianazza E, Manzoni C, et al. Role of isoflavones in the cholesterol reduction by soy proteins in the clinic. Am J Clin Nutr 1997; 65: 166–7
Sirtori CR, Galli G, Lovati MR, et al. Effects of dietary proteins in the regulation of liver lipoprotein receptors in rats. J Nutr 1984; 114: 1493–1500
Lovati MR, Manzoni C, Corsini A, et al. Low density lipoprotein receptor activity is modulated by soybean globulins in cell culture. J Nutr 1992; 122: 1971–8
Lovati MR, Manzoni C, Corsini A. 7S globulin from soybean is metabolised in human cell cultures by a specific uptake and degradation system. J Nutr 1996; 126: 2831–43
Lovati MR, Manzoni C, Gianazza E, et al. Soybean protein products as regulators of liver low-density lipoprotein receptors. I. Identification of active β-conglycinin subunits. J Agr Food Chem 1998; 46: 2474–80
Lovati MR, Manzoni C, Gianazz E, et al. Soy protein peptides regulate cholesterol homeostasis in Hep G2 cells. J Nutr 2000; 130: 2543–9
Lovati MR, Manzoni C, Canavesi A, et al. Soybean protein diet increases low density lipoprotein receptor activity in mononuclear cells from hypercholesterolemic patients. J Clin Invest. 1987; 80: 1498–502
Baum JA, Teng H, Erdman JWJ, et al. Long term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women. Am J Clin Nutr 1998; 68: 545–51
FDA Talk Paper.Washington, D.C.: US Food and Drug Administration Press Office, 1999 Oct 20
Anthony MS, Clarkson TB, Hughes Jr CL, et al. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal Rhesus monkeys. J Nutr 1996; 126: 43–50
Anthony MS, Clarkson TB, Bullock BC, et al. Soy protein versus soy phytoestrogens in the prevention of diet induced coronary artery atherosclerosis of male Cynomolgus monkeys. Arterioscl Thromb Vasc Biol 1997; 17: 2524–31
Crouse JR III, Morgan R, Terry JG, et al. A randomised 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
Merz-Demlow BE, Duncan AM, Wangen KE, et al. Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women. Am J Clin Nutr 2000; 71: 1462–9
Greaves KA, Parks JS, Williams JK, et al. Intact dietary soy protein, but not adding an isoflavone-rich soy extract to casein, improves plasma lipids in ovariectomized cynomolgus monkeys. J Nutr 1999; 129: 1585–92
Greaves KT, Wilson MD, Rudel LL, et al. Consumption of soy protein reduces cholesterol absorption compared with casein alone or supplemented with an isoflavone extract or conjugated equine estrogen in ovariectomized cynomolgous monkeys. J Nutr 2000; 130: 820–26
Nestel PJ, Yamashita T, Sasahara T, et al. Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscl Thromb Vasc Biol 1997; 17: 3392–8
Simons LA, von Konigsmark M, Simons J, et al. Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women. Am J Cardiol 2000; 85: 1297–1301
Hodgson JM, Puddey IB, Beilin LJ, et al. Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentrations: a randomised controlled trial in humans. J Nutr 1998; 128: 728–32
Samman S, Lyons Wall PM, et al. The effect of supplementation with isoflavones on plasma lipids and oxidisability of low density lipoprotein in premenopausal women. Atherosclerosis 1999; 147: 277–83
Nestel PJ, Pomeroy S, Kay S, et al. Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women. J Clin Endocrinol Metab 1999; 84: 895–8
Howes JB, Sullivan D, Lai N. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profile of post menopausal women with mild to moderate hypercholesterolemia. Atherosclerosis 2000; 152: 143–7
Erdman JW. Soy protein and cardiovascular disease: a statement for healthcare professionals from the Nutrition Committee of the AHA. Circulation 2000; 102: 2555–9
Peluso MR, Winters TA, Shanahan MF, et al. A cooperative interaction between soy protein and its isoflavones-enriched fraction lowers hepatic lipids inmale obese Zucker rats and reduces blood platelet sensitivity in male Sprague-Dawley rats. J Nutr 2000; 130: 2333–42
Sfakianos J, Coward L, Kirk M. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. J Nutrition 1997; 127: 1260–8
Kirk EA, Sutherland P, Wang SA, et al. Dietary isoflavones reduce plasma cholesterol and atherosclerosis in C57BL/6 mice but not LDL receptor-deficient mice. J Nutr 1998; 128: 954–9
Jager W, Winter O, Halper B, et al. Modulation of liver canalicular transport processes by the tyrosine-kinase inhibitor genistein: implications of genistein metabolism in the rat. Hepatology 1997; 26: 1467–76
Jager W, Sartor M, Herzo W, et al. Genistein metabolism in liver microsomes of Wistar and mutant TR(-)-rats. Res Comm Mol Pathol Pharmacol 1998; 100: 105–16
Lamon-Fava S. Genistein activates apolipoproteins A-I gene expression in the human hepatoma cell line HepG2. J Nutr 2000; 130: 2489–92
Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr 1997; 353–81
Tikkanen MJ, Wahala K, Ojala S, et al. Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance. Proc Natl Acad Sci U S A 1998; 95: 3106–10
Wagner JD, Cefalu WT, Anthony MS, et al. Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgus monkeys. Metabolism 1997; 46: 698–705
Kapiotis S, Hermann M, Held I, et al. Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arterioscler Thromb Vasc Biol 1997; 17: 2868–74
Kerry N, Abbey M. The isoflavone genistein inhibits copper and peroxyl radical mediated low density lipoprotein oxidation in vitro. Atherosclererosis 1998; 140: 341–7
Wiseman H, O’Reilly JD, Adlercreutz H, et al. Isoflavone phytoestrogens consumed in soy decrease F2-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans. Am J Clin Nutr 2000; 72: 395–400
Jenkins DJ, Kendall CW, Vidgen E, et al. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am J Clin Nutr 1999; 69: 395–402
Hodgson JM, Puddey IB, Croft KD, et al. Isoflavonoids do not inhibit in vivo lipid peroxidation in subjects with high-normal blood pressure. Atherosclerosis 1999; 145: 167–72
Honoré EK, Williams JK, Anthony MS, et al. Soy isoflavones enhance vascular reactivity in atherosclerotic female macaques. Fertil Steril 1997; 67: 148–54
Anthony MS. Soy and cardiovascular disease: cholesterol lowering and beyond. J Nutr 2000: 130: 662S–3S
Walker HA, Dean TS, Sanders TAB, et al. The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17β-estradiol. Circulation 2001; 103: 258–62
Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 1993; 342: 1209–10
Williams JK, Clarkson TB. Dietary soy isoflavones inhibit in vivo constrictor responses of coronary arteries to collagen induced platelet activation. Coron Artery Dis 1998; 9: 759–64
Schoene NW, Guidry CA. Dietary soy isoflavones inhibit activation of rat platelets. J Nutr Biochem 1999; 10: 421–6
Kuiper GG, Lemmen JG, Carlsson B, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology 1998; 139: 4252–63
Mäkelä S, Savolainen H, Aavik E et al. Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors aand β. Proc Natl Acad Sci U S A 1999; 96: 7077–82
Shimokado K, Yokota T, Umezawa K, et al. Protein tyrosine kinase inhibitors inhibit chemotaxis of vascular smooth muscle cells. Arterioscler Thromb 1994; 14: 973–81
Shimokado K, Umezawa K, Ogata J. Tyrosine kinase inhibitors inhibit multiple steps of the cell cycle of vascular smooth muscle cells. Exp Cell Res 1995; 220: 266–73
Wagner JD, Zhang L, Greaves KA, et al. Soy protein reduces the arterial low-density lipoprotein (LDL) concentration and delivery of LDL cholesterol to the arteries of diabetic and nondiabetic male cynomolgus monkeys. Metabolism 2000; 49: 1188–96
Parkin DM. Cancers of the breast, endometrium and ovary: geographic correlations. Eur J Cancer Clin Oncol 1989; 25: 1917–25
Rose DP, Boyar AP, Wynder EL. International comparison of mortality rates for cancer of the breast, ovary, prostate and colon, and per capita food consumption. Cancer 1986; 58: 2363–71
Gao YH, Yamaguchi M. Inhibitory effect of genistein on osteoclast-like cell formation in mouse marrow cultures. Biochem Pharmacol 1999; 58: 767–72
Fanti P, Monier-Faugere MC, Geng Z, et al. The phytoestrogen genistein reduces bone loss in short term ovariectomized rats. Osteoporosis Int 1998; 8: 274–81
Kuiper GG, Enmark E, Pelto-Huikko M, et al. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996; 93: 5925–30
Kuiper GG, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997; 138: 863–70
Akiyama T, Ishida J, Nakagawa S, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 1987; 262: 5592–95
Sathyamoorthy N, Gilsdorf JS, Wang TT. Differential effect of genistein on transforming growth factor beta 1 expression in normal and malignant mammary epithelial cells. Anticancer Res 1998; 18: 2449–53
Kim H, Peterson TG, Barnes S. Mechanisms of action of the soy isoflavone genistein: emerging role of its effects through transforming growth factor beta signaling pathways. Am J Clin Nutr 1998; 68: 1418S–25S
Li D, Yee JA, McGuire MH, et al. Soybean isoflavones reduce experimental metastasis in mice. J Nutr 1999; 129: 1075–78
Li Y, Bhuiyan M, Sarkar FH. Induction of apoptosis and inhibition of c-erbB-2 in MDA-MB-435 cells by genistein. Int J Oncol 1999; 15: 525–33
Schleicher RL, Lamartiniere CA, Zheng M, et al. The inhibitory effect of genistein on the growth and metastasis of a transplantable rat accessory sex gland carcinoma. Cancer Lett 1999; 136: 195–201
Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietaryderived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci U S A 1993; 90: 2690–4
Zhou JR, Gugger ET, Tanaka T, et al. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumour angiogenesis in mice. J Nutr 1999; 129: 1628–35
Peterson TG, Coward L, Kirk M, et al. Isoflavones and breast epithelial cell growth: the importance of genistein and biochanin A metabolism in the breast. Carcinogenesis 1996; 17: 1861–9
Peterson TG, Ji G-P, Kirk M, et al. Metabolism of the isoflavones genistein and biochanin A in human breast cancer cell lines. Am J Clin Nutr 1998; 68: 1505S–11S
Boersma BJ, Patel RP, Kir M, et al. Chlorination and nitration of soy isoflavones. Arch Bio chem Biophys 1999; 368: 265–75
Brown M. Estrogen receptor molecular biology. Hematol Oncol Clin North Am 1994; 8: 101–12
Barnes S, Kim H, Darley-Usmar V, et al. Beyond ERα and ERβ: estrogen receptor binding is only part of the isoflavone story. J Nutr 2000; 130: 656S–7S
Lee HP, Gourley L, Duggu SW, et al. Dietary effects on breast cancer risk in Singapore. Lancet 1991; 337: 1197–1200
Yuan JM, Wang QS, Ross RK, et al. Diet and breast cancer in Shanghai and Tianjin, China Br J Cancer 1995; 71: 1353–8
Zheng W, Dai Q, Custer LJ, et al. Urinary excretion of isoflavonoids and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 1999; 8: 35–40
McMichael Phillips DF, Harding C, Morton M, et al. Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. Am J Clin Nutr 1998; 68: 1431S–5S
Hargreaves DF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab 1999; 84: 4017–24
Ingram D, Sanders K, Kolybaba M, et al. Case-control study of phyto-oestrogens and breast cancer. Lancet 1997; 350: 990–4
Finkel E. Phyto-oestrogens: the way to postmenopausal health? [editorial]. Lancet 1998; 352: 1762
Goodman MT, Wilkens LR, Hankin JH, et al. Association of soy and fibre consumption with the risk of endometrial cancer. Am J Epidemiol 1997; 146: 294–306
Cline JM, Paschold JC, Anthony MS, et al. Effects of hormonal therapies and dietary soy phytoestrogens on vaginal cytology in surgically postmenopausal macaques. Fertil Steril 1996; 65: 1031–5
Tansey G, Hughes Jr CL, Cline JM, et al. Effects of dietary soybean estrogens on the reproductive tract in female rats. Proc Soc Exp Biol Med 1998; 217: 340–4
Foth D, Cline JM. Effects of mammalian and plant estrogens on mammary glands and uteri of macaques. Am J Clin Nutr 1998; 68: 1413S–7S
Cohen LA, Zhao Z, Pittman B, et al. Effect of intact and isoflavone-depleted soy protein on NMU-induced rat mammary tumourigenesis. Carginogenesis 2000; 21: 929–35
Petrakis NL, Barnes S, King EB, et al. Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women. Cancer Epidemiol Biomark Prev 1996; 5: 785–94
Lu L-JW, Anderson KE, Grady JJ, et al. Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction. Cancer Epidemiol Biomark Prev 1996; 5: 63–70
Nagata C, Takatsuka N, Inaba S, et al. Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women. J Natl Cancer Inst 1998; 90: 1830–5
Duncan AM, Merz BE, Xu X, et al. Soy isoflavones exert modest effects in premenopausal women. J Clin Endocrinol Metab 1999; 84: 192–7
Cassidy A, Bingham S, Setchell K. Biological effects of isoflavones in young women: importance of the chemical composition of soyabean products. Br J Nutr 1995; 74: 587–601
Messina JM. Legumes and soybeans: Overview of their nutritional profiles and health effects. Am J Clin Nutr 1999; 70: 439S–50S
Bouker KB, HilakiviClarke L. Genistein: does it prevent or promote breast cancer? Envinron Health Perspect 2000; 108: 701–9
Oishi K, Okada K, Yoshida O, et al. A case-control study of prostatic cancer with reference to dietary habits. Prostate 1988; 12: 179–90
Mills PK, Beeson WL, Phillips RL, et al. Cohort study of diet, lifestyle and prostate cancer in Adventist men. Cancer 1989; 64: 598–604
Severson RK, Nomura AMY, Grove S, et al. A prospective study of demographics and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res 1989; 49: 1857–60
Adlercreutz CHT, Goldin BR, Gorbach SL, et al. Soybean phytoestrogen intake and cancer risk. J Nutr 1995; 125: 757S–70S
Kondo K, Tsuneizumi K, Watanabe T, et al. Induction of in vitro differentiation of mouse embryonal carcinoma (F9) cells by inhibitors of topoisomerases. Cancer Res 1991; 51: 5398–404
Adlercreutz H. Phytoestrogens: epidemiology and a possible role in cancer protection. Environ Health Perspect 1995; 103: 103–12
Urban D, Irwin W, Kirk M, et al. The effect of isolated soy protein on-plasma biomarkers in elderly men with elevated serum prostate specific antigen. J Urol 2001; 165: 294–300
Stephens FO. Phytoestrogens and prostate cancer: possible preventive role. Med J Aust 1997; 167: 138
Peterson G, Barnes S. Genistein and biochanin-A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation. Prostate 1993; 22: 335–45
Adlercreutz H, Mazur W, Bartels P, et al. Phyto-oestrogen and prostate disease. J Nutr 2000; 130: 658S–9S
Mäkelä SI, Pylkkänen LH, Santti RS, Adlercreutz H. Dietary soybean may be antiestrogenic in male mice. J Nutr 1995; 125: 437–45
Evans BAJ, Griffiths K, Morton MS. Inhibition of 5-α reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. J Endocrinol 1995; 147: 295–302
Potter SM, Baum JA, Teng HY, et al. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998; 1375S–9S
Wangen KE, Duncan AM, Merz-Demlow BE, et al. Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrinol Metab 2000; 85: 3043–8
Arjmandi BH, Birbaum R, Goyal NV, et al. Bone sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content. Am J Clin Nutr 1998; 68: 1364S–68S
Jayo MJ, Anthony MS, Registe TC et al. Dietary soy isoflavones and bone loss in ovariectomized monkeys [abstract]. FASEB J 1997; 11: S228
Somekawa Y, Chiguchi M, Ishibashi T, et al. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol 2001; 97: 109–15
Kardinaal AF, Morton MS, Bruggemann Rotgans IE, et al. Phyto-oestrogen excretion and rate of bone loss in postmenopausal women. Eur J Clin Nutr 1998; 52: 850–5
Burke GL, Vitolins MZ, Bland D. Soybean isoflavones as an alternative to traditional hormone replacement therapy: are we there yet? J Nutr 2000; 130: 664S–5S
Manolio TA, Furberg CD, Shemanski L, et al. Associations of postmenopausal estrogen use with cardiovascular disease and its risk factors in older women. The CHS Collaborative Research Group. Circulation 1993; 88: 2163–71
Nabulsi AA, Folsom AR, White A, et al. Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. The Atherosclerosis Risk in Communities Study Investigators. N Engl J Med 1993; 328: 1069–75
Brzezinski A, Adlercreutz H, Shaoul R, et al. Short term effects of phytoestrogens-rich diet on postmenopausal women. Menopause 1997; 4: 89–94
Duncan AM, Underhill KEW, X X, et al. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab 1999: 84: 3479–84
Kurzer MS. Hormonal effects of soy isoflavones: studies in premenopausal and postmenopausal women. J Nutr 2000; 130: 660S–1S
Murkies AL, Lombard C, Strauss BJG, et al. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas 1995; 21: 189–95
Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol 1998; 91: 6–11
Quella SK, Loprinzi CL, Barton DL, et al. Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial. J Clin Oncol 2000; 18: 1068–74
Baird DD, Umbach DM, Lansdell L, et al. Dietary intervention study to assess estrogenicity of dietary soy among post-menopausal women. J Clin Endocrinol Metab 1995; 80: 1685–90
Cline JM, Hughes Jr CL, Phytochemicals for the prevention of breast and endometrial cancer. Cancer Treat Res 1998; 94: 107–34
Vincent A, Fitzpatrick LA. Soy isoflavones: are they useful in menopause? Mayo Clinic Proceedings 2000; 75: 1174–84
Anonymous. The role of isoflavones in menopausal health-Consensus opinion of The North American Menopause Society. Menopause 2000; 7: 215—29
Barrett-Connor E, Grady D. Hormone replacement therapy, heart disease, and other considerations. Annu Rev Public Health 1998; 19: 55–72
Yaffe K, Grady D, Pressman A, et al. Serum estrogen levels, cognitive performance, and risk of cognitive decline in older community women. J Am Geriatr Soc 1998; 46: 816–21
Yaffe K, Sawaya G, Grady D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA 1998; 279: 688–95
White L, Petrovitch H, Ross GW, et al. Association of mid-life consumption of tofu with late life cognitive impairment and dementia: the Honolulu-Asia Aging Study [abstract]. Neurobiol Aging 1996 17: 5121
Pan Y, Anthony M, Clarkson TB. Effect of estradiol and soy phytoestrogens on choline acetyltransferase and nerve growth factor mRNAs in the frontal cortex and hippocampus of female rats. Proc Soc Exp Biol Med 1999; 221: 118–25
Mulnard RA, Cotman CW, Kawas C, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomised controlled trial. Alzheimer’s Disease Cooperative Study. JAMA 2000; 283: 1007–15
White LR, Petrovitch H, Ross GW, et al. Brain aging and midlife tofu consumption. J Am Coll Nutr 2000; 19: 242–558
Kulling SE, Metzler M. Induction of micronuclei, DNA strand breaks and HPRT mutations in cultured Chinese hamster V79 cells by the phytoestrogen coumoestrol. Food Chem Toxicol 1997; 35: 605–13
Kulling SE, Rosenberg B, Jacobs E, et al. The phytoestrogen coumoestrol and genistein induce structural chromosomal aberrations in cultured human peripheral blood lymphocytes. Arch Toxicol 1999; 73: 50–4
Kaufmann WK. Human topoisomerase II function, tyrosine phosphorylation and cell cycle checkpoints. Proc Soc Exp Biol Med 1998; 217: 327–34
Reinhart KC, Dubey RK, Keller PJ, et al. Xeno-oestrogens and phyto-oestrogens induce the synthesis of leukaemia inhibitory factor by human and bovine oviduct cells. Mol Hum Reprod 1999; 10: 899–907
Abe T. Infantile leukaemia and soybeans: a hypothesis. Leukaemia 1999; 13: 317–20
Plewa MJ, Wagner ED, Berhow MA, et al. Antimutagenic activity of chemical fractions isolated from a commercial soybean processin by-product. Teratogenesis, Carcinogenesis, and Mutagenesis 1999; 19: 121–35
McCabe Jr MJ, Orrenius S. Genistein induces apoptosis in immature human thymocytes by inhibiting topoisomerase II. Biochem Biophys Res Commun 1993. 194: 944–50
Traganos F, Ardelt B, Halko N, et al. Effects of genistein of the growth and cell cycle progression of normal human lymphocytes and human leukaemicMOLT-4 andHL-60 cells. Cancer Res 1992; 6200–8
Kumi-Diaka J, Rodrigue R, Doudazi G. Influence of genistein (4′,5,7-thrihydroxyisoflavone) on the growth and proliferation of testicular cell lines. Biol Cell 1998; 90: 349–54
Kumi-Diaka J, Ngguyen V, Butler A. Cytotoxic potential of the phytochemical genistein isoflavone (4′,5′,7-trihydroxyisoflavone) and certain environmental chemical compounds on testicular cells. Biol Cell 1999; 91: 515–23
Fort P, Moses N, Fasano M, et al. Breast and soy-formula feedings in early infancy and the prevalence of autoimmune thyroid disease in children. J Am Coll Nutr 1990: 9: 164–7
Divi RL, Chang HC, Doerge DR. Anti-thyroid isoflavones from soybean. Biochem Pharmacol 1997; 54: 1087–96
Stocker R. Dietary and pharmacological antioxidants in atherosclerosis. Curr Opin Lipidol 1999; 10: 589–97
Blakely JA. The Heart and Estrogen/Progestin Replacement Study revisited: hormone replacement therapy produced net harm, consistent with the observational data. Arch Intern Med 2000; 160: 2897–900
Ginsburg J, Prelevic GM. Lack of significant hormonal effects and controlled trials of phyto-oestrogen. Lancet 2000; 355: 163–4
Sirtori CR. Dubious benefits and potential risk of soy phytooestrogens. Lancet 2000; 355: 849
Impiego di Citrus aurantium, Hypericum perforatum e di Isoflavoni nel settore alimentare. Circular Letter. Rome: Ministero della Sanità, 1999 Oct 20 (600.12/AG45.1/2688)
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This work was supported in part by The Consiglio Nazionale delle Ricerche of Italy (Progetto: Proprietà Chimico Fisiche dei Medicamenti e loro Sicurezza d’Uso) and by the Ministero dell’Università e della Ricerca Scientifica e Tecnologica, Italy.
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Sirtori, C.R. Risks and Benefits of Soy Phytoestrogens in Cardiovascular Diseases, Cancer, Climacteric Symptoms and Osteoporosis. Drug-Safety 24, 665–682 (2001). https://doi.org/10.2165/00002018-200124090-00003
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DOI: https://doi.org/10.2165/00002018-200124090-00003