Phytoestrogens: End of a tale?

Annals of Medicine

Volumn 37, Issue 6, 2005, Pages 423-438

  Sirtori, Cesare R ^a   Arnoldi, Anna ^a   Johnson, Stuart K ^b  

^a UNIVERSITY OF MILAN   (Italy)

^b DEAKIN UNIVERSITY   (Australia)

Author keywords

Atherosclerosis; Isoflavones; Menopause; Osteoporosis; Phytoestrogens; Regulatory issues; Soy; Toxicity

Indexed keywords

DAIDZEIN; GENISTEIN; GLYCITEIN; IPRIFLAVONE; LIPOPROTEIN; PHYTOESTROGEN;

ANGIOGENESIS; ATHEROSCLEROSIS; BIOLOGICAL ACTIVITY; BONE TURNOVER; BREAST CANCER; CANCER INCIDENCE; CARDIOVASCULAR RISK; CARDIOVASCULAR SYSTEM; CELL DIFFERENTIATION; CELL PROLIFERATION; CLINICAL TRIAL; DRUG MEGADOSE; DRUG METABOLISM; DRUG STRUCTURE; HORMONE METABOLISM; HORMONE SYNTHESIS; HUMAN; MENOPAUSAL SYNDROME; META ANALYSIS; NONHUMAN; OSTEOPOROSIS; OXIDATION; PRIORITY JOURNAL; PROSTATE CANCER; SHORT SURVEY; SYSTEMATIC REVIEW; VASODILATATION;

BREAST NEOPLASMS; CARDIOVASCULAR SYSTEM; FEMALE; HUMANS; MALE; PHYTOESTROGENS; PROSTATIC NEOPLASMS;

EID: 26944477010     PISSN: 07853890     EISSN: 16512219     Source Type: Journal    
DOI: 10.1080/07853890510044586     Document Type: Short Survey

References (151)

1. Adlercreutz H, Mazur H. Phyto-oestrogens and Western Diseases. Ann Med. 1997;29:95-120.
2. Bennetts HW, Underwood EJ, Shier FL. A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust Vet J. 1946;22:2-12.
3. Cornwell T, Cohick W, Raskin I. Dietary phytoestrogens and health. Phytochemistry. 2004;65:995-1016.
4. Lamikanra O, Grimm CC, Rodin JB, Inyang ID. Hydroxylated stilbenes in selected american wines. J Agric Food Chem. 1996;44:1111-5.
5. Fremont L. Biological effects of resveratrol. Life Sci. 2000;66:663-73.
6. Franke AA, Custer LJ, Cerna CM, Narala KK. Quantitation of phytoestrogens in legumes by HPLC. J Agric Food Chem. 1994;42:1905-13.
7. Setchell KD, Lawson AM, Borriello SP, Harkness R, Gordon H, Morgan DM, et al. Lignan formation in man - microbial involvement and possible roles in relation to cancer. Lancet. 1981;2:4-7.
8. Duncan AM, Phipps WR, Kurzer MS. Phyto-oestrogens. Best Practice Res Clin Endocrinol Metab. 2003;17:253-71.
9. Munro IC, Harwood M, Hlywka JJ, Stephen AM, Doull J, Flamm WG, et al. Soy isoflavones: A safety review. Nutr Rev. 2003;61:1-33.
10. Meyer BJ, Larkin TA, Owen AJ, Astheimer LB, Tapsell LC, Howe PRC. Limited lipid-lowering effects of regular consumption of whole soybean foods. Ann Nutr Metab. 2004;48:67-78.
11. Rowland IR, Wiseman H, Sanders TAB, Adlercreutz H, Bowey EA. Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut microflora. Nutr Cancer. 2000;36: 27-32.
12. Duncan AM, Merz-Demlow BE, Xu X, Phipps WR, Kurzer MS. Premenopausal equol excretors show plasma hormone profiles associated with lowered risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2000;9:581-6.
13. Setchell KDR, Brown NM, Lydeking-Olsen E. The clinical importance of the metabolite equol - a clue to the effectiveness of soy and its isoflavones. J Nutr. 2002; 132: 3577-84.
14. Nagata C, Kabuto M, Kurisu Y, Shimizu H. Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women. Nutr Cancer. 1997;29:228-33.
15. Chen Z, Zheng W, Custer LJ, Dai Q, Shu XO, Jin F, et al. Usual dietary consumption of soy foods and its correlation with the excretion rate of isoflavonoids in overnight urine samples among Chinese women in Shanghai. Nutr Cancer. 1999;33:82-7.
16. Horn-Ross PL, John EM, Lee M, Stewart SL, Koo J, Sakoda LC, et al. Phytoestrogen consumption and breast cancer risk in a multiethnic population: the Bay Area Breast Cancer Study. Am J Epidemiol. 2001;154:434-41.
17. Kiely M, Faughnan M, Wähälä K, Brandts H, Mulligan A. Phyto-oestrogen levels in foods: the design and construction of the VENUS database. Br J Nutr. 2003;89:808-13.
18. Van Erp-Baart MAJ, Brants HAM, Kiely M. Isoflavone intake in four different European countries: the VENUS approach. Br J Nutr. 2003;89:25-30.
19. FDA Food labeling health claims, soybean protein and coronary heart disease. Food and Drug Administration. Final rule. Federal Register. 1999;64:57699-733.
20. Sirtori CR, Lovati MR. Soy proteins and cardiovascular disease. Curr Atheroscl Rep. 2001;3:47-53.
21. Sirtori CR, Pazzucconi F, Colombo L, Battistin P, Bondioli A, Descheemaeker K. Double-blind study of the addition of high-protein soya milk v. cow's milk to the diet of patients with severe hypercholesterolaemia and resistance to or intolerance of statins. Br J Nutr. 1999;82:91-6.
22. de Kleijn MJ, van der Schouw YT, Wilson PW, Grobbee DE, Jacques PF. Dietary intake of phytoestrogens is associated with a favorable metabolic cardiovascular risk profile in post-menopausal U.S. women: the Framingham study. J Nutr. 2002;132:276-82.
23. 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.
24. Sirtori CR, Agradi E, Conti F, Mantero O, Gatti E. Soybean-protein diet in the treatment of type II hyperlipoproteinaemia. Lancet. 1977;i:275-7.
25. Descovich GC, Ceredi C, Gaddi A, Benassi MS, Mannino G, Colombo L, et al. Multicentre study of soybean protein diet for outpatient hyper-cholesterolaemic patients. Lancet. 1980;ii:709-12.
26. Grouse 3rd JR, Morgan T, Terry JG, Ellis J, Vitolins M, Burke GL. 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.
27. Anthony S, Clarkson TB, Bullock BC, Wagner JD. Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys. Arterioscler Thromb Vasc Biol. 1997;17:2524-31.
28. Greaves KA, Parks JS, Williams JK, Wagner JD. 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.
29. Nestel PJ, Yamashita T, Sasahara T, Pomeroy S, Dart A, Komesaroff P, et al. Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler Thromb Vasc Biol. 1997;17:3392-8.
30. Hodgson JM, Puddey IB, Beilin LJ, Mori TA, Croft KD. Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentrations: a randomized controlled trial in humans. J Nutr. 1998;128:728-32.
31. Dewell A, Hollenbeck CB, Bruce B. The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women. J Clin Endocrinol Metab. 2002;87:118-21.
32. Gianazza E, Eberini I, Arnoldi A, Wait R, Sirtori CR. A proteomic investigation of isolated soy proteins with variable effects in experimental and clinical studies. J Nutr. 2003;133:9-14.
33. Fukui K, Tachibana N, Wanezaki S, Tsuzaki S, Takamatsu K, Yamamoto T, et al. Isoflavone-free soy protein prepared by column chromatography reduces plasma cholesterol in rats. J Agr Food Chem. 2002;50: 5717-21.
34. Anderson JW. Diet first, then medication for hypercholesterolemia. JAMA. 2003;290:531-3.
35. Lovati MR, Manzoni C, Corsini A, Granata A, Frattini R, Fumagalli R, et al. Low density lipoprotein receptor activity is modulated by soybean globulins in cell culture. J Nutr. 1992;122:1971-8.
36. Lovati MR, Manzoni C, Gianazza E, Sirtori CR. Soybean protein products as regulators of liver low-density lipoprotein receptors. I. Identification of active β-conglycinin subunits. J Agric Food Chem. 1998;46:2474-80.
37. Manzoni C, Lovati MR, Gianazza E, Sirtori CR. Soybean protein products as regulators of liver low-density lipoprotein receptors. II. α-α' rich commercial soy concentrate and α' deficient mutant differently affect low-density lipoprotein receptor activation. J Agric Food Chem. 1998;46:2481-4.
38. Lovati MR, Manzoni C, Gianazza E, Arnoldi A, Kurowska E, Carroll KK, et al. Soy protein peptides regulate cholesterol homeostasis in Hep G2 cells. J Nutr. 2000;130:2543-9.
39. Lovati MR, Manzoni C, Canavesi A, Sirtori M, Vaccarino V, Marchi M, et al. Soybean protein diet increases low density lipoprotein receptor activity in mononuclear cells from hypercholesterolemic patients. J Clin Invest. 1987;80: 1498-502.
40. Baum JA, Teng H, Erdman JWJ, Weigel RM, Klein BP, Persky VW, 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.
41. Duranti M, Lovati MR, Dani V, Barbiroli A, Scarafoni A, Castiglioni S, et al. The alpha' subunit from soybean 7S globulin lowers plasma lipids and upregulates liver beta-VLDL receptors in rats fed a hypercholesterolemic diet. J Nutr. 2004;134:1334-9.
42. Erdman JW. Soy protein and cardiovascular disease - A statement for healthcare professionals from the Nutrition Committee of the AHA. Circulation. 2000;102:2555-9.
43. Borradaile NM, de Dreu LE, Wilcox LJ, Edwards JY, Huff MW. Soya phytoestrogens, genistein and daidzein, decrease apolipoprotein B secretion from HepG2 cells through multiple mechanisms. Biochem J. 2002;366:531-9.
44. Walker HA, Dean TS, Sanders TAB, Jackson G, Ritter JM, Chowienczyk PJ. The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17β-estradiol. Circulation. 2001;103:258-62.
45. Squadrito F, Altavilla D, Morabito N, Crisafulli A, D'Anna R, Corrado F, et al. The effect of the phytoestrogen genistein on plasma nitric oxide concentrations, endothelin-1 levels and endothelium dependent vasodilation in postmenopausal women. Atherosclerosis. 2002;163:339-47.
46. Squadrito F, Altavilla D, Crisafulli A, Saitta A, Cucinotta D, Morabito N, et al. Effect of genistein on endothelial function in postmenopausal women: a randomized, double-blind, controlled study. Am J Med. 2003;114:470-6.
47. Simons LA, van Konigsmark M, Simons J, Celermajer DS. Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women. AmJ Cardiol. 2000;85:1297-301.
48. Kreijkamp-Kaspers S, Kok L, Bots ML, Grobbee DE, Lampe JW, van der Schouw YT. Randomized controlled trial of the effects of soy protein containing isofiavones on vascular function in postmenopausal women. Am J Clin Nutr. 2005;81:189-95.
49. Wagner JD, Zhang L, Greaves KA, Shadoan MK, Schwenke DC. 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.
50. Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr. 1997;17:353-81.
51. Wagner JD, Cefalu WT, Anthony MS, Litwak KN, Zhang L, Clarkson TB. 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.
52. Tikkanen MJ, Wahala K, Ojala S, Vihma V, Adlercreutz H. Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance. Proc Natl Acad Sci USA. 1998;95:3106-10.
53. Wiseman H, O'Reilly JD, Adlercreutz H, Mallet AI, Bowey EA, Rowland IR, 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.
54. Samman S, Lyons Wall PM, Chan GS, Smith SJ, Petocz P. The effect of supplementation with isoflavones on plasma lipids and oxidizability of low density lipoprotein in premenopausal women. Atherosclerosis. 1999;147:277-83.
55. Castiglioni S, Manzoni C, D'Uva A, Spiezie R, Monteggia E, Chiesa G, et al. Soy proteins reduce progression of a focal lesion and lipoprotein oxidability in rabbits fed a cholesterol-rich diet. Atherosclerosis. 2003;171:163-70.
56. Vega-Lopez S, Yeum K-J, Lecker JL, Ausman LM, Johnson EJ, Devaray S, et al. Plasma antioxidant capacity in response to diets high in soy or animal protein with or without isoflavones. Am J Clin Nutr. 2005;81:43-9.
57. van der Schouw YT, Kreikamp-Kaspers S, Peeters PHM, Keinan-Boker L, Rimm EB, Grobbee DE. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. Circulation. 2005;111: 465-71.
58. Arora A, Nair MG, Strasburg GM. Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Arch Biochem Biophys. 1998;356:133-41.
59. Chin-Dusting JPF, Boak L, Husband A, Nestel PJ. The isoflavone metabolite dehydroequol produced vasodilation in human resistance arteries via a nitric-oxide dependent mechanism. Atherosclerosis. 2004;176:45-8.
60. Matoba N, Doyama N, Yamada Y, Maruyama N, Utsumi S, Yoshikawa M. Design and production of genetically modified soybean protein with anti-hypertensive activity by incorporating potent analogue of ovokinin(2-7). FEBS Lett. 2001;497:50-4.
61. Sirtori CR, Lovati MR, Manzoni C, Castiglioni S, Duranti M, Magni C, et al. Proteins of white lupin seed, a naturally isoflavone-poor legume, reduce cholesterolemia in rats and increase LDL receptor activity in HepG2 cells. J Nutr. 2004;134:18-23.
62. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology. 1998;139:4252-63.
63. Mäkelä S, Savolainen H, Aavik E, Myllarniemi M, Strauss L, Taskinen E, et al. Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors alpha and beta. Proc Natl Acad Sci U S A. 1999;96:7077-82.
64. Shimokado K, Yokota T, Umezawa K, Sasaguri T, Ogata J. Protein tyrosine kinase inhibitors inhibit chemotaxis of vascular smooth muscle cells. Arterioscler Thromb. 1994;14:973-81.
65. 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.
66. Parkin DM. Cancers of the breast, endometrium and ovary: geographic correlations. Eur J Cancer Clin Oncol. 1989;25:1917-25.
67. Ziegler RG, Hoover RN, Pike MC, Hildesheim A, Nomura AM, West DW, et al. Migration patterns and breast cancer risk in Asian-American women. J Nat Cancer Inst. 1993;85:1819-27.
68. Adlercreutz H, Fotsis T, Heikkinen R, Dwyer JT, Woods M, Goldin BR, et al. Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian post menopausal women and in women with breast cancer. Lancet. 1982;ii:1295-9.
69. Yuan JM, Wang QS, Ross RK, Henderson BE, Yu MC. Diet and breast cancer in Shanghai and Tianjin, China. Br J Cancer. 1995;71:1353-8.
70. Key TJ, Sharp GB, Appleby PN, Beral V, Goodman MT, Soda M, et al. Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan. Br J Cancer. 1999;81:1248-56.
71. Horn-Ross PL, John EM, Lee M, Stewart SL, Koo J, Sakoda LC, et al. Phytoestrogen consumption and breast cancer risk in a multiethnic population: the Bay Area Breast Cancer Study. Am J Epidemiol. 2001;154:434-41.
72. den Tonkelaar I, Keinan-Boker L, Veer PV, Arts CJ, Adlercreutz H, Thijssen JH, et al. Urinary phytoestrogens and postmenopausal breast cancer risk. Cancer Epidemiology, Biomarkers and Prevention. 2001;10:223-8.
73. Ingram D, Sanders K, Kolybaba M, Lopez D. Case-control study of phyto-estrogens and breast cancer. Lancet. 1997;350:990-4.
74. Markiewicz L, Garey J, Adlercreutz H, Gurpide E. In vitro bioassays of non-steroidal phytoestrogens. J Steroid Biochem. 1993;45:399-405.
75. Sathyamoorthy N, Wang TTY. Differential effects of dietary phyto-oestrogens daidzein and equol on human breast cancer MCF-7 cells. Eur J Cancer. 1997;33:2384-9.
76. Krazeisen A, Breitling R, Moller G, Adamski J. Phytoestrogens inhibit human 17beta-hydroxysteroid dehydrogenase type 5. Mol Cell Endocrinol. 2001;171:151-62.
77. Adlercreutz H. Phyto-oestrogens and cancer. Lancet Oncology. 2002;3:364-73.
78. Lamartiniere CA, Cotroneo MS, Fritz WA. Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate. J Nutr. 2002;132:552S-8.
79. Liu B, Edgerton S, Yang X, Kim A, Ordonez-Ercan D, Mason T, Alvarez K, et al. Low-dose dietary phytoestrogen abrogates tamoxifen-associated mammary tumor prevention. Cancer Res. 2005;65:879-86.
80. Pienta KJ, Goodson JA, Esper PS. Epidemiology of prostate cancer: molecular and environmental clues. Urology. 1996;48:676-83.
81. Shimizu H, Ross RK, Bernstein L, Yatani R, Henderson BE, Mack TM. Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer. 1991;63:963-6.
82. Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study (United States). Cancer Causes Control. 1998;9:553-7.
83. Kolonel LN, Hankin JH, Whittemore AS, Wu AH, Gallagher RP, Wilkens LR. Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. Cancer Epidemiol Biomarkers Prev. 2000;9:795-804.
84. Lee MM, Wang RT, Hsing AW, Wang T, Spitz M. Case-control study of diet and prostate cancer in China. Cancer Causes Control. 1998;9:545-52.
85. Oishi K, Okada K, Yoshida O, Yamabe H, Ohno Y, Hayes RB, Schroeder FH. A case-control study of prostatic cancer with reference to dietary habits. Prostate. 1988;12:179-90.
86. Hirayama T. Epidemiology of prostate cancer with special reference to the role of diet. National Cancer Institute Monograph. 1979;53:149-55.
87. Urban D, Irwin W, Kirk M, Markiewicz MA, Myers R, Smith 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.
88. Adams KF, Chen C, Newton KM, Potter JD, Lampe JW. Soy isoflavones do not modulate prostate-specific antigen concentrations in older men in a randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2004;13:644-8.
89. Demark-Wahnefried W, Price DT, Polascik TJ, Robertson CN, Anderson EE, Paulson DF, et al. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology. 2001;58:47-52.
90. Wu AH, Yang D, Pike MC. A meta-analysis of soyfoods and risk of stomach cancer: the problem of potential confounders. Cancer Epidemiol Biomarkers Prev. 2000;9: 1051-8.
91. McKeown-Eyssen GE, Bright-See E. Dietary factors in colon cancer: international relationships. Nutr Cancer. 1984;6:160-70.
92. Tajima K, Tominaga S. Dietary habits and gastro-intestinal cancers: a comparative case-control study of stomach and large intestinal cancers in Nagoya, Japan. Jpn J Cancer Res. 1985;76:705-16.
93. Goodman MT, Wilkens LR, Hankin JH, Lyu LC, Wu AH, Kolonel LN, et al. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiology. 1997;146:294-306.
94. Nelson HD, Humphrey LL, Nygren P, Fanelli M, Venturelli E, Cantatore F, et al. Postmenopausal hormone replacement therapy: scientific review. JAMA. 2002;288: 872-1.
95. Gennari C, Agnusdei D, Crepaldi G, Isaia G, Mazzuoli G, Ortolani S, et al. Effect of ipriflavone - a synthetic derivative of natural isoflavones - on bone mass loss in the early years after menopause. Menopause. 1998;5:9-15.
96. Lauderdale DS, Jacobsen SJ, Furner SE, Levy PS, Brody JA, Goldberg J. Hip fracture incidence among elderly Asian-American populations. Am J Epidemiol. 1997;146:502-9.
97. Tsuchida K, Mizushima S, Toba M, Soda K. Dietary soybeans intake and bone mineral density among 995 middle-aged women in Yokohama. J Epidemiol. 9, 14-9.
98. Kritz-Silverstein D, Goodman-Gruen DL. Usual dietary isoflavone intake, bone mineral density, and bone metabolism in post-menopausal women. J Womens Health Gend Based Med. 2002;11:69-78.
99. Somekawa Y, Chiguchi M, Ishibashi T, Aso T. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol. 2001;97:109-15.
100. Kardinaal AF, Morton MS, Bruggemann Rotgans IE, van Beresteijn EC. Phyto-oestrogen excretion and rate of bone loss in postmenopausal women. Eur J Clin Nutr. 1998;52:850-5.
101. Potter SM, Baum JA, Teng H. Soy protein and iso flavones: their effects on blood lipids and bone density in post-menopausal women. Am J Clin Nutr. 1998;68: 1375S-9.
102. Wangen KE, Duncan AM, Merz-Demlow BE, Xu X, Marcus R, Phipps WR, et al. Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrinol Metab. 2000;85:3043-8.
103. 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-5.
104. Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW, Toda T. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr. 2000;72:844-52.
105. Lydeking-Olsen E, Beck-Jensen J-E, Setchell KDR, Holm-Jensen T. Soymilk or progesterone for prevention of bone loss. A 2 year randomized, placebo-controlled trial. Eur J Nutr. 2004;43:246-57.
106. Chen YM, Ho SC, Lam SS, Ho SS, Woo JL. Beneficial effect of soy isoflavones on bone mineral content was modified by years since menopause, body weight, and calcium intake: a double-blind, randomized, controlled trial. Menopause. 2004;11:246-54.
107. Vitolins M, Anthony M, Lenschik L, Bland Dr, Burke GL. Does soy protein and its isoflavones prevent bone loss in peri- and post-menopausal women? Results of a Two-Year Randomized Clinical Trial. J Nutr. 2002;582S (Abstr).
108. Kreikamp-Kaspers S, Kok L, Grobbee DE, de Haan EHF, Aleman A, Lampe JW, van der Schouw YT. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women. JAMA. 2004;292:65-74.
109. Arjmandi BH, Lucas EA, Khalil DA, Devareddy L, Smith BJ, McDonald J, et al. One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women. Nutr J. 2005;4:8.
110. Spence LA, Lipscomb ER, Cadogan J, Martin B, Wastney ME, Peacocock M, et al. The effect of soy protein and soy isoflavones on calcium metabolism in postmenopausal women: a randomized crossover study. Am J Clin Nutr. 2005;81:916-22.
111. Chiechi L, Secreto G, D'Amore M, Fanelli M, Venturelli E, Cantatore F, et al. Efficacy of a soy rich diet in preventing post-menopausal osteoporosis: the Menfis randomized trial. Maturitas. 2002;42:295-300.
112. Glazier MG, Bowman MA. A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy. Arch Intern Med. 2001;161: 1161-72.
113. Sirtori CR. Risks of benefits of soy phytoestrogens in cardiovascular diseases, cancer, climacteric symptoms and osteoporosis. Drug Safety. 2001;24:665-82.
114. Adlercreutz H, Hamalainen E, Gorbach S, Goldin B. Dietary phyto-oestrogens and the menopause in Japan. Lancet. 1992;339:1233.
115. Nagata C, Takatsuka N, Kawakami N, Shimizu H. Soy product intake and hot flushes in Japanese women: results from a community-based prospective study. Am J Epidemiol. 2001;153:790-3.
116. Yaffe K, Grady D, Pressman A, Cummings S. Serum estrogen levels, cognitive performance, and risk of cognitive decline in older community women. J Am Geriatr Soc. 1998;46:816-21.
117. Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, et al. Women's Health Initiative Memory Study. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA. 2004;291: 2959-68.
118. Hersh AL, Stefanick ML, Stafford RS. National use of postmenopausal hormone therapy: annual trends and response to recent evidence. JAMA. 2004;291:47-53.
119. Murkies AL, Lombard C, Strauss BJG, Wilcox G, Burger HG, Morton MS. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas. 1995;21:189-95.
120. Washburn S, Burke GL, Morgan T, Anthony M. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause. 1999;6:7-13.
121. Duncan AM, Underhill KE, Xu X, Lavalleur J, Phipps WR, Kurzer MS. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab. 1999;84:3479-84.
122. Albertazzi P, Pansini F, Bonaccorsi G, Zanotti L, Forini E, De Aloysio D. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol. 1998;91:6-11.
123. Quella SK, Loprinzi CL, Barton DL, Knost JA, Sloan JA, LaVasseur BI. 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.
124. Van Patten CL, Olivotto IA, Chambers GK, Gelmon KA, Hislop TG, Templeton E, et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol. 2002;20:1449-55.
125. MacGregor CA, Canney PA, Patterson G, McDonald R, Paul J. A randomised double-blind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer. Eur J Cancer. 2005;41:708-14.
126. Washburn S, Burke GL, Morgan T, Anthony M. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause. 1999;6:7-13.
127. Faure ED, Chantre P, Mares P. Effects of a standardized soy extract on hot flushes: a multicenter, double-blind, randomized, placebo-controlled study. Menopause. 2002;9:329-34.
128. Han KK, Soares JM, Jr, Haidar MA, de Lima GR, Baracat EC. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol. 2002;99: 389-94.
129. Colacurci N, Zarcone R, Borrelli A, De Franciscis P, Fortunato N, Cirillo M. Effects of soy isoflavones on menopausal neurovegetative symptoms. Minerva Ginecologica. 2004;56:407-12.
130. Petri Nahas E, Nahas Neto J, De Luca L, Traiman P, Pontes A, Dalben I, et al. Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy. Maturitas. 2004;48: 372-80.
131. Baber RJ, Templeman C, Morton T, Kelly GE. West L. Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric. 1999;2:85-92.
132. Knight DC, Howes JB, Eden JA. The effect of Promensil, an isoflavone extract, on menopausal symptoms. Climacteric. 1999;2:79-84.
133. Kronenberg F, Fugh-Berman A. Complimentary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med. 2002;137: 805-13.
134. Anonymous, The role of isoflavones in menopausal health-consensus opinion of The North American Menopause Society. Menopause. 2000;7:215-29.
135. Setchell KD, Zimmer-Nechemias L, Cai J, Heubi JE. Exposure of infants to phyto-oestrogens from soy-based infant formula. Lancet. 1997;350:23-7.
136. Kulling SE, Rosenberg B, Jacobs E, Metzler M. The phytoestrogens coumoestrol and genistein induce structural chromosomal aberrations in cultured human peripheral blood lymphocytes. Arch Toxicol. l999;73:50-4.
137. Yellayi S, Naaz A, Szewcczykowski M, Sato T, Woods JA, Chang J, et al. The phytoestrogen genistein induces thymic and immmune changes: a human health concern? Proc Natl Acad Sci U S A. 2002;99:7616-21.
138. Sakabe K, Okuma M, Karaki S, Matsuura S, Yoshida T, Aikawa H, et al. Inhibitory effect of natural and environmental estrogens on thymic hormone production in thymus epithelial cell culture. Int J Immunopharmacol. 1999;21: 861-8.
139. Strom BL, Schinnar R, Ziegler EE, Barnhart KT, Sammel MD, Macones GA, et al. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA. 2001;286:807-14.
140. Doerge DR, Sheehan DM. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect. 2002;110:349-53.
141. Chen AC, Berhow MA, Tappenden KA, Donovan SM. Genistein inhibits intestinal cell proliferation in piglets. Pediatr Res. 2005;57:192-200.
142. Chen A, Rogan WJ. Isoflavones in soy infant formula: a review of evidence for endocrine and other activity in infants. Annu Rev Nutr. 2004;24:33-54.
143. Committee on Toxicity of Chemicals in Food Consumer Products the Environment (1996) Annual report of the Committees on Toxicity, Mutagenicity and Carcinogenicity. London: HMSO, 1996: p. 20-2.
144. Agence Française de sécurité sanitaire des aliments, Présentation du rapport sur "Sécurité et bénéfices des phytoestrogènes apportés par l'alimentation Recommandations.
145. Arici A, Bukulmez O. Phyto-oestrogens and the endometrium. Lancet. 2004;364:2081-2.
146. Gazzetta Ufficiale Italiana 18/7/2002, number 188, annex 2.
147. Morandi S, D'Agostina A, Ferrario F, Arnoldi A. Isoflavone content of Italian soy food products and daily intakes of some specific classes of consumers. Eur Food Res Technol. 2005;221:84-91.
148. Kreikamp-Kaspers, Kok L, Bots ML, Grobbee DE, van der Schouw YT. Dietary phytoestrogens and plasma lipids in Dutch postmenopausal women; a cross-sectional study. Atherosclerosis. 2005;178:95-100.
149. Arnoldi A. Grain legumes as a source of food ingredients for the prevention of cardiovascular disease. In: Functional Foods, Diet, Cardiovascular Disease and Diabetes, Arnoldi A. ed. Cambridge, UK: Woodhead Publications Ltd, 2004: p. 422-47.
150. Hall RS, Johnson SK, Baxter AL, Ball MJ. Lupin kernel fibre-enriched foods beneficially modify serum lipids in men. Eur J Clin Nutr. 2005;59:325-33.
151. Martins JM, Riottot M, Abreu MC, Viegas-Crespo AM, Lanca MJ, Almeida JA, et al. Cholesterol-lowering effects of dietary blue lupin seeds (Lupinus angustifolius L.) in intact and ileo-rectal anastomosed growing pigs fed cholesterol-rich diets. J Lipid Res. 2005;46:1539-47.