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Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women

Published online by Cambridge University Press:  07 March 2007

Aedin Cassidy ,
Paola Albertazzi ,
Inge Lise Nielsen ,
Wendy Hall ,
Gary Williamson ,
Inge Tetens ,
Steve Atkins ,
Heide Cross ,
Yannis Manios  and
Alicja Wolk
...Show all authors
Aedin Cassidy*
Affiliation:
School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK
Paola Albertazzi
Affiliation:
Centre for Metabolic Bone Disease, Hull Royal Infirmary, Hull HU3 2RW, UK
Inge Lise Nielsen
Affiliation:
Nestlé Research Center, Vers Chez Les Blanc, Lausanne, Switzerland
Wendy Hall
Affiliation:
School of Food Biosciences, University of Reading, Reading RG6 6AP, UK
Gary Williamson
Affiliation:
Nestlé Research Center, Vers Chez Les Blanc, Lausanne, Switzerland
Inge Tetens
Affiliation:
Department of Nutrition, Institute for Food and Agricultural Research, Søborg, Denmark
Steve Atkins
Affiliation:
Centre for Metabolic Bone Disease, Hull Royal Infirmary, Hull HU3 2RW, UK
Heide Cross
Affiliation:
Department of Pathophysiology, Medical University of Vienna, Vienna, Austria
Yannis Manios
Affiliation:
Department of Nutrition and Dietetics, Harokopio University, Kallithea-Athens, Greece
Alicja Wolk
Affiliation:
The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Claudia Steiner
Affiliation:
Institute of Nutrition, Friedrich-Schiller University of Jena, Jena, Germany
Francesco Branca
Affiliation:
National Institute for Research and Food and Nutrition (INRAS), via Ardeatria 546, 00178 Roma, Italy
*
*Corresponding author: Professor Aedin Cassidy, fax +44 1603 593752, email a.cassidy@uea.ac.uk
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Abstract

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A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

Keywords

GenisteinDaidzeinBioavailabilityBone healthCVD

Information

Type
Symposium on ‘Phytochemicals’
Information
Proceedings of the Nutrition Society , Volume 65 , Issue 1 , February 2006 , pp. 76 - 92
Copyright
Copyright © The Nutrition Society 2006

References

Agency for Health Care Policy and Research (1992) Clinical Practice Guideline for Acute Pain Management: Operative or Medical Procedures and Trauma. AHCPR Publication no. 92–0032. 1st ed. Rockville, MD: Public Health Service, US Department of Health and Human Services.Google Scholar
Albertazzi, P, Pansini, F, Bonaccorsi, G, Zanotti, L, Forini, E, De Aloysio, D (1998) The effect of dietary soy supplementation on hot flushes. Obstetrics and Gynecology 91 6–11.CrossRefGoogle ScholarPubMed
Anderson, JW, Johnstone, BM, Cook-Newell, ME (1995) Meta-analysis of the effects of soy protein intake on serum lipids. New England Journal of Medicine 333 276–282.CrossRefGoogle ScholarPubMed
Atkinson, C, Oosthuizen, W, Scollen, S, Loktionov, A, Day, NE, Bingham, SA (2004 a) Modest protective effects of isoflavones from a red clover-derived dietary supplement on cardiovascular disease risk factors in perimenopausal women, and evidence of an interaction with ApoE genotype in 49–65 year-old women. Journal of Nutrition 134 1759–1764.CrossRefGoogle ScholarPubMed
Atkinson, C, Warren, RM, Sala, E, Dowsett, M, Dunning, AM, Healey, CS, Runswick, S, Day, NE, Bingham, SA (2004 b) Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial. Breast Cancer Research 6 R170–R179.CrossRefGoogle ScholarPubMed
Baber, RJ, Templeman, C, Morton, T, Kelly, GE & West, L (1999) Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric 2 85–92.CrossRefGoogle ScholarPubMed
Bibbins-Domingo, K, Lin, F, Vittinghoff, E, Barrett-Connor, E, Hulley, SB, Grady, D & Shlipak, MG (2004) Predictors of heart failure among women with coronary disease. Circulation 110 1424–1430.CrossRefGoogle ScholarPubMed
Blum, A, Lang, N, Peleg, A, Vigder, F, Israeli, P, Gumanovsky, M, Lupovitz, S, Elgazi, A, Ben-Ami, M (2003 a) Effects of oral soy protein on markers of inflammation in postmenopausal women with mild hypercholesterolemia. American Heart Journal 145 e7CrossRefGoogle Scholar
Blum, A, Lang, N, Vigder, F, Israeli, P, Gumanovsky, M, Lupovitz, S, Elgazi, A, Peleg, A, Ben-Ami, M (2003 b) Effects of soy protein on endothelium-dependent vasodilatation and lipid profile in postmenopausal women with mild hypercholesterolemia. Clinical and Investigative Medicine 26 20–26.Google ScholarPubMed
Bosetti, C, Spertini, L, Parpinel, M, Gnagnarella, P, Lagiou, P, Negri, E et al. (2005) Flavonoids and breast cancer risk in Italy. Cancer Epidemiology, Biomarkers & Prevention 14 805–808.CrossRefGoogle ScholarPubMed
Campbell, MJ, Woodside, JV, Honour, JW, Morton, MS & Leathem, AJ (2004) Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study. European Journal of Clinical Nutrition 58 173–179.CrossRefGoogle ScholarPubMed
Chandalia, M, Garg, A, Lutjohann, D, von Bergmann, K, Grundy, SM & Brinkley, LJ (2000) Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. New England Journal of Medicine 342 1392–1398.CrossRefGoogle ScholarPubMed
Chen, YM, Ho, SC, Lam, SS, Ho, SS & Woo, JL (2003) Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. Journal of Clinical Endocrinology and Metabolism 88 4740–4747.CrossRefGoogle Scholar
Clifton-Bligh, PB, Baber, RJ, Fulcher, GR, Nery, ML & Moreton, T (2001) The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause 8 259–265.CrossRefGoogle ScholarPubMed
Collins, R, Armitage, J, Parish, S, Sleigh, P & Peto, R (2003) MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 361 2005–2016.Google ScholarPubMed
Crisafulli, A, Marini, H, Bitto, A, Altavilla, D, Squadrito, G, Romeo, A et al. (2004) Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT- and placebo-controlled study. Menopause 11 400–404.CrossRefGoogle ScholarPubMed
Cuevas, AM, Irribarra, VL, Castillo, OA, Yanez, MD & Germain, AM (2003) Isolated soy protein improves endothelial function in postmenopausal hypercholesterolemic women. European Journal of Clinical Nutrition 57 889–894.CrossRefGoogle ScholarPubMed
Dai, Q, Franke, AA, Jin, F, Shu, XO, Hebert, JR, Custer, LJ, Cheng, J, Gao, YT & Zheng, W (2002) Urinary excretion of phytoestrogens and risk of breast cancer among Chinese women in Shanghai. Cancer Epidemiology, Biomarkers & Prevention 11 815–821.Google ScholarPubMed
Day, AJ, Canada, FJ, Diaz, JC, Kroon, PA, McLauchlan, R, Faulds, CB, Plumb, GW, Morgan, MR & Williamson, G (2000) Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Letters 468 166–170.CrossRefGoogle ScholarPubMed
den Tonkelaar, I, Keinan-Boker, L, Veer, PV, Arts, CJ, Adlercreutz, H, Thijssen, JH & Peeters, PH (2001) Urinary phytoestrogens and postmenopausal breast cancer risk. Cancer Epidemiology, Biomarkers & Prevention 10 223–228.Google ScholarPubMed
Desroches, S, Mauger, JF, Ausman, LM, Lichtenstein, AH & Lamarche, B (2004) Soy protein favorably affects LDL size independently of isoflavones in hypercholesterolemic men and women. Journal of Nutrition 134 574–579.CrossRefGoogle ScholarPubMed
Dewell, A, Hollenbeck, CB & Bruce, B (2002) The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women. Journal of Clinical Endocrinology and Metabolism 87 118–121.CrossRefGoogle ScholarPubMed
Eisen, B, Ungar, Y & Shimoni, E (2003) Stability of isoflavones in soy milk stored at elevated and ambient temperatures. Journal of Agricultural and Food Chemistry 51 2212–2215.CrossRefGoogle ScholarPubMed
Faughnan, MS, Hawdon, A, Ah-Singh, E, Brown, J, Millward, DJ & Cassidy, A (2004) Urinary isoflavone kinetics: the effect of age, gender, food matrix and chemical composition. British Journal of Nutrition 91 567–574.CrossRefGoogle ScholarPubMed
Faure, ED, Chantre, P & Mares, P (2002) Effects of a standardized soy extract on hot flushes: a multicenter, double-blind, randomized, placebo-controlled study. Menopause 9 329–334.CrossRefGoogle ScholarPubMed
Gallagher, JC, Satpathy, R, Rafferty, K & Haynatzka, V (2004) The effect of soy protein isolate on bone metabolism. Menopause 11 290–298.CrossRefGoogle ScholarPubMed
Gardner, CD, Newell, KA, Cherin, R & Haskell, WL (2001) The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. American Journal of Clinical Nutrition 73 728–735.CrossRefGoogle ScholarPubMed
Grace, PB, Taylor, JI, Low, YL, Luben, RN, Mulligan, AA, Botting, NP et al. (2004) 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 cancer and nutrition-norfolk. Cancer Epidemiology, Biomarkers & Prevention 13 698–708.CrossRefGoogle ScholarPubMed
Greene, JG (1998) Constructing a standard climacteric scale. Maturitas 29 25–31.CrossRefGoogle ScholarPubMed
Haenszel, W, Berg, JW, Segi, M, Kurihara, M & Locke, FB (1973) Large-bowel cancer in Hawaiian Japanese. Journal of the National Cancer Institute 51 1765–1779.CrossRefGoogle ScholarPubMed
Hall, WL, Vafeiadou, K, Minihane, AM, Williams, CM & Rimbach, GH (2004) Isoflavones and coronary heart disease. In Functional Foods, Cardiovascular Disease and Diabetes, pp. 187–214 [Arnoldi, A, editor]. Cambridge: Woodhead Publishing Ltd.CrossRefGoogle Scholar
Hall, WL, Vafeiadou, K, Hallund, J, Bugel, S, Koebnick, C, Reimann, M et al. (2005) Soy isoflavone enriched foods and inflammatory biomarkers of cardiovascular risk in post-menopausal women: interactions with genotype and equol production. American Journal of Clinical Nutrition (In the Press).CrossRefGoogle Scholar
Han, KK, Soares, JM Jr, Haidar, MA, de Lima, GR & Baracat, EC (2002) Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstetrics and Gynecology 99 389–394.Google ScholarPubMed
Harbour, R & Miller, J (2001) A new system for grading recommendations in evidence based guidelines. British Medical Journal 323 334–336.CrossRefGoogle ScholarPubMed
Hermansen, K, Sondergaard, M, Hoie, L, Carstensen, M & Brock, B (2001) Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects. Diabetes Care 24 228–233.CrossRefGoogle ScholarPubMed
Hirayama, T (1990) Life-style and Mortality. A Large-scale Census-based Cohort Study in Japan. Basel, Switzerland: Karger.Google Scholar
Hirose, K, Tajima, K, Hamajima, N, Inoue, M, Takezaki, T, Kuroishi, T, Yoshida, M & Tokudome, S (1995) A large-scale, hospital-based case-control study of risk factors of breast cancer according to menopausal status. Japanese Journal of Cancer Research 86 146–154.CrossRefGoogle ScholarPubMed
Hodgson, JM, Puddey, IB, Beilin, LJ, Mori, TA, Burke, V, Croft, KD, Rogers, PB (1999 a) Effects of isoflavonoids on blood pressure in subjects with high-normal ambulatory blood pressure levels: a randomized controlled trial. American Journal of Hypertension 12 47–53.CrossRefGoogle ScholarPubMed
Hodgson, JM, Puddey, IB, Beilin, LJ, Mori, TA & Croft, KD (1998) Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentrations: a randomized controlled trial in humans. Journal of Nutrition 128 728–732.CrossRefGoogle Scholar
Hodgson, JM, Puddey, IB, Croft, KD, Mori, TA, Rivera, J & Beilin, LJ (1999 b) Isoflavonoids do not inhibit in vivo lipid peroxidation in subjects with high–normal blood pressure. Atherosclerosis 145 167–172.CrossRefGoogle Scholar
Hoshiyama, Y, Sekine, T & Sasaba, T (1993) A case-control study of colorectal cancer and its relation to diet, cigarettes, and alcohol consumption in Saitama Prefecture, Japan. Tohoku Journal of Experimental Medicine 171 153–165.CrossRefGoogle ScholarPubMed
Howes, JB, Bray, K, Lorenz, L, Smerdely, P & Howes, LG (2004) The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women. Climacteric 7 70–77.CrossRefGoogle ScholarPubMed
Howes, JB, Sullivan, D, Lai, N, Nestel, P, Pomeroy, S, West, L, Eden, JA & Howes, LG (2000) The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia. Atherosclerosis 152 143–147.CrossRefGoogle ScholarPubMed
Howes, JB, Tran, D, Brillante, D & Howes, LG (2003) Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes. Diabetes Obesity & Metabolism 5 325–332.CrossRefGoogle ScholarPubMed
Hu, FB, Manson, JE, Stampfer, MJ, Colditz, G, Liu, S, Solomon, CG & Willett, WC (2001) Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. New England Journal of Medicine 345 790–797.CrossRefGoogle ScholarPubMed
Hu, JF, Liu, YY, Yu, YK, Zhao, TZ, Liu, SD & Wang, QQ (1991) Diet and cancer of the colon and rectum: a case-control study in China. International Journal of Epidemiology 20 362–367.CrossRefGoogle ScholarPubMed
Huntley, AL & Ernst, E (2003) A systematic review of herbal medicinal products for the treatment of menopausal symptoms. Menopause 10 465–476.CrossRefGoogle ScholarPubMed
Huntley, AL & Ernst, E (2004) Soy for the treatment of perimenopausal symptoms – a systematic review. Maturitas 47 1–9.CrossRefGoogle ScholarPubMed
Ingram, D, Sanders, K, Kolybaba, M & Lopez, D (1997) Case-control study of phyto-oestrogens and breast cancer. Lancet 350 990–994.CrossRefGoogle ScholarPubMed
Izumi, T, Piskula, MK, Osawa, S, Obata, A, Tobe, K, Saito, M, Kataoka, S, Kubota, Y & Kikuchi, M (2000) Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. Journal of Nutrition 130 1695–1699.CrossRefGoogle ScholarPubMed
Jadad, AR, Moore, RA, Carroll, D, Jenkinson, C, Reynolds, DJ, Gavaghan, DJ & McQuay, HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary. Controlled Clinical Trials 17 1–12.CrossRefGoogle ScholarPubMed
Jakes, RW, Duffy, SW, Ng, FC, Gao, F, Ng, EH, Seow, A, Lee, HP & Yu, MC (2002) Mammographic parenchymal patterns and self-reported soy intake in Singapore Chinese women. Cancer Epidemiology, Biomarkers & Prevention 11 608–613.Google ScholarPubMed
Jayagopal, V, Albertazzi, P, Kilpatrick, ES, Howarth, EM, Jennings, PE, Hepburn, DA & Atkin, SL (2002) Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes. Diabetes Care 25 1709–1714.CrossRefGoogle ScholarPubMed
Jenkins, DJ, Kendall, CW, Connelly, PW, Jackson, CJ, Parker, T, Faulkner, D & Vidgen, E (2002) Effects of high- and low-isoflavone (phytoestrogen) soy foods on inflammatory biomarkers and proinflammatory cytokines in middle-aged men and women. Metabolism 51 919–924.CrossRefGoogle ScholarPubMed
Keinan-Boker, L, van Der Schouw, YT, Grobbee, DE & Peeters, PH (2004) Dietary phytoestrogens and breast cancer risk. American Journal of Clinical Nutrition 79 282–288.CrossRefGoogle ScholarPubMed
King, RA & Bursill, DB (1998) Plasma and urinary kinetics of the isoflavones daidzein and genistein after a single soy meal in humans. American Journal of Clinical Nutrition 67 867–872.CrossRefGoogle ScholarPubMed
Knight, DC, Howes, JB & Eden, JA (1999) The effect of Promensil, an isoflavone extract, on menopausal symptoms. Climacteric 2 79–84.CrossRefGoogle ScholarPubMed
Knight, DC, Howes, JB, Eden, JA & Howes, LG (2001) Effects on menopausal symptoms and acceptability of isoflavones-containing soy powder dietary supplementation. Climacteric 4 13–18.CrossRefGoogle Scholar
Kono, S, Imanishi, K, Shinchi, K & Yanai, F (1993) Relationship of diet to small and large adenomas of the sigmoid colon. Japanese Journal of Cancer Research 84 13–19.CrossRefGoogle ScholarPubMed
Kotsopoulos, D, Dalais, FS, Liang, YL, McGrath, BP & Teede, HJ (2000) The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. Climacteric 3 161–167.CrossRefGoogle ScholarPubMed
Krebs, EE, Ensrud, KE, MacDonald, R & Wilt, TJ (2004) Phytoestrogens for treatment of menopausal symptoms: a systematic review. Obstetrics and Gynecology 104 824–836.CrossRefGoogle ScholarPubMed
Kreijkamp-Kaspers, S, Kok, L, Grobbee, DE, de Haan, EH, Aleman, A, Lampe, JW, van der Schouw, YT (2004) Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. Journal of the American Medical Association 292 65–74.Google ScholarPubMed
Kritz-Silverstein, D, Von Muhlen, D, Barrett-Connor, E & Bressel, MA (2003) Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study. Menopause 10 196–202.CrossRefGoogle ScholarPubMed
Kupperman, HS, Blatt, M, Wiesbader, H & Filler, W (1953) Comparative clinical evaluation of estrogenic preparations by the menopausal and amenorrheal indices. Journal of Clinical Endocrinology and Metabolism 13 688–703.CrossRefGoogle ScholarPubMed
Lampe, JW, Karr, SC, Hutchins, AM & Slavin, JL (1998) Urinary equol excretion with a soy challenge: influence of habitual diet. Proceedings of the Society for Experimental Biology and Medicine 217 335–339.CrossRefGoogle ScholarPubMed
Le Marchand, L, Hankin, JH, Wilkens, LR, Kolonel, LN, Englyst, HN & Lyu, LC (1997) Dietary fiber and colorectal cancer risk. Epidemiology 8 658–665.CrossRefGoogle ScholarPubMed
Lee, HP, Gourley, L, Duffy, SW, Esteve, J, Lee, J & Day, NE (1991) Dietary effects on breast-cancer risk in Singapore. Lancet 337 1197–1200.CrossRefGoogle ScholarPubMed
Lee, SJ, Ahn, JK, Kim, SH, Kim, JT, Han, SJ, Jung, MY & Chung, IM (2003) Variation in isoflavone of soybean cultivars with location and storage duration. Journal of Agricultural and Food Chemistry 51 3382–3389.CrossRefGoogle ScholarPubMed
Li, Z, Hong, K, Saltsman, P, DeShields, S, Bellman, M, Thames, G, Liu, Y, Wang, HJ, Elashoff, R & Heber, D (2005) Long-term efficacy of soy-based meal replacements vs an individualized diet plan in obese type II DM patients: relative effects on weight loss, metabolic parameters, and C-reactive protein. European Journal of Clinical Nutrition 59 411–418.CrossRefGoogle ScholarPubMed
Lichtenstein, AH, Jalbert, SM, Adlercreutz, H, Goldin, BR, Rasmussen, H, Schaefer, EJ & Ausman, LM (2002) Lipoprotein response to diets high in soy or animal protein with and without isoflavones in moderately hypercholesterolemic subjects. Arteriosclerosis, Thrombosis, and Vascular Biology 22 1852–1858.CrossRefGoogle ScholarPubMed
Linseisen, J, Piller, R, Hermann, S, Chang-Claude, J (2004) Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study. International Journal of Cancer 110 284–290.CrossRefGoogle Scholar
Lissin, LW, Oka, R, Lakshmi, S & Cooke, JP (2004) Isoflavones improve vascular reactivity in post-menopausal women with hypercholesterolemia. Vascular Medicine 9 26–30.CrossRefGoogle ScholarPubMed
Lock, M (1993) Encounters with Ageing. Mythology of Menopause in Japan and North America. Oakland, CA: University of California Press.Google Scholar
Lu, LJ & Anderson, KE (1998) Sex and long-term soy diets affect the metabolism and excretion of soy isoflavones in humans. American Journal of Clinical Nutrition 68 1500S–1504S.CrossRefGoogle Scholar
Mackey, R, Ekangaki, A & Eden, JA (2000) The effects of soy protein in women and men with elevated plasma lipids. Biofactors 12 251–257.CrossRefGoogle ScholarPubMed
Mahungu, SM, Diaz-Mercado, S, Li, J, Schwenk, M, Singletary, K & Faller, J (1999) Stability of isoflavones during extrusion processing of corn/soy mixture. Journal of Agricultural and Food Chemistry 47 279–284.CrossRefGoogle ScholarPubMed
Maskarinec, G, Franke, AA, Williams, AE, Hebshi, S, Oshiro, C, Murphy, S & Stanczyk, FZ (2004) Effects of a 2-year randomized soy intervention on sex hormone levels in premenopausal women. Cancer Epidemiology, Biomarkers & Prevention 13 1736–1744.CrossRefGoogle ScholarPubMed
Maskarinec, G & Meng, L (2001) An investigation of soy intake and mammographic characteristics in Hawaii. Breast Cancer Research 3 134–141.CrossRefGoogle ScholarPubMed
Maskarinec, G, Williams, AE & Carlin, L (2003) Mammographic densities in a one-year isoflavone intervention. European Journal of Cancer Prevention 12 165–169.CrossRefGoogle Scholar
Morabito, N, Crisafulli, A, Vergara, C, Gaudio, A, Lasco, A, Frisina, N et al. (2002) Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. Journal of Bone and Mineral Research 17 1904–1912.CrossRefGoogle Scholar
Nestel, PJ, Pomeroy, S, Kay, S, Komesaroff, P, Behrsing, J, Cameron, JD & West, L (1999) Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women. Journal of Clinical Endocrinology and Metabolism 84 895–898.Google Scholar
Nestel, PJ, Yamashita, T, Sasahara, T, Pomeroy, S, Dart, A, Komesaroff, P, Owen, A & Abbey, M (1997) Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arteriosclerosis, Thrombosis, and Vascular Biology 17 3392–3398.CrossRefGoogle Scholar
Nikander, E, Kilkkinen, A, Metsa-Heikkila, M, Adlercreutz, H, Pietinen, P, Tiitinen, A & Ylikorkala, O (2003) A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients. Obstetrics and Gynecology 101 1213–1220.Google ScholarPubMed
Nishi, M, Yoshida, K, Hirata, K & Miyake, H (1997) Eating habits and colorectal cancer. Oncology Reports 4 995–998.Google ScholarPubMed
Penotti, M, Fabio, E, Modena, AB, Rinaldi, M, Omodei, U & Vigano, P (2003) Effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries. Fertility and Sterility 79 1112–1117.CrossRefGoogle ScholarPubMed
Petri Nahas, E, Nahas Neto, J, De Luca, L, Traiman, P, Pontes, A & Dalben, I (2004) Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy. Maturitas 48 372–380.CrossRefGoogle ScholarPubMed
Potter, SM, Baum, JA, Teng, HY, Stillman, RJ, Shay, NF & Erdman, JW (1998) Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. American Journal of Clinical Nutrition 68 1375S–1379S.CrossRefGoogle ScholarPubMed
Puska, P, Korpelainen, V, Hoie, LH, Skovlund, E, Lahti, T & Smerud, KT (2002) Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial. European Journal of Clinical Nutrition 56 352–357.CrossRefGoogle ScholarPubMed
Rowland, I, Wiseman, H, Sanders, T, Adlercreutz, H & Bowey, E (1999) Metabolism of oestrogens and phytoestrogens: role of the gut microflora. Biochemical Society Transactions 27 304–308.CrossRefGoogle ScholarPubMed
Scambia, G, Mango, D, Signorile, PG, Angeli, RA, Palena, C, Gallo, D, Bombardelli, E, Morazzoni, P, Riva, A & Mancuso, S (2000) Clinical effects of a standardized soy extract in postmenopausal women: A pilot study. Menopause 7 105–111.CrossRefGoogle ScholarPubMed
Seow, A, Quah, SR, Nyam, D, Straughan, PT, Chua, T & Aw, TC (2002) Food groups and the risk of colorectal carcinoma in an Asian population. Cancer 95 2390–2396.CrossRefGoogle Scholar
Setchell, KD (1998) Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. American Journal of Clinical Nutrition 68 1333S–1346S.Google ScholarPubMed
Setchell, KD, Borriello, SP, Hulme, P, Kirk, DN & Axelson, M (1984) Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. American Journal of Clinical Nutrition 40 569–578.CrossRefGoogle ScholarPubMed
Setchell, KD, Brown, NM, Desai, P, Zimmer-Nechemias, L, Wolfe, BE, Brashear, WT, Kirschner, AS, Cassidy, A & Heubi, JE (2001) Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. Journal of Nutrition 131 1362S–1375S.CrossRefGoogle ScholarPubMed
Setchell, KD, Brown, NM, Desai, PB, Zimmer-Nechimias, L, Wolfe, B, Jakate, AS, Creutzinger, V & Heubi, JE (2003 a) Bioavailability, disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes. Journal of Nutrition 133 1027–1035.CrossRefGoogle ScholarPubMed
Setchell, KD, Brown, NM, Lydeking-Olsen, E (2002 a) The clinical importance of the metabolite equol – a clue to the effectiveness of soy and its isoflavones. Journal of Nutrition 132 3577–3584.CrossRefGoogle Scholar
Setchell, KD, Brown, NM, Zimmer-Nechemias, L, Brashear, WT, Wolfe, BE, Kirschner, AS, Heubi, JE (2002 b) Evidence for lack of absorption of soy isoflavine glycosides in humans, supporting the crucial role of intestinal metabolism for bioavailability. American Journal of Clinical Nutrition 76 447–453.CrossRefGoogle ScholarPubMed
Setchell, KD, Faughnan, MS, Avades, T, Zimmer-Nechemias, L, Brown, NM, Wolfe, BE, Brashear, WT, Desai, P, Oldfield, MF, Botting, NP & Cassidy, A (2003 b) Comparing the pharmacokinetics of daidzein and genistein with the use of 13C-labeled tracers in premenopausal women. American Journal of Clinical Nutrition 77 411–419.CrossRefGoogle ScholarPubMed
Setchell, KD, Zimmer-Nechemias, L, Cai, J & Heubi, JE (1997) Exposure of infants to phyto-oestrogens from soy-based infant formula. Lancet 350 23–27.CrossRefGoogle ScholarPubMed
Shelnutt, SR, Cimino, CO, Wiggins, PA, Ronis, MJ & Badger, TM (2002) Pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein in men and women after consumption of a soy beverage. American Journal of Clinical Nutrition 76 588–594.CrossRefGoogle ScholarPubMed
Shu, XO, Jin, F, Dai, Q, Wen, W, Potter, JD, Kushi, LH, Ruan, Z, Gao, YT & Zheng, W (2001) Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiology, Biomarkers & Prevention 10 483–488.Google ScholarPubMed
Simons, LA, von Konigsmark, M, Simons, J & Celermajer, DS (2000) Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women. American Journal of Cardiology 85 1297–1301.CrossRefGoogle ScholarPubMed
Squadrito, F, Altavilla, D, Crisafulli, A, Saitta, A, Cucinotta, D, Morabito, N, D'Anna, R, Corrado, F, Ruggeri, P, Frisina, N & Squadrito, G (2003) Effect of genistein on endothelial function in postmenopausal women: a randomized, double-blind, controlled study. American Journal of Medicine 114 470–476.CrossRefGoogle ScholarPubMed
Squadrito, F, Altavilla, D, Morabito, N, Crisafulli, A, D'Anna, R, Corrado, F, Ruggeri, P, Campo, GM, Calapai, G, Caputi, AP & Squadrito, G (2002) The effect of the phytoestrogen genistein on plasma nitric oxide concentrations, endothelin-1 levels and endothelium dependent vasodilation in postmenopausal women. Atherosclerosis 163 339–347.CrossRefGoogle ScholarPubMed
St Germain, A, Peterson, CT, Robinson, JG & Alekel, L (2001) Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment. Menopause 8 17–26.CrossRefGoogle Scholar
Steinberg, FM, Guthrie, NL, Villablanca, AC, Kumar, K & Murray, MJ (2003) Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women. American Journal of Clinical Nutrition 78 123–130.CrossRefGoogle ScholarPubMed
Tajima, K & Tominaga, S (1985) Dietary habits and gastro-intestinal cancers: a comparative case-control study of stomach and large intestinal cancers in Nagoya, Japan. Japanese Journal of Cancer Research 76 705–716.Google ScholarPubMed
Teede, HJ, Dalais, FS, Kotsopoulos, D, Liang, YL, Davis, S & McGrath, BP (2001) Dietary soy has both beneficial and potentially adverse cardiovascular effects: a placebo-controlled study in men and postmenopausal women. Journal of Clinical Endocrinology and Metabolism 86 3053–3060.Google ScholarPubMed
Teede, HJ, Dalais, FS, Kotsopoulos, D, McGrath, BP, Malan, E, Gan, TE & Peverill, RE (2005) Dietary soy containing phytoestrogens does not activate the hemostatic system in postmenopausal women. Journal of Clinical Endocrinology and Metabolism 90 1936–1941.CrossRefGoogle Scholar
Teede, HJ, McGrath, BP, DeSilva, L, Cehun, M, Fassoulakis, A & Nestel, PJ (2003) Isoflavones reduce arterial stiffness: a placebo-controlled study in men and postmenopausal women. Arteriosclerosis, Thrombosis, and Vascular Biology 23 1066–1071.CrossRefGoogle ScholarPubMed
Tew, BY, Xu, X, Wang, HJ, Murphy, PA & Hendrich, S (1996) A diet high in wheat fiber decreases the bioavailability of soybean isoflavones in a single meal fed to women. Journal of Nutrition 126 871–877.CrossRefGoogle Scholar
Turner, R, Baron, T, Wolffram, S, Minihane, AM, Cassidy, A, Rimbach, G & Weinberg, PD (2004) Effect of circulating forms of soy isoflavones on the oxidation of low density lipoprotein. Free Radical Research 38 209–216.CrossRefGoogle ScholarPubMed
Upmalis, DH, Lobo, R, Bradley, L, Warren, M, Cone, FL & Lamia, CA (2000) Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: A multicenter, double-blind, randomized, placebo-controlled study. Menopause 7 236–242.CrossRefGoogle ScholarPubMed
van de Weijer, PH & Barentsen, R (2002) Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas 42 187–193.CrossRefGoogle ScholarPubMed
van Patten, CL, Olivotto, IA, Chambers, GK, Gelmon, KA, Hislop, TG, Templeton, E, Wattie, A & Prior, JC (2002) Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. Journal of Clinical Oncology 20 1449–1455.CrossRefGoogle ScholarPubMed
Vigna, GB, Pansini, F, Bonaccorsi, G, Albertazzi, P, Donega, P, Zanotti, L, De Aloysio, D, Mollica, G & Fellin, R (2000) Plasma lipoproteins in soy-treated postmenopausal women: a double-blind, placebo-controlled trial. Nutrition, Metabolism and Cardiovascular Diseases 10 315–322.Google ScholarPubMed
Wangen, KE, Duncan, AM, Xu, X & Kurzer, MS (2001) Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. American Journal of Clinical Nutrition 73 225–231.CrossRefGoogle ScholarPubMed
Washburn, S, Burke, GL, Morgan, T & Anthony, M (1999) Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause 6 7–13.Google ScholarPubMed
Watanabe, S, Yamaguchi, M, Sobue, T, Takahashi, T, Miura, T, Arai, Y, Mazur, W, Wahala, K & Adlercreutz, H (1998) Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after ingestion of 60 g baked soybean powder (kinako). Journal of Nutrition 128 1710–1715.CrossRefGoogle ScholarPubMed
Watanabe, Y, Tada, M, Kawamoto, K, Uozumi, G, Kajiwara, Y, Hayashi, K et al. (1984) A case-control study of cancer of the rectum and colon (in Japanese). Nippon Shokakibyo Gakkai Zasshi 81 185–193.Google Scholar
Weggemans, RM & Trautwein, EA (2003) Relation between soy-associated isoflavones and LDL and HDL cholesterol concentrations in humans: a meta-analysis. European Journal of Clinical Nutrition 57 940–946.CrossRefGoogle ScholarPubMed
Wilkinson, AP, Gee, JM, Dupont, MS, Needs, PW, Mellon, FA, Williamson, G & Johnson, IT (2003) Hydrolysis by lactase phlorizin hydrolase is the first step in the uptake of daidzein glucosides by rat small intestine in vitro. Xenobiotica 33 255–264.CrossRefGoogle ScholarPubMed
Witte, JS, Longnecker, MP, Bird, CL, Lee, ER, Frankl, HD & Haile, RW (1996) Relation of vegetable, fruit, and grain consumption to colorectal adenomatous polyps. American Journal of Epidemiology 144 1015–1025.CrossRefGoogle ScholarPubMed
Wu, AH, Wan, P, Hankin, J, Tseng, CC, Yu, MC & Pike, MC (2002) Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis 23 1491–1496.CrossRefGoogle ScholarPubMed
Wu, AH, Ziegler, RG, Horn-Ross, PL, Nomura, AM, West, DW, Kolonel, LN, Rosenthal, JF, Hoover, RN & Pike, MC (1996) Tofu and risk of breast cancer in Asian-Americans. Cancer Epidemiology, Biomarkers & Prevention 5 901–906.Google ScholarPubMed
Xu, X, Wang, HJ, Murphy, PA & Hendrich, S (2000) Neither background diet nor type of soy food affects short-term isoflavone bioavailability in women. Journal of Nutrition 130 798–801.CrossRefGoogle ScholarPubMed
Xu, Z, Wu, Q & Godber, JS (2002) Stabilities of daidzin, glycitin, genistin, and generation of derivatives during heating. Journal of Agricultural and Food Chemistry 50 7402–7406.CrossRefGoogle ScholarPubMed
Yamamoto, S, Sobue, T, Kobayashi, M, Sasaki, S & Tsugane, S (2003) Soy, isoflavones, and breast cancer risk in Japan. Journal of the National Cancer Institute 95 906–913.CrossRefGoogle ScholarPubMed
Yeung, J & Yu, TF (2003) Effects of isoflavones (soy phyto-estrogens) on serum lipids: a meta-analysis of randomized controlled trials. Nutrition Journal 2 15CrossRefGoogle ScholarPubMed
Yuan, JM, Wang, QS, Ross, RK, Henderson, BE & Yu, MC (1995) Diet and breast cancer in Shanghai and Tianjin, China. British Journal of Cancer 71 1353–1358.CrossRefGoogle ScholarPubMed
Zhang, Y, Hendrich, S & Murphy, PA (2003) Glucuronides are the main isoflavone metabolites in women. Journal of Nutrition 133 399–404.CrossRefGoogle ScholarPubMed
Zheng, W, Dai, Q, Custer, LJ, Shu, XO, Wen, WQ, Jin, F & Franke, AA (1999) Urinary excretion of isoflavonoids and the risk of breast cancer. Cancer Epidemiology, Biomarkers & Prevention 8 35–40.Google ScholarPubMed
Zubik, L & Meydani, M (2003) Bioavailability of soybean isoflavones from aglycone and glucoside forms in American women. American Journal of Clinical Nutrition 77 1459–1465.CrossRefGoogle ScholarPubMed