HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Uesugi, T. Articles by Yamori, Y. Search for Related Content PubMed PubMed Citation Articles by Uesugi, T. Articles by Yamori, Y.

Beneficial Effects of Soybean Isoflavone Supplementation on Bone Metabolism and Serum Lipids in Postmenopausal Japanese Women: A Four-Week Study

Fujicco Co., Ltd., Kobe (T.U., Y.F.), WHO Collaborating Center for Research on Primary Prevention of Cardiovascular Diseases, JAPAN
Department of Environmental Preservation and Development, Graduate School of Human and Environment Studies, Kyoto University, Kyoto (Y.Y.), JAPAN

Address reprint requests to: Yukio Yamori, MD, PhD, Director, WHO Collaborating Center for Research on Primary Prevention of Cardiovascular Diseases, Kokusaikenju Bldg, 86-2, Shimobanba-cho, Jodoji, Sakyo-ku, Kyoto 606-8413 JAPAN. Email: Yukio.Yamori{at}ma3.seikyou.ne.jp

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Objective:The aim of this study was to determine the effects of soy isoflavones with weak estrogen-like activities both on bone metabolism and on serum lipids in perimenopausal women.

Methods:Twenty-three healthy perimenopausal women were assigned randomly to either isoflavone or placebo groups. The isoflavone group (n = 12) received daily capsules of soy isoflavone extract (61.8 mg of isoflavones) and the placebo group (n = 11) received daily placebo capsules for four weeks. Urinary excretion of isoflavone was measured at weeks 0, 2 and 4. Urinary excretion of pyridinoline and deoxypyridinoline, bone stiffness and levels of serum cholesterol, triglyceride and cholesterol fractions were measured at weeks 0 and 4.

Result:As compared to the placebo group, urinary isoflavone, primarily daidzein, excretion was increased at weeks 2 and 4 in the isoflavone group. Excretion of bone resorption markers was reduced significantly in the isoflavone group. Both total serum cholesterol and LDL cholesterol were decreased significantly in the isoflavone group. Other serum biochemical parameters were not changed in either group.

Conclusions:Soy isoflavone supplementation for four weeks showed potentially beneficial effects on bone metabolism and on serum lipids in perimenopausal women. These effects could have the potential to reduce the risks of postmenopausal osteoporosis and of cardiovascular diseases in such women.

Key words: isoflavone, bone, pyridinoline, deoxypyridinoline, cholesterol, perimenopausal women

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Postmenopausal osteoporosis is associated with estrogen deficiency [1], and this can be prevented by estrogen replacement therapy (ERT) [2]. Estrogens are known to have effects not only on bone metabolism, but also on cholesterol metabolism and blood pressure [3]. Indeed, ERT is considered the most effective method of reducing bone loss and of preventing other climacteric symptoms in postmenopausal women. However such therapy may have serious side-effects [4]. For this reason, it would be desirable to identify selective estrogen receptor modulators which, while providing benefit to bone metabolism, do not increase the risk of breast cancer.

Isoflavones present one such class of estrogenic molecule. Soybean has a high isoflavone content, and it is widely consumed as a foodstuff in many Asian countries. The soybean-derived isoflavones, daidzein and genistein, and their glycosides, daidzin and genistin, have been reported to possess both estrogenic [5] and anticarcinogenic activities [6, 7].

We have shown previously that treatment with daidzin and genistin reduces bone loss and inhibits the reduction of bone strength in ovariectomized rats [8]. Epidemiological studies by our group in both native Japanese and Japanese Hawaiians have demonstrated that urinary isoflavone excretion is associated negatively with bone resorption and positively with bone density [unpublished]. Finally, an intervention study in Brazilians of Japanese ancestry, who consumed only low levels of soybean products, showed that increased ingestion of isoflavone-rich foods reduced bone loss significantly, based on the analysis of bone resorption markers in the urine [unpublished].

Native Japanese in Japan have been shown to have a much higher mean dietary intake of isoflavones than that observed in Europeans or Americans [9]. In this study, we aimed to examine the possibility that supplemental isoflavone intake would both decrease bone turnover and alter blood lipids in postmenopausal Japanese women who already have high daily dietary intakes of soybean products.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Isoflavone Extraction
Crude isoflavone extract was prepared by extracting soybean hypocotyls (100 kg) in boiling water (1000 L) for 30 minutes. The extract was poured over a synthetic resin (SP-850, Mitsubishi Chemical Industry Ltd., 70 L) for batch absorption, and the resin was then washed three times with 140 L water. After addition of 70 L 60% ethanol, the resin was stirred for 30 minutes to elute isoflavones. The elution process was repeated three times, and the combined eluate was concentrated and dried to obtain the partly-purified isoflavone extract. The extract was spray-dried with dextrin (Fujiflavone P10; Fujicco Co. Ltd., Japan) and made up into capsules, each containing 30.9 mg of isoflavones, 8.2 mg of protein, 3.3 mg of ash and 6.6 mg of water. No lipids were detectable. The isoflavone content of the extract is listed in Table 1.

Twenty-five women were recruited from among the employees of the food processing factory; of these, twenty-three subjects entered and completed the trial. Subjects were healthy perimenopausal Japanese women in the age range 40 to 62 years. For each subject, body height and weight were recorded at the beginning of the study. Twelve subjects were assigned randomly to receive soybean isoflavone extract, two capsules daily (61.8 mg of isoflavones, Table 1), and the remaining 11 subjects were assigned to receive placebo capsules containing of only dextrin for four weeks.

Isoflavone Intake
All subjects were required to keep quantitative records of all meals during the test period, in terms both of food constituents and of quantities. Based on these records, daily isoflavone intakes were calculated for each subject. Published data by Toda et al. [10] were used to determine the isoflavone content of each food item.

Bone Stiffness
Right calcaneal stiffness was measured at the beginning of the study and four weeks later, using an ultrasound bone densitometer (Achilles A-1000, Lunar Corp., Madison, WI).

Urine Analysis
Twenty-four-hour urine specimens were collected to determine isoflavone excretion at weeks 0, 2 and 4, and to determine pyridinoline and deoxypyridinolone excretion at weeks 0 and 4. After measurement of the volume, a portion of each sample (10 mL x 2 tubes) was stored at -30°C until analysis. Urinary creatinine (CRE) was determined by the Jaffe method using a commercial creatinine test kit (Wako Pure Chemical Industry, Osaka, Japan). Samples for which the CRE coefficient (mg/day/kg body weight) fell within a range of 10.8 to 25.2 were considered to represent complete urine collection and were analyzed further.

To produce free isoflavones from conjugates, urine samples were treated with sulfatase (EC 3.1.6.1 Type H-1, Sigma, St Louis, MO) and -glucuronidase (EC 3.2.1.31, Wako Pure Chemical Industries, Ltd., Japan). The reactants and urine samples were purified by Sep-pak cartridge before HPLC analysis. Quantitative HPLC analysis of urinary isoflavones was carried out in a Zorbax ODS column (4.6 mm x 25 cm; Waters) using a Waters 600 multisolvent delivery system with a WISP 710B autosampler and a Waters 490 programmable multiwavelength detector. Step gradient elution was achieved at a flow-rate of 1 mL/min with acetonitrile (A.N.) solution containing constant 0.1% acetic acid: 10% to 18% (v/v) A.N. for the first 20 minutes, 18% to 20% A.N. for another 20 minutes, and 20 to 35% A.N. for 37.5 minutes, then 35% A.N. at constant for the last seven minutes. The absorptions of urinary De and Ge were measured at 254 nm. Commercially available daidzein and genistein (Fujicco Co., Ltd.) were used for standard chemicals.

Urinary pyridinoline was determined as described by Takahashi et al. [11]. Deoxypyridinoline was determined using a commercial ELISA kit (Pyrilinks-D, Metra Biosystems, Mountain View, CA).

Blood Analyses
Venous blood (5 mL) was collected by using vacuum syringes (XX-VP010hg, Terumo Co. Ltd.) at weeks 0 and 4 and after four weeks. Immediately after collection, blood samples were centrifuged for 30 minutes at 3,000 rpm and 4°C (Model KN-30F, Kubota Co. Ltd.). Sera were stored at -30°C until analysis.

Blood tests were carried out by Aijinkai Healthcare Corp. AST, ALT and -GTP were determined spectrophotometrically [12]. Hemoglobin A1 and A1c were determined by HPLC analysis [13]. The bone formation marker osteocalcin was measured by EIA [14]. Serum triglycerides were analyzed using the GPO DAOS glycerol method [15]. Total cholesterol was determined using the cholesterol oxidase DAOS method [16]. Cholesterol fractionation was carried out by agarose gel electrophoresis [17].

Statistical Methods
StatView-j Version 4.11 (Abacus Concepts, Inc., Berkeley, CA) was utilized for statistical analysis. Differences between the means for the two groups were evaluated by using Student’s t test. Changes within each group were evaluated by using Student’s paired t test, and differences between the changes observed in each groups were evaluated by using repeated-ANOVA; p-values of less than 0.05 were considered to indicate statistically significant differences.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
There were no significant differences in age, body mass index (BMI) and time after menopause, between the test (isoflavone supplemented) and placebo groups (Table 2).

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

Daidzein and genistein, like estrogen, are thought to suppress bone resorption by attenuating the activity of osteoclasts [18, 19]. Glycitein has a weak estrogenic activity comparable to that of daidzein and genistein [20]. Genistin and daidzin have been shown to prevent bone loss in ovariectomized rats [8]. Four weeks of isoflavone supplementation appear to be effective in suppressing bone resorption in perimenopausal women (a previous report showed that estrogenic effects appeared in a short term treatment [21]). Bone metabolic parameters were changed by estrogen administration after two weeks [21]. However, bone mineral density and content change only very slowly, and a long term study would be necessary for the demonstration of the effect on bone stiffness.

Our previous epidemiological research in Japanese women has indicated a negative association between bone density and bone resorption markers such as pyridinoline [unpublished], and Tsuchida et al. reported that soybean intake was associated positively and significantly with bone mineral density in Japanese middle-aged women [29]. Higher levels of urinary pyridinoline and deoxypyridinoline excretion are associated with faster bone loss at the hip [22], and urinary deoxypyridinoline levels are reported to predict the subsequent risk of hip fracture in elderly women [23]. Inhibition of bone resorption, when not associated with reduction in bone formation, has the net effect of reducing the rate of bone loss [24]. Dalais et al. reported that diets including 45 g of soy grits containing 52.64 mg of isoflavones were associated with increased bone mineral content within 12 weeks [28]. Potter et al. reported that a diet including a high isoflavone content soy protein containing 90 mg/day of isoflavones was associated with increased bone mineral density and content within six months [25].

Based on these data, we conclude that isoflavone supplementation appears to be effective in inhibiting reduction in bone density and/or in promoting bone strength. Isoflavone supplementation in Japanese subjects, who already consume relatively high levels of soybean products, thus appears to provide further benefit to bone metabolism.

In addition to beneficial effects on bone metabolism, isoflavones lowered total serum cholesterol levels as well as LDL cholesterol. High LDL cholesterol levels are known to be associated with atherosclerosis [26]. Estrogen increases LDL catabolism by increasing the number of LDL receptors, as shown in hepatocytes from estrogen-treated rats [27]. Isoflavones may reduce LDL level by increasing the number of LDL receptors in a similar manner. Our data thus confirmed that isoflavones had beneficial effects on bone and lipid metabolisms, suggesting they may be useful for preventing both osteoporosis and coronary heart diseases. However, Potter et al. reported that isoflavones provided effective benefit to mineral density and content, but provided little benefit to blood lipids [25]. The estrogen threshold hypothesis is now widely accepted, and the positive effective dose of estrogen for the reduction of bone resorption is as low as 30 pg/mL, while for benefit to serum cholesterol much higher doses are necessary [30]. Our observations support this hypothesis. Since the isoflavone extract used in this study included large amounts of daidzin and glycitin, a small amount of genistin, but little soy protein, the observed benefits appear to be attributable to isoflavones and mainly to daidzin and glycitin.

Isoflavone supplementation at this level over four weeks appears to be safe, as judged by clinical laboratory blood tests, physical examinations and on the basis of subjective symptoms. No side effects were detected.

	CONCLUSIONS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Daily supplementation of soybean isoflavones (61.8 mg) for four weeks was associated with a significant reduction in the excretion of bone resorption markers (pyridinoline and deoxypyridinoline), concomitantly with marked increases in urinary daidzein excretion and with lowered serum total and LDL cholesterol levels in postmenopausal Japanese women.

Isoflavone supplementation at this daily dose for four weeks did not affect liver function, and the benefits of soy isoflavone supplementation for reducing risks of osteoporosis and coronary heart disease appear not to be associated with any deleterious metabolic effects.

Received May 31, 2000. Accepted July 31, 2001.

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 

1. Gibaldi M: Prevention and treatment of osteoporosis: Does the future belong to hormone replacement therapy? J Clin Pharmacol 37: 1087–1099, 1997.[Abstract]
2. Lindsay R, Hart DM, Clark DM: The minimum effective dose of estrogen for prevention of postmenopausal bone loss. Obstet Gynecol 63: 759–763, 1984.[Abstract/Free Full Text]
3. Walsh BW, Schiff I, Rosner B, Greenberg L, Ravnikar V, Sacks FM: Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. N Engl J Med 325: 1196–1204, 1991.[Abstract]
4. Colditz GA, Stampfer MJ, Willett WC, Hennekens C, Rosner B, Speizaer FD: Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women. JAMA 264: 2648–2653, 1990.[Abstract]
5. Bickoff EM, Livingston AL, Hendrickson AP, Booth AN: Relative potencies of several estrogen-like compounds found in forages. J Agric Food Chem 10: 410–412, 1962.
6. Peterson G, Barnes S: Genistein inhibition of the growth of human breast cancer cells: Independence from estrogen receptors and the multi-drug resistance gene. Biochem Biophys Res Commun 179: 661–667, 1991.[Medline]
7. Mousavi Y, Adlercreutz H: Genistein is an effective stimulator of sex hormone-binding globulin production in hepatocarcinoma human liver cancer cells and suppresses proliferation of these cells in culture. Steroids 58: 301–304, 1993.[Medline]
8. Ishida H, Uesugi T, Hirai K, Toda T, Nukaya H, Yokotsuka K, Tsuji K: Preventive effects of the plant isoflavones, daidzin and genistin, on bone loss in ovariectomized rats fed a calcium-deficient diet. Biol Pharm Bull 21: 62–66, 1998.[Medline]
9. Adlercreutz H, Honjo H, Higashi A, Fotsis T, Hamalainen E, Hasegawa T, Okada H: Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet. Am J Clin Nutr 54: 1093–1100, 1991.[Abstract/Free Full Text]
10. Toda T, Tamura J, Okuhira T: Isoflavone contents of commercial soy foods. FFI J Jpn 172: 83–89, 1997.
11. Takahashi M, Ohishi T, Aoshima H, Kushida K, Inoue T, Horiuchi K: Pre-fractionation with cation exchanger for determination of intermolecular crosslinks, pyridinoline, and pentosidine, in hydrolysate. J Liquid Chromatogr 16: 1355–1370, 1993.
12. Shaw LM, Stromme JH, London JL, Theodorsen L: International Federation of Clinical Chemistry, (IFCC), Scientific committee, Analytical section. IFCC methods for the measurement of catalytic concentration of enzymes. Part 4. IFCC method for gamma-glutamyltransferase [(gamma-glutamyl)-peptide: amino acid gamma-glutamyltransferase, EC 2.3.2.2]. J Clin Chem Biochem 21: 633–646, 1983.
13. Goldstein DE, Peth SB, England JD, Hess RL, Da Costa J: Effects of acute changes in blood glucose on Hb A1c. Diabetes 29: 623–627, 1980.[Medline]
14. Hosoda K, Eguchi H, Nakamoto T, Kubota T, Honda H, Jindai S, Hasegawa R, Kiyoki M, Yamaji T, Shiraki M: Sandwich immunoassay for intact human osteocalcin. Clin Chem 38: 2233–2238, 1992.[Abstract/Free Full Text]
15. Spayd RW, Bruschi B, Burdick BA, Dappen GM, Eikenberry JN, Esders TW, Figueras J, Goodhue CT, LaRossa DD, Nelson RW, Rand RN, Wu TW: Multilayer film elements for clinical analysis: applications to representative chemical determinations. Clin Chem 24: 1343–1350, 1978.[Abstract/Free Full Text]
16. Allain CC, Poon LS, Chan CSG, Richmond W, Fu PC: Enzymatic determination of total serum cholesterol. Clin Chem 20: 470–475, 1974.[Abstract]
17. Phillips GB, Wille LE: The phospholipid composition of human serum lipoprotein fractions separated by electrophoresis on agarose gel. Demonstration of a fraction with high lysolecithin content. Clin Chim Acta 49: 153–160, 1973.[Medline]
18. Gao YH, Yamaguchi M: Anabolic effect of daidzein on cortical bone in tissue culture: Comparison with genistein effect. Mol Cell Biochem 194; 93–98, 1999.[Medline]
19. Yamaguchi M, Gau YH: Inhibitory effect of genistein on bone resorption in tissue culture. Biochem Pharm 55: 71–76, 1998.[Medline]
20. Song TT, Hendrich S, Murphy PA: Estrogenic activity of glycitein, a soy isoflavone. J Agric Food Chem 47: 1607–1610, 1999.[Medline]
21. Stock JL, Coderre JA, Mallette LE: Effects of a short course of estrogen on mineral metabolism in post menopausal women. Endocrinol Metab 61: 595–600, 1985.
22. Bauer DC, Sklarin PM, Stone KL, Black DM, Nevitt MC, Ensrud KE, Arnaud CD, Genant HK, Garnero P, Delmas PD, Lawaetz H, Cummings SR: Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures. J Bone Miner Res 14: 1404–1410, 1999.[Medline]
23. Garnero P, Hausherr E, Chapuy MC, Marcelli C, Grandjean H, Muller C, Cormier C, Breart G, Meunier PJ, Delmas PD: Markers of bone resorption predict hip fracture in elderly women: the EPIDOS prospective study. J Bone Miner Res 11: 1531–1538, 1996.[Medline]
24. Garnero P, Shih WJ, Gineyts E, Karpf DB, Delmas PD: Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. J Clin Endocrinol Metab 79: 1693–1700, 1994.[Abstract]
25. Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman Jr JW: Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68: 1375–1379, 1998.
26. Steinberg D: Antioxidants and atherosclerosis: a current assessment. Circulation 84: 1421–1425, 1991.
27. Windler E, Kovanen PT, Chao YS, Brown MS, Havel RJ, Goldstein JL: The estradiol-stimulated lipoprotein receptor of rat liver. J Biol Chem 255: 10464–10471, 1980.[Abstract/Free Full Text]
28. Dalais FS, Rice GE, Wahlqvist ML, Grehan M, Murkies AL, Medley G, Ayton R, Strauss BJG: Effects of dietary phytoestrogens in postmenopausal women. Climacteric 1: 124–129, 1998.[Medline]
29. 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: 14–19, 1999.[Medline]
30. Barbieri RL: Hormone treatment of endometriosis: The estrogen threshold hypothesis. Am J Obstet Gynecol 166: 740–745, 1992.[Medline]

This article has been cited by other articles:

				A. Orgaard and L. Jensen The Effects of Soy Isoflavones on Obesity Experimental Biology and Medicine, September 1, 2008; 233(9): 1066 - 1080. [Abstract] [Full Text] [PDF]

				C. Clerici, K. D. R. Setchell, P. M. Battezzati, M. Pirro, V. Giuliano, S. Asciutti, D. Castellani, E. Nardi, G. Sabatino, S. Orlandi, et al. Pasta Naturally Enriched with Isoflavone Aglycons from Soy Germ Reduces Serum Lipids and Improves Markers of Cardiovascular Risk J. Nutr., October 1, 2007; 137(10): 2270 - 2278. [Abstract] [Full Text] [PDF]

				A. Dewell, P. L. W. Hollenbeck, and C. B. Hollenbeck A Critical Evaluation of the Role of Soy Protein and Isoflavone Supplementation in the Control of Plasma Cholesterol Concentrations J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 772 - 780. [Abstract] [Full Text] [PDF]

				B. L McVeigh, B. L Dillingham, J. W Lampe, and A. M Duncan Effect of soy protein varying in isoflavone content on serum lipids in healthy young men Am. J. Clinical Nutrition, February 1, 2006; 83(2): 244 - 251. [Abstract] [Full Text] [PDF]

				X. Zhang, X.-O. Shu, H. Li, G. Yang, Q. Li, Y.-T. Gao, and W. Zheng Prospective Cohort Study of Soy Food Consumption and Risk of Bone Fracture Among Postmenopausal Women Arch Intern Med, September 12, 2005; 165(16): 1890 - 1895. [Abstract] [Full Text] [PDF]

				W.-H. Wu, L.-Y. Liu, C.-J. Chung, H.-J. Jou, and T.-A. Wang Estrogenic Effect of Yam Ingestion in Healthy Postmenopausal Women J. Am. Coll. Nutr., August 1, 2005; 24(4): 235 - 243. [Abstract] [Full Text] [PDF]

				S. Dodin, A. Lemay, H. Jacques, F. Legare, J.-C. Forest, and B. Masse The Effects of Flaxseed Dietary Supplement on Lipid Profile, Bone Mineral Density, and Symptoms in Menopausal Women: A Randomized, Double-Blind, Wheat Germ Placebo-Controlled Clinical Trial J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1390 - 1397. [Abstract] [Full Text] [PDF]

				Y. T. van der Schouw, L. Sampson, W. C. Willett, and E. B. Rimm The Usual Intake of Lignans but Not That of Isoflavones May Be Related to Cardiovascular Risk Factors in U.S. Men J. Nutr., February 1, 2005; 135(2): 260 - 266. [Abstract] [Full Text] [PDF]

				G. Williamson and C. Manach Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies Am. J. Clinical Nutrition, January 1, 2005; 81(1): 243S - 255S. [Abstract] [Full Text] [PDF]

				M. S Rosell, P. N Appleby, E. A Spencer, and T. J Key Soy intake and blood cholesterol concentrations: a cross-sectional study of 1033 pre- and postmenopausal women in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition Am. J. Clinical Nutrition, November 1, 2004; 80(5): 1391 - 1396. [Abstract] [Full Text] [PDF]

				E. Nikander, A. Tiitinen, K. Laitinen, M. Tikkanen, and O. Ylikorkala Effects of Isolated Isoflavonoids on Lipids, Lipoproteins, Insulin Sensitivity, and Ghrelin in Postmenopausal Women J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3567 - 3572. [Abstract] [Full Text] [PDF]

				C. Atkinson, W. Oosthuizen, S. Scollen, A. Loktionov, N. E. Day, and S. A. Bingham 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 J. Nutr., July 1, 2004; 134(7): 1759 - 1764. [Abstract] [Full Text]

				A. Hikosaka, M. Asamoto, N. Hokaiwado, K. Kato, K. Kuzutani, K. Kohri, and T. Shirai Inhibitory effects of soy isoflavones on rat prostate carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Carcinogenesis, March 1, 2004; 25(3): 381 - 387. [Abstract] [Full Text] [PDF]

				C. Atkinson, J. E Compston, N. E Day, M. Dowsett, and S. A Bingham The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial Am. J. Clinical Nutrition, February 1, 2004; 79(2): 326 - 333. [Abstract] [Full Text] [PDF]

				M. Sagara, T. Kanda, M. NJelekera, T. Teramoto, L. Armitage, N. Birt, C. Birt, and Y. Yamori Effects of Dietary Intake of Soy Protein and Isoflavones on Cardiovascular Disease Risk Factors in High Risk, Middle-Aged Men in Scotland J. Am. Coll. Nutr., February 1, 2004; 23(1): 85 - 91. [Abstract] [Full Text] [PDF]

				C. E. Piersen Phytoestrogens in Botanical Dietary Supplements: Implications for Cancer Integr Cancer Ther, June 1, 2003; 2(2): 120 - 138. [Abstract] [PDF]

				S. C. Blum, S. N. Heaton, B. M. Bowman, M. Hegsted, and S. C. Miller Dietary Soy Protein Maintains Some Indices of Bone Mineral Density and Bone Formation in Aged Ovariectomized Rats J. Nutr., May 1, 2003; 133(5): 1244 - 1249. [Abstract] [Full Text] [PDF]

				Y. Yamori, E. H. Moriguchi, T. Teramoto, A. Miura, Y. Fukui, K.-i. Honda, M. Fukui, Y. Nara, K. Taira, and Y. Moriguchi Soybean Isoflavones Reduce Postmenopausal Bone Resorption in Female Japanese Immigrants in Brazil: A Ten-Week Study J. Am. Coll. Nutr., December 1, 2002; 21(6): 560 - 563. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Uesugi, T. Articles by Yamori, Y. Search for Related Content PubMed PubMed Citation Articles by Uesugi, T. Articles by Yamori, Y.