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 Anderson, J. J. B. Articles by Garner, S. C. Search for Related Content PubMed PubMed Citation Articles by Anderson, J. J. B. Articles by Garner, S. C.

Soy Isoflavones: No Effects on Bone Mineral Content and Bone Mineral Density in Healthy, Menstruating Young Adult Women after One Year

Department of Nutrition, Schools of Public Health and Medicine (J.J.B.A., X.C., A.B., M.K.), University of North Carolina, Chapel Hill, North Carolina
Department of Biostatistics, School of Public Health (M.S.), University of North Carolina, Chapel Hill, North Carolina
Department of Radiology, School of Medicine (J.B.R.), University of North Carolina, Chapel Hill, North Carolina
TPMC, Inc., Research Triangle Park, North Carolina (S.C.G.)

Address reprint requests to: Dr. John Anderson, Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599-7400. E-mail: jjb_anderson{at}unc.edu

	ABSTRACT

TOP FOOTNOTES ABSTRACT INTRODUCTION METHODS RESULTS ACKNOWLEDGMENTS REFERENCES

 
Background: The effects of isoflavone-enriched soy protein on human bone mineral content (mass) and density in healthy, menstruating young adult females have not been examined in a comparative prospective investigation. Peri- and post-menopausal women have been reported to show beneficial effects of isoflavones on bone measurements. Therefore, young women may also be able to improve their accrual of peak bone mineral content (BMC) and bone mineral density (BMD) during the early adult years of bone consolidation with an isoflavone-enriched diet.

Objectives: In this controlled, double-blind intervention, we tested the hypothesis that an isoflavone-rich soy protein diet increases BMC and BMD in young adult females over a period of one year in comparison to a control group receiving soy protein that has isoflavones removed.

Design: Young healthy women of any ethnic background, 21 to 25 years of age, were divided into two groups, placebo (n = 13) and supplement (n = 15). The soy protein supplement was enriched with isoflavones (90 mg of total isoflavones/day), whereas the control protein diet was isoflavone-deficient, even though it contained the same amount of soy protein and other ingredients as the isoflavone-rich diet. Dual-energy x-ray absorptiometric (DXA) measurements of BMC and BMD were made at baseline and at 6 and 12 months. DXA estimates of body composition, including fat mass and lean body mass, were generated from whole-body BMC measurements. BMI was calculated as weight (kg) over height (m) squared. Physical activity was assessed, and three-day dietary records were taken at entry (baseline) and at 6 and 12 months.

Results: No changes in BMD after 12 months were found in either the isoflavone-treated (treatment) group or the isoflavone-deficient (control) group. Other variables also remained essentially constant over the 12-month period, including normal menstrual patterns in both the treatment and control groups.

Conclusions: The isoflavone-rich soy preparation had no effects on BMC and BMD over a 12-month period in young healthy adult females with normal menses. An isoflavone-rich supplement appears to have little or no effect on bone in young adult women with normal ovarian function, at least over this 12-month study period.

Key words: soy-based supplement, isoflavones, genistein, daidzein, bone mineral content (BMC), bone mineral density (BMD), young adult women, prospective study

	INTRODUCTION

TOP FOOTNOTES ABSTRACT INTRODUCTION METHODS RESULTS ACKNOWLEDGMENTS REFERENCES

 
Few prospective investigations on the effects of soy products on human bone mineral density using a double-blind, controlled design have been reported, and none on young adult women with normal menstrual status has appeared. In earlier short-term investigations of women using soy protein isolates, bone variables were not measured [1–3]. More recently, two prospective studies lasting almost six months found significant improvements in vertebral bone mineral density (BMD) of peri- or post-menopausal women who consumed isoflavone-rich soy preparations containing approximately 90 mg per day of total isoflavones, both glycones and aglycones, per day [4–5]. The relative improvement or maintenance in vertebral BMD in the treatment groups was modest, but the control groups lost BMD over the same time. Animal studies of young ovariectomized rodents had demonstrated similar improvements in BMD or in actual mineral mass using a variety of experimental designs [7–9]. For example, whole soy [7], isoflavone-enriched preparations [8] and pure genistein [9] all produced significant or near-significant gains in bone parameters in these estrogen-depleted rodent models. When estrogen is present, rodent models seem to be little affected by a diet enriched in soy protein [10]. No prospective study has been reported on the effects of isoflavone-rich products on bone of young healthy adult women, but an observational cross-sectional study from Hong Kong reported that post-menopausal women, but not pre-menopausal, seemed to have skeletal benefits from soy consumption [11]. Therefore, prospective trials of natural soy products or soy derivatives, such as the isoflavones, would be informative in young healthy adult women to determine whether any benefits of these products can be found on bone. The potential of isoflavones to enhance peak bone mass and, hence, in turn to prevent or delay the onset of osteoporosis needs further investigation.

This study tested the hypothesis that a soy protein supplement rich in isoflavones, containing genistein, daidzein and glycitein, will increase bone mineral content (BMC) and bone mineral density (BMD) in young adult females over a one-year period in comparison to a control group consuming isoflavone-depleted soy protein. Previous reports have suggested that young adult females may still increase peak bone mass and density during these important early adult years of bone consolidation from bone-enhancing dietary factors [12–13]. The dose selected for this study, i.e., approximately 90 mg of total isoflavones (both glycones and aglycones), was selected based on previous studies of peri- or post-menopausal women which used a nearly identical dose of isoflavone-enriched soy protein from the same producer.

	METHODS

TOP FOOTNOTES ABSTRACT INTRODUCTION METHODS RESULTS ACKNOWLEDGMENTS REFERENCES

 
Study Design
We conducted a one-year, controlled, double-blind prospective investigation of normally menstruating young women. Inclusion criteria specified healthy women of any ethnic background who were between 21 and 25 years of age at entry and who would remain in the area for the duration of the study. Exclusion criteria were pregnancy/lactation, use of oral contraceptive agents or steroid hormones and continuing longitudinal growth (height).

Recruitment, Entry and Follow-up
Subjects were recruited by local advertising (notices on bulletin boards, flyers sent to organizations, local papers) in the Chapel Hill and Research Triangle areas. Rolling enrollment occurred over approximately 18 months, and assignment of subjects to treatment or control alternated in the order of enrollment. When a drop-out occurred, a new subject was added as soon as possible to equalize the numbers in the two groups. Individuals from all racial/ethnic groups were eligible to participate, but only three non-Caucasian subjects (two Americans of Asian background and one Native American) completed the study.

Initial screening and baseline measurements were made after subjects had met the inclusion/exclusion criteria and signed the consent form. The identity of control and treatment materials was not known to subjects or investigators. A pregnancy test was performed on each subject at the General Clinical Research Center (standard kit) to determine further eligibility. Measurements included baseline bone and body composition. A brief questionnaire with key health, physical activity and dietary questions, as well as a dietary recall (one-day recall and two subsequent days of records), were also recorded at baseline.

Supplements (see below) were provided for a month at a time. When they were picked up, the subjects were queried as to their compliance during the past month. Only 28 of 38 subjects who met inclusion/exclusion criteria completed the 12-months of study. Ten subjects dropped out after participating for more than a month. They dropped out for different reasons: four began using disqualifying medications, three moved away and three left for other unspecified reasons.

Subjects maintained normal menstrual cycles (nine or more menses during the 12 months) throughout the study, but one subject in the treatment group and one subject in the control group had only eight menses during the twelve months of study. Body fat content (mass), measured by DXA, ranged between 18% and 40% (Table 1) of total body weight in all subjects.

Isoflavone-Enriched and Control Preparations
Isoflavone-enriched and control soy protein isolates were gifts from Protein Technologies International, Inc., St. Louis. Both were available in a powdered form and as a ready-to-drink chocolate liquid; subjects selected according to their preference. The daily treatment dose taken by half of the study subjects contained approximately 90 mg of isoflavones (59% as glycones or glucosides; the remainder as aglycones), including at least 50 mg of genistein in both the glycone and aglycone forms. A control preparation, lacking the isoflavones, was provided; this soy isolate is similar to the isoflavone-enriched preparation, but some components, about which we have no information, may be removed during the alcohol-extraction process.

Compliance was monitored by having subjects record the days when they missed taking the supplement. A rough estimate of compliance was also achieved by noting when the monthly supply of supplements was picked up. Only one person recorded a lapse of more than seven days (one gap of one month and a subsequent one of one week). Her total time in the study was increased by almost two months to make up for the gaps in the use of supplements. After the subject treatment code was broken, she was found to be part of the group that had been receiving control soy preparation.

Anthropometrical Measurements
Measurements of height (m) and weight (kg) were made and body mass index (BMI) was calculated from these measurements as weight divided by height squared.

Bone Measurements
At baseline and six and twelve months, BMC and BMD were measured by dual energy-x-ray absorptiometry (DXA, Hologic Model 1000-W, Waltham, MA) at several sites, including the whole body and regional sites of interest. Precision of the DXA scans using human subjects was approximately 1.5% at the lumbar vertebrae and 2.0% at other sites. In vitro precision was less than 1%. These measurements were made in the Radiology Department of the University of North Carolina Hospitals.

Dietary Intake Assessment
Three times during the study, three days of dietary data (24-hour recall plus a self-administered record of two days of recorded intake) were collected and analyzed. Amounts of nutrient variables were averaged at each time-point before computing an overall average for a subject. All participants received at least 900 mg of calcium from the soy products (treatment or placebo), in addition to their usual calcium intake from food. The nutrient composition program, Food Processor, Version 7.4 (ESHA Research, Salem, OR), was used for dietary assessment.

Physical Activity Assessment
A self-reported scale of activities was used. Each subject estimated her current and past activities from inactive (0) to very active (3), and a composite score was calculated.

Statistical Analyses
Statistical comparisons of baseline characteristics and of bone and dietary measurements of the study subjects from baseline to 12 months were performed by the SAS procedure of paired t test (Version 8.0, SAS Institute, Inc., Cary, NC). Multiple regression analysis was used to determine if change in calcium intake over the 12-month period had an effect on change in BMD over the same period. A value of p < 0.05 was considered significant.

	RESULTS

TOP FOOTNOTES ABSTRACT INTRODUCTION METHODS RESULTS ACKNOWLEDGMENTS REFERENCES

 
Baseline Characteristics
A total of 28 healthy young women who met the inclusion/exclusion criteria finished this study. Table 1 shows their baseline characteristics. Differences between the subjects in treatment and control groups were minimal, with the exception that mean values for BMI, body weight, fat mass and lean body mass (LBM) were significantly higher in the treatment group.

Only baseline and 12-month data are included in the Results because the six-month data were very similar to the 12-month data.

Body Composition Measurements
The mean fat mass of the treatment and control groups remained remarkably similar from baseline to 12 months. LBM also changed little in the two groups over the 12-month period. No significant differences of these variables were found between measurement times.

Bone Measurements
Few differences were found in BMD and BMC measurements between the two groups at baseline or after 12 months, but for two sites BMC values, femoral neck and intertrochanter, were significantly reduced in the supplement group (Table 2). BMD changes were insignificant except for the femoral neck. Differences between control and treatment groups were only significant for the femoral neck and intertrochanter, both declines in the treatment group (Table 2).

	DISCUSSION

 
At 12 months, no gains of BMC and BMD in either the isoflavone supplement or control groups of this study were found, and no differences in mean bone measurements were found between the treatment and control groups. (The decreases in BMC-IT and BMD-NK in the isoflavone-rich group at 12 months are considered to be inconsistent and not meaningful.) Even after regression adjustment for possible differences in calcium intakes, no differences in BMD persisted for the control or soy-isoflavone supplement groups in comparison to baseline values. The lack of an effect of soy isoflavones (90 mg per day) on BMD, considered a better index for the comparative evaluation of bone health than BMC in adults, does not support our original hypothesis. Our findings suggest that any gains in BMD from consumption of an isoflavone-rich diet in healthy young adult women with normal menstrual cycles are unlikely. Because these results in normally cycling young women are clearly different from the findings of post- [4] and peri-menopausal women [5], who were administered similar doses of isoflavones (total), from practically the same soy protein preparation, an explanation for a lack of an effect in our intervention may be the difference in estrogen status of the young subjects, i.e., with sufficient ovarian function, compared to the older menopausal or peri-menopausal subjects, i.e., with ovarian hormone deficiency.

The mechanism through which isoflavones are thought to benefit bone in estrogen-depleted menopausal women relates to actions of the isoflavones on estrogen receptors and other cellular pathways of bone osteoblastic cells [14]. Studies using an ovariectomized (OVX) animal model by our group [8] and others [7,9] have clearly demonstrated significant positive skeletal effects of soy protein or genistein preparations at doses comparable to the effects of physiological doses of estrogenic molecules in young estrogen-depleted rodents. A biphasic response to the isoflavone-rich soy preparation has also been reported in these OVX rat models [8]; this suggests that high doses may have suboptimal benefits or even adverse effects on the animals. Interpretation of these animal-based results suggests that, at modest doses, the soy isoflavones, or genistein alone, appear to act as an agonist at the estrogen receptor (ER), whereas at higher doses the isoflavones may be less effective in their effects on bone. In addition to the effects of isoflavones on the estrogen receptors of bone cells, genistein and other isoflavones may also exert additional actions that generally enhance osteoblastic cell functions and reduce osteoclast-mediated bone resorption [15–17]. At dietarily achievable levels, genistein has been shown to function as a weak estrogen agonist in osteoblast-like cells via ERs [14,18].

Young adult women may be beyond the window of opportunity for skeletal benefits because ovarian hormone production maintains sufficiently high circulating concentrations of estrogen. Increased intakes of isoflavones from soy consumption early in adult life probably are not able to improve bone mass, because the ERs of osteoblasts have a greater affinity for estradiol than for genistein or daidzein [19]. The isoflavones may have agonistic effects on bone, but the effects of endogenous estrogens are far greater so that the effects of the isoflavone benefits are overshadowed, as suggested by Duncan et al. [20]. This interpretation probably also extends to pre-menopausal adult Asian women who consume large amounts of soy products on a regular basis, but may not hold for post-menopausal Asian women whose bone mass may benefit from routine soy consumption [21].

Although isoflavones had no skeletal benefits in the healthy young women of this study, the women may have received other benefits from soy, but these were not measured. For example, their cardiovascular and other systems may have benefited from soy protein consumption [22].

No adverse effects from the supplementation with the isoflavone-rich preparation, such as gastrointestinal disturbances, were reported by the subjects. Body composition values of fat mass and LBM changed very little over the year, and throughout the 12 months, menstrual cycles remained normal for almost all subjects regardless of treatment. Every indication from the subjects themselves suggests that the isoflavone-rich soy preparation was safe.

Limitations of this study are several, including a small sample size and a 26% drop-out rate. We think that selection bias was not introduced by the alternating assignment of subjects to the two groups, nor by haphazard replacement of dropouts, but the study was not truly randomized. Despite the small sample size, the lack of any positive gains in BMC or BMD of the isoflavone-treated subjects makes unlikely any benefits to bone from additional amounts of isoflavones. Larger numbers of subjects in the two groups are unlikely to increase the chance of finding a skeletal benefit, since the estimates of effects were small or negative. At present, no other studies are available to confirm the negative results of this report. One year of study may be too short a time to be able to determine if isoflavones have the potential for a long-term reduction of osteoporosis and fracture risks, but in studies of peri- or postmenopausal women six months was sufficient to show differences between treatment and control groups. Longer controlled investigations, similar to the present one, are needed to establish an effect of isoflavones as bone-promoting and anti-osteoporotic agents.

In summary, the isoflavone-rich preparation had no effect on BMC or BMD of the whole body or of several specific skeletal sites (lumbar spine and proximal femur) after one year of treatment in young healthy adult females with normal menses. The only differences in skeletal measurements found between control and isoflavone-treated subjects are considered of little meaning and inconsistent with the rest of the findings. These results from healthy young women suggest that isoflavones have little influence on bone compared to endogenous estrogens. The use of pure genistein to determine if this isoflavone can improve bone mass and density in a controlled randomized clinical trial would be an excellent basis for a future study.

	ACKNOWLEDGMENTS

TOP FOOTNOTES ABSTRACT INTRODUCTION METHODS RESULTS ACKNOWLEDGMENTS REFERENCES

 
The help of the GCRC where much of this study took place is greatly appreciated (sponsored by M01 RR00046 from the National Institutes of Health, National Center for Research Resources, General Clinical Research Center). The study was supported by research grant #7344 of the United Soybean Board (USB), St. Louis, and we thank their technical staff for help in making the soy preparations more acceptable to the subjects. We also thank William Myers, MD, Department of Obstetrics and Gynecology, for his advice in evaluating menstrual cycle patterns of the subjects in this study and Boyd Switzer, PhD, for assistance in this study. The DXA measurements were performed by Debbie Riggs, RT, and other Radiologic Technicians at UNC Hospitals, who are duly acknowledged for their good efforts. Gifts of soy preparations were received from Protein Technologies International, St. Louis.

	FOOTNOTES

TOP FOOTNOTES ABSTRACT INTRODUCTION METHODS RESULTS ACKNOWLEDGMENTS REFERENCES

 
Grant support was received from the United Soybean Board, Chesterfield, MO.

Received August 1, 2001. Accepted April 19, 2002.

	REFERENCES

TOP FOOTNOTES ABSTRACT INTRODUCTION METHODS RESULTS ACKNOWLEDGMENTS REFERENCES

 

1. Baird DD, Umbach DM, Lansdell L, Hughes CL, Setchell KD, Weinberg CR, Haney AF, Wilcox AJ, Mclachlan JA: Dietary intervention study to assess estrogenicity of dietary soy among postmenopausal women.J Clinic Endocrinol Metab80 :1685 –1690,1995 .[Abstract/Free Full Text]
2. Wilcox G, Wahlqvist ML, Burger HG, Medley G: Oestrogenic effects of plant foods in postmenopausal women.BMJ301 :905 –906,1990 .
3. Murkies AL, Lombard C, Strauss BJ, Wilcox G, Burger HG, Morton MS: Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat.Maturitas.21 :189 –195,1995 .[Medline]
4. 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 Nutr68 :1375S –1379S,1998 .[Abstract]
5. Alekel DL, St Germain A, 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 Nutr72 :844 –852,2000 .[Abstract/Free Full Text]
6. Wangen KE, Duncan AM, Merz-Demlow BE, Xu X, Marcus R, Phipps WR, Kurzer MS: Effects of soy isoflavones on markers of bone turnover of premenopausal and postmenopausal women.J Clin Endocrinol Metab85 :3043 –3048,2000 .[Abstract/Free Full Text]
7. Arjmandi BH, Birnbaum R, Goyal NV, Getlinger MJ, Juma S, Alekel L, Hasler CM, Drum ML, Hollis BW, Kukreja SC: Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content.Am J Clin Nutr68 :1364S –1368S,1998 .[Abstract]
8. Anderson JJB, Ambrose WW, Garner SC: Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model.Proc Soc Exp Biol Med217 :345 –352,1998 .[Abstract]
9. Blair HC, Jordan SE, Peterson TG, Barnes S: Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats.J Cell Biochem61 :629 –637,1996 .[Medline]
10. Wilson TA, Garner SC, Anderson JJB: Dietary protein source and serum estradiol concentrations of rats during pregnancy, lactation and post-lactation.Nutr Res20 :1735 –1747,2000 .
11. Mei J, Yeung SSC, Kung AWC: High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women.J Clin Endocrinol Metab86 :5217 –5221,2001 .[Abstract/Free Full Text]
12. Haapasalo H, Kannus P, Sievanen H, Pasanen M, Uusi-Rasi K, Heinonen A, Oja P, Vuori I: Development of mass, density, and estimated mechanical characteristics of bones in Caucasian females.J Bone Miner Res11 :1751 –1760,1996 .[Medline]
13. Anderson JJB, Rondano PA: Peak bone mass development of females: can young adult women improve their peak bone mass?J Am Coll Nutr15 :570 –574,1996 .[Abstract]
14. Anderson JJB, Garner SC: Phytoestrogens and bone.Balliere’s Clin Endocrinol Metab12 :1 –15,1998 .[Medline]
15. Sugimoto E, Yamaguchi M: Anabolic effect of genistein in osteoblastic MC3T3-E1 cells.Int J Mol Med5 :515 –520,2000 .[Medline]
16. Gao YH, Yamaguchi M: Suppressive effect of genistein on rat bone osteoclasts: involvement of protein kinase inhibition and protein tyrosine phosphatase activation.Int J Mol Med5 :261 –267,2000 .[Medline]
17. Chen XW, Garner SC, Anderson JJB: Effects of 17beta-estradiol (E2) and genistein (GEN) on IL-6 synthesis in relation to expression of estrogen receptors (ER) alpha and beta during differentiation in MC3T3-E1 cells [Abstract #679.6].FASEB J13 :A911 ,1999 .
18. Hsieh CY, Santell RC, Haslam SZ, Helferich WG: Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo.Cancer Res58 :3833 –3838,1998 .[Abstract/Free Full Text]
19. Miksicek RJ: Interaction of naturally occurring nonsteroidal estrogens with expressed recombinant human estrogen receptor.J Steroid Biochem Molec Biol49 :153 –160,1994 .[Medline]
20. Duncan AM, Merz BE, Xu X, Nagel TC, Kurzer MS: Soy isoflavones exert modest hormonal effects in premenopausal women.J Clin Endocrinol Metab84 :192 –197,1999 .[Abstract/Free Full Text]
21. Anderson JJB: Plant-based diets and bone health: nutritional implications.Am J Clin Nutr70 :539S –542S,1990 .[Abstract/Free Full Text]
22. Clarkson T, Anthony M, Morgan TM: Inhibition of postmenopausal atherosclerosis progression: a comparison of the effects of conjugated equine estrogens and soy phytoestrogens.J Clin Endocrinol Metab86 :41 –47,2001 .[Abstract/Free Full Text]

This article has been cited by other articles:

				C. J Lees, J. R Kaplan, H. Chen, C. P Jerome, T. C Register, and A. A Franke Bone mass and soy isoflavones in socially housed, premenopausal macaques Am. J. Clinical Nutrition, July 1, 2007; 86(1): 245 - 250. [Abstract] [Full Text] [PDF]

				J. M. K. Cheong, B. R. Martin, G. S. Jackson, D. Elmore, G. P. McCabe, J. R. Nolan, S. Barnes, M. Peacock, and C. M. Weaver Soy Isoflavones Do Not Affect Bone Resorption in Postmenopausal Women: A Dose-Response Study Using a Novel Approach with 41Ca J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 577 - 582. [Abstract] [Full Text] [PDF]

				D. Bunout, G. Barrera, L. Leiva, V. Gattas, M. P. de la Maza, F. Haschke, P. Steenhout, P. Klassen, C. Hager, E. Offord, et al. Effect of a Nutritional Supplementation on Bone Health in Chilean Elderly Subjects with Femoral Osteoporosis J. Am. Coll. Nutr., June 1, 2006; 25(3): 170 - 177. [Abstract] [Full Text] [PDF]

				C. M. Weaver and J. M. K. Cheong Soy Isoflavones and Bone Health: The Relationship Is Still Unclear J. Nutr., May 1, 2005; 135(5): 1243 - 1247. [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]

				L. Keinan-Boker, Y. T van der Schouw, D. E Grobbee, and P. H. Peeters Reply to M Messina Am. J. Clinical Nutrition, August 1, 2004; 80(2): 529 - 530. [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]

				K. D. Setchell and E. Lydeking-Olsen Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies Am. J. Clinical Nutrition, September 1, 2003; 78(3): 593S - 609. [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 Anderson, J. J. B. Articles by Garner, S. C. Search for Related Content PubMed PubMed Citation Articles by Anderson, J. J. B. Articles by Garner, S. C.