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

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Sanders, T. A. Articles by Wiseman, H. Search for Related Content PubMed PubMed Citation Articles by Sanders, T. A. Articles by Wiseman, H. Agricola Articles by Sanders, T. A. Articles by Wiseman, H.

Moderate intakes of intact soy protein rich in isoflavones compared with ethanol-extracted soy protein increase HDL but do not influence transforming growth factor ß₁ concentrations and hemostatic risk factors for coronary heart disease in healthy subjects^1,2,3

¹ From the Nutrition, Food and Health Research Centre, King’s College London, London (TABS, TSD, and HW); the Department of Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (DG); and the Medical Research Council Epidemiology and Medical Care Unit, Wolfson Institute, St Bartholomew’s and the Royal London School of Medicine and Dentistry, London (GJM).

² Supported by a grant from the International Foundation for Nutrition Research and Education.

³ Address reprint requests to TAB Sanders, Nutrition, Food and Health Research Centre, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NN, United Kingdom. E-mail: tom.sanders{at}kcl.ac.uk.

	ABSTRACT

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Background: Soybeans contain estrogenic isoflavones that may influence plasma concentrations of transforming growth factor ß₁ (TGF-ß₁) and plasma lipid and hemostatic risk factors for coronary heart disease.

Objective: We compared the effects of moderate intakes of soy protein containing intact phytoestrogens (high-isoflavone diet) and soy protein from which most of the phytoestrogens had been extracted (low-isoflavone diet) on active TGF-ß₁ concentrations and plasma lipid and hemostatic risk factors for coronary heart disease.

Design: A randomized crossover trial was conducted in 22 young, healthy, normolipidemic subjects (5 men and 17 women) who consumed diets providing 56 or 2 mg isoflavones/d for 17 d each with a 25-d washout period between treatments. Fasting blood samples were obtained on days 13 and 14 of each treatment to measure plasma isoflavone, lipid, fibrinogen, and active TGF-ß₁ concentrations and factor VII coagulant and plasminogen activator inhibitor type 1 activities.

Results: Plasma isoflavone concentrations were 100–999 times greater after the high-isoflavone diet than after the low-isoflavone diet (P < 0.05). Plasma HDL-cholesterol and apolipoprotein A-I concentrations were 4% (95% CI: 1%, 8%) and 6% (95% CI: 3%, 10%) higher, respectively, after the high-isoflavone diet than after the low-isoflavone diet (P < 0.01 for both).

Conclusion: Compared with soy protein from which most of the phytoestrogens have been extracted, soy protein with intact phytoestrogens increases HDL-cholesterol and apolipoprotein A-I concentrations but does not influence LDL-cholesterol, TGF-ß₁, or fibrinogen concentrations; factor VII coagulant activity; or plasminogen activator inhibitor type 1 activity in normolipidemic, healthy subjects.

Key Words: Isoflavones • phytoestrogens • genistein • transforming growth factor ß 1 • plasma lipids • lipoproteins • factor VII coagulant • fibrinogen • plasminogen activator inhibitor • soy • coronary heart disease • coronary artery disease

	INTRODUCTION

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
The favorable effect of soy products on the ratio of plasma LDL- to HDL-cholesterol concentrations (1) may be attributable to the isoflavone phytoestrogens, in particular genistein and daidzein, in soy. Rhesus monkeys fed diets containing 200 g intact soy protein isolate/kg diet had lower LDL-cholesterol and higher HDL-cholesterol concentrations compared with animals fed the same amount of soy protein from which most of the isoflavones had been extracted (2). In addition, male cynomolgus macaques fed moderately atherogenic diets developed smaller atherosclerotic lesions during a diet containing more phytoestrogens (3). The phytoestrogens in soy may have effects that are similar to those of estradiol, which increases LDL receptor expression and decreases hepatic lipase activity (4). Alternatively, atheroprotection might involve modulating (5,6) the fraction of the cytokine transforming growth factor ß₁ (TGF-ß₁) circulating in the active form, which is involved in the maintenance of normal architecture of the blood vessel wall.

A recent report (7) showed that transdermal 17 ß-estradiol increases latent TGF-ß₁ concentrations in postmenopausal women. Several mechanisms by which estrogenic compounds may influence active TGF-ß₁ concentrations have been identified. For example, a reduction in the concentration of triacylglycerol-rich lipoproteins, into which active TGF-ß₁ is sequestered, might increase active TGF-ß₁ concentrations. Alternatively, estrogenic compounds may stimulate production of the latent TGF-ß₁ precursor, either at the transcriptional level or the post-transcriptional level, as reported previously for tamoxifen (8). Studies in cell culture suggest that genistein may inhibit cell growth by modulating TGF-ß₁ signaling pathways (9), but to date there have been no reports about the effect of soy on TGF-ß₁ in humans.

Estrogenic compounds may be atheroprotective, but they also increase the risk of arterial thrombosis. Elevated plasma fibrinogen concentration and factor VII coagulant (FVII:c) activity and decreased fibrinolytic activity, which is associated with increased plasminogen activator inhibitor type 1 (PAI-1) activity (10), are independent risk factors for CHD (11). Oral estrogens increase FVII:c activity (12–14) and decrease PAI-1 activity (15). The proteolytic action of plasmin activates TGF-ß₁, and consequently PAI-1 activity may decrease active TGF-ß₁ concentrations. Oral estrogens can increase plasma fibrinogen concentrations, especially in smokers (16), but low-dose oral estrogens show minimal effects on plasma fibrinogen concentrations (2,13,15). One human study found increased concentrations of activated FVII after consumption of a fermented soy product (17). No other studies have examined the effect of soy phytoestrogens on these hemostatic variables. The aim of the present study was to ascertain whether soy phytoestrogens, when consumed as soy protein, have significant effects on these CHD risk factors in healthy young men and women.

	SUBJECTS AND METHODS

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Subjects
Twenty-four healthy men and women were recruited from among the staff and alumni of King’s College London and from British Industries Biological Research Association International. The exclusion criteria included body mass index (in kg/m²) < 18 or > 30; cigarette smoking; hyperlipidemia (plasma cholesterol > 6.5 mmol/L or plasma triacylglycerol > 3.0 mmol/L); history of cholestatic liver disease, gastrointestinal disease, pancreatitis, diabetes mellitus, or myocardial infarction; use of antihypertensive or lipid-lowering medication; and use of antibiotics within the previous 6 mo. Before a subject was enrolled, we confirmed that his or her fasting plasma lipoprotein lipid concentrations, body weight, blood cell count, and liver function were within prescribed limits. Women had a urinary pregnancy test to confirm that they were not pregnant.

Complete data were obtained from 22 of the 24 subjects initially recruited. Two subjects withdrew from the study because one was prescribed antibiotics for an ear infection, which violated the study protocol, and the other withdrew for personal reasons. The 22 subjects included 17 women and 5 men; the mean (± SD) age was 30 ± 7.7 y and the mean body mass index was 22.0 ± 2.7. At baseline, mean (± SD) plasma cholesterol and triacylglycerol concentrations were 4.8 ± 0.82 and 1.1 ± 0.55 mmol/L, respectively.

Study design and treatments
The study had a randomized crossover design. The treatments consisted of textured soy protein concentrates that were either low in isoflavones (2 mg/d) or high in isoflavones (56 mg/d), as supplied by Solbar Hatzor Ltd, Ashdod, Israel. Isoflavones had been extracted from the low-isoflavone soy protein concentrate with a mixture of food-grade alcohol (700 g/L or 70%) and water. After extraction, no remaining alcohol was detected (limit of detection, 0.1 g/L). The low-isoflavone and high-isoflavone soy protein concentrates contained 698 and 548 g protein/kg, respectively. The textured soy protein was made into vegetarian burgers, and subjects were asked to consume one burger daily during the study period. Both types of burger supplied 0.8 MJ, 15 g protein, 9 g fat, and 10 g carbohydrate. On analysis, the high-isoflavone burger contained 21.2 mg (129 µmol) daidzein and 34.8 mg (84 µmol) genistein and the low-isoflavone burger contained 0.9 mg (3.5 µmol) daidzein and 1.0 mg (3.7 µmol) genistein. Each treatment period lasted 17 d, and the 2 treatment periods were separated by a washout period of 25 d.

The subjects were instructed to avoid all other soy products, legumes, and Quorn products throughout the study. They were also asked to make no changes in their lifestyle, including their usual exercise habits and diet, other than those changes necessary for compliance with the study. The subjects were asked to keep a 3-d weighed food record to assess their nutrient intake. Nutrient analysis of the food records was carried out by using the COMPEAT 4 PROGRAMME (version 4; Nutrition Systems, London).

Blood samples were obtained on days 13 and 14 of each treatment period. The personnel analyzing the blood samples were blinded to the treatment allocation. The subjects were also blinded to the allocation of treatment, but the nutritionist (TSD) involved in preparing and providing the soy burgers was not. The subjects received a modest payment for taking part in the study. The study protocol was reviewed and approved by the Research Ethics Committee of King’s College London, and all participants gave their written, informed consent.

Collection, handling, and analysis of blood samples
When subjects were fasting, venous blood samples were collected into evacuated tubes by using the minimal amount of compression necessary to display the vein. The first 4.5 mL of blood was drawn into a tube containing EDTA. Plasma was then separated by centrifugation (1500 x g at 4 °C for 15 min) and stored at -20 °C until determination of plasma lipids and lipoproteins. For determination of plasma fibrinogen, FVII:c, and PAI-1, 4.5 mL blood was collected into 0.5 mL trisodium citrate solution (38 g/L) at room temperature and centrifuged at 1500 x g for 15 min at 20 °C. Blood for the TGF-ß₁ assay was collected into pre-cooled tubes (Diatube H; Becton Dickinson, Vacutainer Systems, Plymouth, United Kingdom) and centrifuged within 30 min of blood collection (700 x g at 4 °C for 15 min). The middle layer of plasma was collected and recentrifuged under the same conditions to minimize platelet contamination. Blood for the isoflavone analyses was collected into evacuated tubes containing lithium heparin and the plasma was separated by centrifugation (1500 x g at 22 °C for 20 min) and frozen. All plasma samples were snap frozen in liquid nitrogen and stored at -70 °C until analyzed.

Laboratory methods
Plasma isoflavone concentrations were determined with gas chromatography–mass spectrometry and were reported previously (18). Total, HDL-, and LDL-cholesterol and triacylglycerol concentrations were measured with fully enzymatic procedures. Plasma concentrations of apolipoproteins A-I, A-II, and B were measured with immunoturbidimetry as described previously (19). Plasma fibrinogen concentration and FVII:c and PAI-1 activities were determined by the MRC Epidemiology and Medical Care Unit with a method described previously (19). Active TGF-ß₁ concentrations were determined with a capture assay subject to assumptions described previously (20). All samples were analyzed blind in a single batch to avoid between-run variation.

Statistical analyses
SPSS/PC version 8.0 (SPSS Inc, Chicago) was used for all statistical analyses. The study had a 90% power to detect a 0.7 within-subject SD unit change in the variables under consideration at P < 0.05. On the basis of previous studies, this had sufficient power to detect differences of 5% in FVII:c activity and fibrinogen concentration. No data were available to estimate the within-subject SD for TGF-ß₁. The values for day 13 and day 14 of each treatment period were averaged, and comparisons between treatments were then made by using paired t tests. The Wilcoxon test was used to compare values for TGF-ß₁.

	RESULTS

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
The subjects’ reported food intakes during the 2 dietary treatments are shown in Table 1. The proportion of energy derived from fat was slightly higher during the high-isoflavone diet than during the low-isoflavone diet (P < 0.05). Otherwise, there were no significant differences in dietary intakes, and the subjects’ body weights were stable. The plasma isoflavone concentrations after the 2 dietary treatments are shown in Figure 1. After the high-isoflavone diet, these concentrations were markedly higher (P < 0.01 for genistein and daidzein and P < 0.05 for equol) than after the low-isoflavone diet.

View larger version (11K): [in this window] [in a new window]   FIGURE 1. . Mean (with 95% CIs) plasma isoflavone concentrations after the low-isoflavone diet () and high-isoflavone diet () in 22 subjects. The mean equol concentration after the low-isoflavone diet was 2 ± 2 nmol/L (bar is not visible). Isoflavone concentrations were significantly higher after the high-isoflavone diet than after the low-isoflavone diet, *P < 0.05, **P < 0.01.

	DISCUSSION

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

The proportion of soy protein in the study diets was about 5 times lower than the proportions used in primate studies (2,3). However, the amount used in the present study approximates the highest amount that human subjects could be expected to consume on a regular basis. With these intakes, there was no evidence of reduction in either LDL-cholesterol or apolipoprotein B concentrations. A recent study found that in hypercholesterolemic postmenopausal women, a higher intake of soy protein (as soy milk, providing 80 mg isoflavones/d) led to a reduction in LDL-cholesterol concentrations compared with a lower intake of a similar soy product from which the isoflavones had been extracted (21). However, in that study, the LDL-cholesterol concentrations during the treatment containing isoflavones did not differ significantly from those during the control period when the subjects consumed cow milk.

In one study, treatment with oral estradiol resulted in higher plasma triacylglycerol concentrations (12), but in the present study, the phytoestrogens were not associated with any such effect. Crouse et al (22) reported a significant trend in which HDL-cholesterol concentrations increased in overweight hypercholesterolemic men and women after consumption of 25 g soy protein containing 62 mg isoflavones, but Gardner et al (21) found no significant effect in overweight postmenopausal women. In the present study, consumption of 15 g soy protein containing 56 mg isoflavones/d resulted in 4% and 6% higher HDL-cholesterol and apolipoprotein A-I concentrations, respectively, compared with consumption of soy protein containing 2 mg isoflavones/d.

It is possible that the effects of dietary isoflavones on HDL-cholesterol concentrations may differ between normal-weight and overweight subjects. Genistein was found to stimulate apolipoprotein A-I synthesis by cultured human hepatoma cells in a manner similar to that of estradiol (23). Consequently, the increase in apolipoprotein A-I concentrations could be used as a biomarker for the estrogenic effects of isoflavones. We reported previously that plasma isoprostane concentrations and susceptibility of LDL cholesterol to oxidation were lower in these same subjects, and this may be related to the observed increase in HDL-cholesterol concentrations (24).

This is the first controlled study to measure the effects of soy isoflavones on active TGF-ß₁ concentrations and hemostatic risk factors for CHD (fibrinogen concentrations and FVII:c and PAI-1 activities). This study did not show any influence of soy isoflavones on these variables. The study had a statistical power that was high enough to detect a 0.7 change in within-subject SD, and the between-subject SD for TGF-ß₁ was 7.6 µg/L but the within-subject SD was 0.37 µg/L. Consequently, it is unlikely that an effect was missed because of a lack of statistical power. A limitation of the present study is that it was conducted in normolipidemic subjects. Grainger et al (25) suggested that hyperlipidemia and reduced TGF-ß₁ concentrations act synergistically to cause atherosclerosis, at least in mice. Consequently, the lack of effect of isoflavones in our study might be because the subjects had normal plasma concentrations of active TGF-ß₁ and normal lipid profiles. Another possible explanation is that much higher intakes of isoflavones might be required to exert an effect. It is plausible that isoflavones might affect TGF-ß₁ concentrations in older individuals with either abnormal concentrations of TGF-ß₁ or moderate hyperlipidemia, but further studies will be needed to resolve this issue.

	REFERENCES

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 

1. 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.[Abstract/Free Full Text]
2. Anthony MS, Clarkson TB, Hughes CL Jr, Morgan TM, Burke GL. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. J Nutr 1996;126:43–50.
3. Anthony MS, 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.[Abstract/Free Full Text]
4. Crook D, Seed M. Endocrine control of plasma lipoprotein metabolism: effects of gonadal steroids. Baillieres Clin Endocrinol Metab 1990;4:851–75.[Medline]
5. Grainger DJ, Witchell CM, Metcalfe JC. Tamoxifen elevates transforming growth factor-beta and suppresses diet-induced formation of lipid lesions in mouse aorta. Nat Med 1995;1:1067–73.[Medline]
6. Williams JK, Anthony MS, Honore EK, et al. Regression of atherosclerosis in female monkeys. Arterioscler Thromb Vasc Biol 1995;15:827–36.[Abstract/Free Full Text]
7. Djurovic S, Os I, Hofstad AE, Abdelonoor M, Westheim A, Berg K. Increased plasma concentrations of TGF-beta1 after hormone replacement therapy. J Intern Med 2000;247:279–85.[Medline]
8. Grainger DJ, Weissberg PL, Metcalfe JC. Tamoxifen decreases the rate of proliferation of rat vascular smooth-muscle cells in culture by inducing production of transforming growth factor beta. Biochem J 1993;294:109–12.
9. Kim H, Peterson TG, Barnes S. Mechanisms of action of the soy isoflavone genistein: emerging role for its effects via transforming growth factor ß signaling pathways. Am J Clin Nutr 1998;68(suppl):1418S–25S.[Abstract]
10. MacCallum PK, Cooper JA, Howarth DJ, Meade TW, Miller GJ. Sex differences in the determinants of fibrinolytic activity. Thromb Haemost 1998;79:587–90.[Medline]
11. Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993;342:1076–9.[Medline]
12. Randomised comparison of oestrogen versus oestrogen plus progestogen hormone replacement therapy in women with hysterectomy. Medical Research Council’s General Practice Research Framework. BMJ 1996;312:473–8.[Abstract/Free Full Text]
13. Norris LA, Bonnar J. Haemostatic changes and the oral contraceptive pill. Baillieres Clin Obstet Gynaecol 1997;11:545–64.[Medline]
14. Scarabin PY, Plu-Bureau, Zitoun D, Bara L, Guize L, Samama MM. Changes in haemostatic variables induced by oral contraceptives containing 50 micrograms or 30 micrograms oestrogen: absence of dose-dependent effect on PAI-1 activity. Thromb Haemost 1995;74:928–32.[Medline]
15. Scarabin PY, Alhenc-Gelas M, Plu-Bureau, Taisne P, Agher R, Aiach M. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arterioscler Thromb Vasc Biol 1997;17:3071–8.[Abstract/Free Full Text]
16. World Health Organization. A multicentre study of coagulation and haemostatic variables during oral contraception: variations with four formulations. Task Force on Oral Contraceptives, WHO Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland. Br J Obstet Gynaecol 1991;98:1117–28.[Medline]
17. Sakata T, Kario K, Asada R, et al. Increased activated factor VII levels caused by intake of natto, a Japanese vitamin K-rich food prepared from fermented soybean. Blood Coagul Fibrinolysis 1997;8:533–4.[Medline]
18. Rowland IR, Wiseman H, Sanders TA, 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.[Medline]
19. Sanders TA, Oakley FR, Miller GJ, Mitropoulos KA, Crook D, Oliver MF. Influence of n-6 versus n-3 polyunsaturated fatty acids in diets low in saturated fatty acids on plasma lipoproteins and hemostatic factors. Arterioscler Thromb Vasc Biol 1997;17:3449–60.[Abstract/Free Full Text]
20. Grainger DJ, Mosedale DE, Metcalfe JC, Weissberg PL, Kemp PR. Active and acid-activatable TGF-beta in human sera, platelets and plasma. Clin Chim Acta 1995;235:11–31.[Medline]
21. Gardner CD, Newell KA, Cherin R, Haskell WL. The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. Am J Clin Nutr 2001;73:728–35.[Abstract/Free Full Text]
22. Crouse JR III, 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.[Abstract/Free Full Text]
23. Lamon-Fava S. Genistein activates apolipoprotein A-I gene expression in the human hepatoma cell line hep G2. J Nutr 2000;130:2489–92.[Abstract/Free Full Text]
24. Wiseman H, O’Reilly JD, Adlercreutz H, et al. Isoflavone phytoestrogens consumed in soy decrease F(2)-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans. Am J Clin Nutr 2000;72:395–400.[Abstract/Free Full Text]
25. Grainger DJ, Mosedale DE, Metcalfe JC, Bottinger EP. Dietary fat and reduced levels of TGFbeta1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions. J Cell Sci 2000;113:2355–61.[Abstract]

This article has been cited by other articles:

				L. Djousse and J. M. Gaziano Breakfast Cereals and Risk of Heart Failure in the Physicians' Health Study I Arch Intern Med, October 22, 2007; 167(19): 2080 - 2085. [Abstract] [Full Text] [PDF]

				J. W. Erdman Jr., D. Balentine, L. Arab, G. Beecher, J. T. Dwyer, J. Folts, J. Harnly, P. Hollman, C. L. Keen, G. Mazza, et al. Flavonoids and Heart Health: Proceedings of the ILSI North America Flavonoids Workshop, May 31-June 1, 2005, Washington, DC J. Nutr., March 1, 2007; 137(3): 718S - 737S. [Abstract] [Full Text] [PDF]

				F. M. Sacks, A. Lichtenstein, L. Van Horn, W. Harris, P. Kris-Etherton, M. Winston, and for the AHA Nutrition Committee Soy protein, isoflavones, and cardiovascular health: a summary of a statement for professionals from the american heart association nutrition committee. Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1689 - 1692. [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]

				F. M. Sacks, A. Lichtenstein, L. Van Horn, W. Harris, P. Kris-Etherton, M. Winston, and for the American Heart Association Nutrition Commi Soy Protein, Isoflavones, and Cardiovascular Health: An American Heart Association Science Advisory for Professionals From the Nutrition Committee Circulation, February 21, 2006; 113(7): 1034 - 1044. [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]

				B. L. Dillingham, B. L. McVeigh, J. W. Lampe, and A. M. Duncan Soy Protein Isolates of Varying Isoflavone Content Exert Minor Effects on Serum Reproductive Hormones in Healthy Young Men J. Nutr., March 1, 2005; 135(3): 584 - 591. [Abstract] [Full Text] [PDF]

				S. Vega-Lopez, K.-J. Yeum, J. L Lecker, L. M Ausman, E. J Johnson, S. Devaraj, I. Jialal, and A. H Lichtenstein Plasma antioxidant capacity in response to diets high in soy or animal protein with or without isoflavones Am. J. Clinical Nutrition, January 1, 2005; 81(1): 43 - 49. [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]

				X.-G. Zhuo, M. K. Melby, and S. Watanabe Soy Isoflavone Intake Lowers Serum LDL Cholesterol: A Meta-Analysis of 8 Randomized Controlled Trials in Humans J. Nutr., September 1, 2004; 134(9): 2395 - 2400. [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]

				H. E Theobald, P. J Chowienczyk, R. Whittall, S. E Humphries, and T. A. Sanders LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and women Am. J. Clinical Nutrition, April 1, 2004; 79(4): 558 - 563. [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]

				S. Lamon-Fava and D. Micherone Regulation of apoA-I gene expression: mechanism of action of estrogen and genistein J. Lipid Res., January 1, 2004; 45(1): 106 - 112. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Sanders, T. A. Articles by Wiseman, H. Search for Related Content PubMed PubMed Citation Articles by Sanders, T. A. Articles by Wiseman, H. Agricola Articles by Sanders, T. A. Articles by Wiseman, H.