This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (252)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Nutritional and Metabolic Disorders  • Lipids and Lipid Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

John R. Crouse III, MD; Timothy Morgan, PhD; James G. Terry, MS; Julie Ellis, MPH; Mara Vitolins, DrPH; Gregory L. Burke, MD

Arch Intern Med. 1999;159:2070-2076.

Context  Isolated soy protein reduces plasma concentrations of total and low-density lipoprotein (LDL) cholesterol.

Objective  To identify the agent(s) responsible for the cholesterol-lowering effect of soy in mildly hypercholesterolemic volunteers: isoflavones isolated together with soy protein or soy protein itself.

Design  Double-blind randomized parallel trial.

Setting  Single-center study.

Participants  A total of 156 healthy men and women with LDL cholesterol levels between 3.62 mmol/L (140 mg/dL) and 5.17 mmol/L (200 mg/dL) after instruction in a National Cholesterol Education Program Step I diet and recruited by advertisement from the community.

Intervention  One of 5 daily diets (25 g of casein [for isoflavone-free comparison] or 25 g of isolated soy protein containing 3, 27, 37, or 62 mg of isoflavones).

Main Outcome Measures  Change and percent change from baseline in plasma concentrations of triglycerides and total, LDL, and high-density lipoprotein cholesterol after 9 weeks.

Results  Compared with casein, isolated soy protein with 62 mg of isoflavones lowered total and LDL cholesterol levels by 4% (P=.04) and 6% (P=.01), respectively. In patients with LDL cholesterol levels in the top half of the population studied (>4.24 mmol/L [>164 mg/dL]), comparable reductions were 9% (P<.001) and 10% (P=001), respectively; in this group, isolated soy protein with 37 mg of isoflavones reduced total (P=.007) and LDL (P=.02) cholesterol levels by 8%, and there was a dose-response effect of increasing amounts of isoflavones on total and LDL cholesterol levels. Plasma concentrations of triglycerides and high-density lipoprotein cholesterol were unaffected. Ethanol-extracted isolated soy protein containing 3 mg of isoflavones did not significantly reduce plasma concentrations of total or LDL cholesterol.

Conclusions  Naturally occurring isoflavones isolated with soy protein reduce the plasma concentrations of total and LDL cholesterol without affecting concentrations of triglycerides or high-density lipoprotein cholesterol in mildly hypercholesterolemic volunteers consuming a National Cholesterol Education Program Step I diet. Ethanol-extracted isolated soy protein did not significantly reduce plasma concentrations of total or LDL cholesterol.

From the Departments of Medicine (Dr Crouse, Mr Terry, and Ms Ellis), and Public Health Sciences (Drs Morgan, Vitolins, and Burke), Wake Forest University School of Medicine, Winston-Salem, NC.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke
Chan et al.
Eur Heart J 2008;29:2800-2807.
ABSTRACT | FULL TEXT  

Effect of Two Types of Soy Milk and Dairy Milk on Plasma Lipids in Hypercholesterolemic Adults: A Randomized Trial
Gardner et al.
J. Am. Coll. Nutr. 2007;26:669-677.
ABSTRACT | FULL TEXT  

Association of Dietary Intake of Soy, Beans, and Isoflavones With Risk of Cerebral and Myocardial Infarctions in Japanese Populations: The Japan Public Health Center Based (JPHC) Study Cohort I
Kokubo et al.
Circulation 2007;116:2553-2562.
ABSTRACT | FULL TEXT  

Proteomic biomarkers of peripheral blood mononuclear cells obtained from postmenopausal women undergoing an intervention with soy isoflavones
Fuchs et al.
Am. J. Clin. Nutr. 2007;86:1369-1375.
ABSTRACT | FULL TEXT  

A BRIEF COMMUNICATION: Subcutaneously Administrated Genistein and Daidzein Decrease Serum Cholesterol and Increase Triglyceride Levels in Male Middle-Aged Rats
Sosic-Jurjevic et al.
Exp. Biol. Med. 2007;232:1222-1227.
ABSTRACT | FULL TEXT  

Pasta Naturally Enriched with Isoflavone Aglycons from Soy Germ Reduces Serum Lipids and Improves Markers of Cardiovascular Risk
Clerici et al.
J. Nutr. 2007;137:2270-2278.
ABSTRACT | FULL TEXT  

Influence of inulin on plasma isoflavone concentrations in healthy postmenopausal women
Piazza et al.
Am. J. Clin. Nutr. 2007;86:775-780.
ABSTRACT | FULL TEXT  

Effect of Soy Nuts on Blood Pressure and Lipid Levels in Hypertensive, Prehypertensive, and Normotensive Postmenopausal Women
Welty et al.
Arch Intern Med 2007;167:1060-1067.
ABSTRACT | FULL TEXT  

Effect of soy protein from differently processed products on cardiovascular disease risk factors and vascular endothelial function in hypercholesterolemic subjects
Matthan et al.
Am. J. Clin. Nutr. 2007;85:960-966.
ABSTRACT | FULL TEXT  

Soy isoflavones lower serum total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials
Taku et al.
Am. J. Clin. Nutr. 2007;85:1148-1156.
ABSTRACT | FULL TEXT  

Dietary supplements in patients with cancer: Risks and key concepts, part 2
Michaud et al.
Am J Health Syst Pharm 2007;64:467-480.
ABSTRACT | FULL TEXT  

High Urinary Isoflavone Excretion Phenotype Decreases Plasma Cholesterol in Golden Syrian Hamsters Fed Soy Protein
Ye et al.
J. Nutr. 2006;136:2773-2778.
ABSTRACT | FULL TEXT  

Flavonoids Attenuate Cardiovascular Disease, Inhibit Phosphodiesterase, and Modulate Lipid Homeostasis in Adipose Tissue and Liver
Peluso
Exp. Biol. Med. 2006;231:1287-1299.
ABSTRACT | FULL TEXT  

Soy protein, isoflavones, and cardiovascular health: a summary of a statement for professionals from the american heart association nutrition committee.
Sacks et al.
Arterioscler. Thromb. Vasc. Bio. 2006;26:1689-1692.
FULL TEXT  

Diet and Lifestyle Recommendations Revision 2006: A Scientific Statement From the American Heart Association Nutrition Committee
Lichtenstein et al.
Circulation 2006;114:82-96.
ABSTRACT | FULL TEXT  

Phytoestrogens and Lipoproteins in Women
Bairey Merz et al.
J. Clin. Endocrinol. Metab. 2006;91:2209-2213.
ABSTRACT | FULL TEXT  

A Critical Evaluation of the Role of Soy Protein and Isoflavone Supplementation in the Control of Plasma Cholesterol Concentrations
Dewell et al.
J. Clin. Endocrinol. Metab. 2006;91:772-780.
ABSTRACT | FULL TEXT  

Soy Protein, Isoflavones, and Cardiovascular Health: An American Heart Association Science Advisory for Professionals From the Nutrition Committee
Sacks et al.
Circulation 2006;113:1034-1044.
ABSTRACT | FULL TEXT  

Effect of soy protein varying in isoflavone content on serum lipids in healthy young men
McVeigh et al.
Am. J. Clin. Nutr. 2006;83:244-251.
ABSTRACT | FULL TEXT  

Effect of Temperature and Soil Moisture Status during Seed Development on Soybean Seed Isoflavone Concentration and Composition
Lozovaya et al.
Crop Sci. 2005;45:1934-1940.
ABSTRACT | FULL TEXT  

Effect of Soy Protein Containing Isoflavones on Blood Lipids in Moderately Hypercholesterolemic Adults: A Randomized Controlled Trial
Ma et al.
J. Am. Coll. Nutr. 2005;24:275-285.
ABSTRACT | FULL TEXT  

Effect of Soybean Protein on Blood Pressure: A Randomized, Controlled Trial
He et al.
ANN INTERN MED 2005;143:1-9.
ABSTRACT | FULL TEXT  

Soy Protein Isolate Increases Hepatic Thyroid Hormone Receptor Content and Inhibits Its Binding to Target Genes in Rats
Huang et al.
J. Nutr. 2005;135:1631-1635.
ABSTRACT | FULL TEXT  

Isoflavone Profile and Antioxidant Activity of Brazilian Soybean Varieties
Genovese et al.
Food Science and Technology International 2005;11:205-211.
ABSTRACT  

The Effect of a Plant-Based Diet on Plasma Lipids in Hypercholesterolemic Adults: A Randomized Trial
Gardner et al.
ANN INTERN MED 2005;142:725-733.
ABSTRACT | FULL TEXT  

Longitudinal study of soy food intake and blood pressure among middle-aged and elderly Chinese women
Yang et al.
Am. J. Clin. Nutr. 2005;81:1012-1017.
ABSTRACT | FULL TEXT  

Soy Protein Isolates of Varying Isoflavone Content Exert Minor Effects on Serum Reproductive Hormones in Healthy Young Men
Dillingham et al.
J. Nutr. 2005;135:584-591.
ABSTRACT | FULL TEXT  

Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile
Zhan and Ho
Am. J. Clin. Nutr. 2005;81:397-408.
ABSTRACT | FULL TEXT  

Probiotic Consumption Does Not Enhance the Cholesterol-Lowering Effect of Soy in Postmenopausal Women
Greany et al.
J. Nutr. 2004;134:3277-3283.
ABSTRACT | FULL TEXT  

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
Rosell et al.
Am. J. Clin. Nutr. 2004;80:1391-1396.
ABSTRACT | FULL TEXT  

The Apparent Absorptions of Isoflavone Glucosides and Aglucons Are Similar in Women and Are Increased by Rapid Gut Transit Time and Low Fecal Isoflavone Degradation
Zheng et al.
J. Nutr. 2004;134:2534-2539.
ABSTRACT | FULL TEXT  

Soy Isoflavone Intake Lowers Serum LDL Cholesterol: A Meta-Analysis of 8 Randomized Controlled Trials in Humans
Zhuo et al.
J. Nutr. 2004;134:2395-2400.
ABSTRACT | FULL TEXT  

Effects of Isolated Isoflavonoids on Lipids, Lipoproteins, Insulin Sensitivity, and Ghrelin in Postmenopausal Women
Nikander et al.
J. Clin. Endocrinol. Metab. 2004;89:3567-3572.
ABSTRACT | FULL TEXT  

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
Atkinson et al.
J. Nutr. 2004;134:1759-1764.
ABSTRACT | FULL TEXT  

Dietary Soy Protein Isolate and Isoflavones Modulate Hepatic Thyroid Hormone Receptors in Rats
Xiao et al.
J. Nutr. 2004;134:743-749.
ABSTRACT | FULL TEXT  

Soy Protein Favorably Affects LDL Size Independently of Isoflavones in Hypercholesterolemic Men and Women
Desroches et al.
J. Nutr. 2004;134:574-579.
ABSTRACT | FULL TEXT  

Effects of Dietary Intake of Soy Protein and Isoflavones on Cardiovascular Disease Risk Factors in High Risk, Middle-Aged Men in Scotland
Sagara et al.
J. Am. Coll. Nutr. 2004;23:85-91.
ABSTRACT | FULL TEXT  

Regulation of apoA-I gene expression: mechanism of action of estrogen and genistein
Lamon-Fava and Micherone
J. Lipid Res. 2004;45:106-112.
ABSTRACT | FULL TEXT  

Proteins of White Lupin Seed, a Naturally Isoflavone-Poor Legume, Reduce Cholesterolemia in Rats and Increase LDL Receptor Activity in HepG2 Cells
Sirtori et al.
J. Nutr. 2004;134:18-23.
ABSTRACT | FULL TEXT  

Soy Protein With Isoflavones, but not an Isoflavone-Rich Supplement, Improves Arterial Low-Density Lipoprotein Metabolism and Atherogenesis
Wagner et al.
Arterioscler. Thromb. Vasc. Bio. 2003;23:2241-2246.
ABSTRACT | FULL TEXT  

Soy Protein With or Without Isoflavones, Soy Germ and Soy Germ Extract, and Daidzein Lessen Plasma Cholesterol Levels in Golden Syrian Hamsters
Song et al.
Exp. Biol. Med. 2003;228:1063-1068.
ABSTRACT | FULL TEXT  

Rapid Gut Transit Time and Slow Fecal Isoflavone Disappearance Phenotype Are Associated with Greater Genistein Bioavailability in Women
Zheng et al.
J. Nutr. 2003;133:3110-3116.
ABSTRACT | FULL TEXT  

Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women
Steinberg et al.
Am. J. Clin. Nutr. 2003;78:123-130.
ABSTRACT | FULL TEXT  

Treatment with Antibiotics Reduces Plasma Equol Concentration in Cynomolgus Monkeys (Macaca fascicularis)
Blair et al.
J. Nutr. 2003;133:2262-2267.
ABSTRACT | FULL TEXT  

Phytoestrogen Supplement Use by Women
Kurzer
J. Nutr. 2003;133:1983S-1986.
ABSTRACT | FULL TEXT  

Soy Isoflavones Exert Antidiabetic and Hypolipidemic Effects through the PPAR Pathways in Obese Zucker Rats and Murine RAW 264.7 Cells
Mezei et al.
J. Nutr. 2003;133:1238-1243.
ABSTRACT | FULL TEXT  

Dietary Flaxseed Meal is More Protective Than Soy Protein Concentrate Against Hypertriglyceridemia and Steatosis of the Liver in an Animal Model of Obesity
Bhathena et al.
J. Am. Coll. Nutr. 2003;22:157-164.
ABSTRACT | FULL TEXT  

Bioavailability, Disposition, and Dose-Response Effects of Soy Isoflavones When Consumed by Healthy Women at Physiologically Typical Dietary Intakes
Setchell et al.
J. Nutr. 2003;133:1027-1035.
ABSTRACT | FULL TEXT  

A Proteomic Investigation of Isolated Soy Proteins with Variable Effects in Experimental and Clinical Studies
Gianazza et al.
J. Nutr. 2003;133:9-14.
ABSTRACT | FULL TEXT  

References
Circulation 2002;106:3373-3421.
FULL TEXT  

Dietary Soy and Soy Isoflavones Have Gender-Specific Effects on Plasma Lipids and Isoflavones in Golden Syrian F1B Hybrid Hamsters
Blair et al.
J. Nutr. 2002;132:3585-3591.
ABSTRACT | FULL TEXT  

Role of Soy Protein in Cholesterol-Lowering: How Good Is It?
Nestel
Arterioscler. Thromb. Vasc. Bio. 2002;22:1743-1744.
FULL TEXT  

Lipoprotein Response to Diets High in Soy or Animal Protein With and Without Isoflavones in Moderately Hypercholesterolemic Subjects
Lichtenstein et al.
Arterioscler. Thromb. Vasc. Bio. 2002;22:1852-1858.
ABSTRACT | FULL TEXT  

Effects on the Human Serum Lipoprotein Profile of {beta}-Glucan, Soy Protein and Isoflavones, Plant Sterols and Stanols, Garlic and Tocotrienols
Kerckhoffs et al.
J. Nutr. 2002;132:2494-2505.
ABSTRACT | FULL TEXT  

Effects of high- and low-isoflavone soyfoods on blood lipids, oxidized LDL, homocysteine, and blood pressure in hyperlipidemic men and women
Jenkins et al.
Am. J. Clin. Nutr. 2002;76:365-372.
ABSTRACT | FULL TEXT  

Moderate intakes of intact soy protein rich in isoflavones compared with ethanol-extracted soy protein increase HDL but do not influence transforming growth factor {beta}1 concentrations and hemostatic risk factors for coronary heart disease in healthy subjects
Sanders et al.
Am. J. Clin. Nutr. 2002;76:373-377.
ABSTRACT | FULL TEXT  

Phytoestrogens and Cardiovascular Disease: Where's the Meat?
Anthony
Arterioscler. Thromb. Vasc. Bio. 2002;22:1245-1247.
FULL TEXT  

A High Isoflavone Soy Protein Diet and Intravenous Genistein Delay Rejection of Rat Cardiac Allografts
O'Connor et al.
J. Nutr. 2002;132:2283-2287.
ABSTRACT | FULL TEXT  

A comparison of the effects of 2 doses of soy protein or casein on serum lipids, serum lipoproteins, and plasma total homocysteine in hypercholesterolemic subjects
Tonstad et al.
Am. J. Clin. Nutr. 2002;76:78-84.
ABSTRACT | FULL TEXT  

Clinical nutrition: 7. Functional foods -- more than just nutrition
Jones
CMAJ 2002;166:1555-1563.
FULL TEXT  

The Scientific Evidence for a Beneficial Health Relationship Between Walnuts and Coronary Heart Disease
Feldman
J. Nutr. 2002;132:1062S-1101.
ABSTRACT | FULL TEXT  

Soy, Soy Phytoestrogens and Cardiovascular Disease
Clarkson
J. Nutr. 2002;132:566S-569.
ABSTRACT | FULL TEXT  

Estrogen replacement therapy, atherosclerosis, and vascular function
Mikkola and Clarkson
Cardiovasc Res 2002;53:605-619.
ABSTRACT | FULL TEXT  

Alcohol-Extracted, but Not Intact, Dietary Soy Protein Lowers Lipoprotein(a) Markedly
Meinertz et al.
Arterioscler. Thromb. Vasc. Bio. 2002;22:312-316.
ABSTRACT | FULL TEXT  

The Effects of Soy-Derived Phytoestrogens on Serum Lipids and Lipoproteins in Moderately Hypercholesterolemic Postmenopausal Women
Dewell et al.
J. Clin. Endocrinol. Metab. 2002;87:118-121.
ABSTRACT | FULL TEXT  

The Inhibitory Effect of Soy Protein Isolate on Atherosclerosis in Mice Does Not Require the Presence of LDL Receptors or Alteration of Plasma Lipoproteins
Adams et al.
J. Nutr. 2002;132:43-49.
ABSTRACT | FULL TEXT  

Soy for Breast Cancer Survivors: A Critical Review of the Literature
Messina and Loprinzi
J. Nutr. 2001;131:3095S-3108.
ABSTRACT | FULL TEXT  

Soy Isoflavones--Benefits and Risks from Nature's Selective Estrogen Receptor Modulators (SERMs)
Setchell
J. Am. Coll. Nutr. 2001;20:354S-362.
ABSTRACT | FULL TEXT  

Soy Protein Intake by Perimenopausal Women Does Not Affect Circulating Lipids and Lipoproteins or Coagulation and Fibrinolytic Factors
Dent et al.
J. Nutr. 2001;131:2280-2287.
ABSTRACT | FULL TEXT  

Got soy?
Lichtenstein
Am. J. Clin. Nutr. 2001;73:667-668.
FULL TEXT  

The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women
Gardner et al.
Am. J. Clin. Nutr. 2001;73:728-735.
ABSTRACT | FULL TEXT  

Bioavailability of Pure Isoflavones in Healthy Humans and Analysis of Commercial Soy Isoflavone Supplements
Setchell et al.
J. Nutr. 2001;131:1362S-1375.
ABSTRACT | FULL TEXT  

What Do We Need to Know about Active Ingredients in Dietary Supplements? Summary of Workshop Discussion
Hendrich and Fisher
J. Nutr. 2001;131:1387S-1388.
FULL TEXT  

Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women
Wangen et al.
Am. J. Clin. Nutr. 2001;73:225-231.
ABSTRACT | FULL TEXT  

Ethanol-Extracted Soy Protein Isolate Does Not Modulate Serum Cholesterol in Golden Syrian Hamsters: A Model of Postmenopausal Hypercholesterolemia
Lucas et al.
J. Nutr. 2001;131:211-214.
ABSTRACT | FULL TEXT  

Inhibition of Postmenopausal Atherosclerosis Progression: A Comparison of the Effects of Conjugated Equine Estrogens and Soy Phytoestrogens
Clarkson et al.
J. Clin. Endocrinol. Metab. 2001;86:41-47.
ABSTRACT | FULL TEXT  

AHA Scientific Statement: AHA Dietary Guidelines: Revision 2000: A Statement for Healthcare Professionals From the Nutrition Committee of the American Heart Association
Krauss et al.
J. Nutr. 2001;131:132-146.
FULL TEXT  

Soy Protein and Cardiovascular Disease : A Statement for Healthcare Professionals From the Nutrition Committee of the AHA
Erdman
Circulation 2000;102:2555-2559.
FULL TEXT  

AHA Dietary Guidelines : Revision 2000: A Statement for Healthcare Professionals From the Nutrition Committee of the American Heart Association
Krauss et al.
Stroke 2000;31:2751-2766.
FULL TEXT  

AHA Dietary Guidelines : Revision 2000: A Statement for Healthcare Professionals From the Nutrition Committee of the American Heart Association
Krauss et al.
Circulation 2000;102:2284-2299.
FULL TEXT  

Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women
Merz-Demlow et al.
Am. J. Clin. Nutr. 2000;71:1462-1469.
ABSTRACT | FULL TEXT  

Effects of feeding 4 levels of soy protein for 3 and 6 wk on blood lipids and apolipoproteins in moderately hypercholesterolemic men
Teixeira et al.
Am. J. Clin. Nutr. 2000;71:1077-1084.
ABSTRACT | FULL TEXT  

Soy and Cardiovascular Disease: Cholesterol Lowering and Beyond
Anthony
J. Nutr. 2000;130:662-662.
FULL TEXT  

Oral Presentation Abstracts
J. Nutr. 2000;130:666-666.
FULL TEXT  

Plant Sterols, Health Claims and Strategies to Reduce Cardiovascular Disease Risk
Jenkins and Kendall
J. Am. Coll. Nutr. 1999;18:559-562.
FULL TEXT