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 (121)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in JAMA  Topic Collections  • Nutritional and Metabolic Disorders  • Lipids and Lipid Disorders  • Women's Health  • Women's Health, Other  • Randomized Controlled Trial  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Controlled Trial

Sanne Kreijkamp-Kaspers, MD, PhD; Linda Kok, MD, PhD; Diederick E. Grobbee, MD, PhD; Edward H. F. de Haan, PhD; André Aleman, PhD; Johanna W. Lampe, PhD, RD; Yvonne T. van der Schouw, PhD

JAMA. 2004;292:65-74.

Context  Postmenopausal estrogen therapy has been posited to have some beneficial effects on aging processes, but its use has risks. Isoflavones, estrogenlike compounds naturally occurring in plant foods, might confer positive effects with fewer adverse effects.

Objective  To investigate whether soy protein with isoflavones improves cognitive function, bone mineral density, and plasma lipids in postmenopausal women.

Design, Setting, and Participants  Double-blind, randomized, placebo-controlled trial of 202 healthy postmenopausal women aged 60 to 75 years, recruited from a population-based sample in the Netherlands, conducted between April 2000 and September 2001.

Intervention  Participants were randomly assigned to receive 25.6 g of soy protein containing 99 mg of isoflavones (52 mg genistein, 41 mg daidzein, and 6 mg glycetein or total milk protein as a powder on a daily basis for 12 months.

Main Outcome Measures  Cognitive function was assessed using the following instruments: dementia, Mini-Mental State Examination; memory, Rey Auditory Verbal Learning Test, immediate recall, delayed recall, and recognition, the Digit Span forward and reversed, and the Doors test; complex attention tasks, Digit Symbol Substitution and Trailmaking, A1, A2, and B; and verbal skills, Verbal Fluency A and N, animals and occupations, and the Boston Naming Task. Bone mineral density of the hip and lumbar spine was assessed using dual-energy x-ray absorptiometry scanning. Lipid assessment included lipoprotein(a), total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides.

Results  A total of 175 women completed the baseline and at least 1 postintervention analysis and were included in the modified intent-to-treat analysis. Adherence was good (median plasma genistein levels, 17.2 and 615.1 nmol/L for placebo and soy group, respectively). Cognitive function, bone mineral density, or plasma lipids did not differ significantly between the groups after a year.

Conclusion  This double-blind randomized trial does not support the hypothesis that the use of soy protein supplement containing isoflavones improves cognitive function, bone mineral density, or plasma lipids in healthy postmenopausal women when started at the age of 60 years or later.

Author Affiliations: The Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht (Drs Kreijkamp-Kaspers, Kok, Grobbee, and van der Schouw), Division of Psychonomics, Helmholz Research Institute, Utrecht University (Dr de Haan), and Department of Neuroscience, University Medical Center Utrecht (Dr Aleman), Utrecht, the Netherlands; and Fred Hutchinson Cancer Research Center, Seattle, Wash (Dr Lampe).

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

RELATED LETTERS

Isoflavones and Postmenopausal Women
D. Lee Alekel
JAMA. 2004;292(19):2336.
EXTRACT | FULL TEXT  

Isoflavones and Postmenopausal Women
Cesare R. Sirtori
JAMA. 2004;292(19):2336-2337.
EXTRACT | FULL TEXT  

Isoflavones and Postmenopausal Women
Dave N. Muanza, Alex Vasquez, John Cannell, and William P. Grant
JAMA. 2004;292(19):2337.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The Metabolic Syndrome: Definition, Global Impact, and Pathophysiology
Potenza and Mechanick
Nutr Clin Pract 2009;24:560-577.
ABSTRACT | FULL TEXT  

Antiresorptive Effects of Phytoestrogen Supplements Compared with Estradiol or Risedronate in Postmenopausal Women Using 41Ca Methodology
Weaver et al.
J. Clin. Endocrinol. Metab. 2009;94:3798-3805.
ABSTRACT | FULL TEXT  

Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial
Kenny et al.
Am. J. Clin. Nutr. 2009;90:234-242.
ABSTRACT | FULL TEXT  

A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women
Gleason et al.
Age Ageing 2009;38:86-93.
ABSTRACT | FULL TEXT  

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  

Soy Protein Containing Isoflavones and Mammographic Density in a Randomized Controlled Trial in Postmenopausal Women
Verheus et al.
Cancer Epidemiol. Biomarkers Prev. 2008;17:2632-2638.
ABSTRACT | FULL TEXT  

Addition of Fructooligosaccharides and Dried Plum to Soy-based Diets Reverses Bone Loss in the Ovariectomized Rat
Johnson et al.
Evid Based Complement Alternat Med 2008;0:nen050v1-nen050.
ABSTRACT | FULL TEXT  

Docosahexaenoic Acid and 17{beta}-Estradiol Co-Treatment Is More Effective Than 17{beta}-Estradiol Alone in Maintaining Bone Post-Ovariectomy
Poulsen et al.
Exp. Biol. Med. 2008;233:592-602.
ABSTRACT | FULL TEXT  

Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: a randomized, double-blind, placebo controlled study
Brink et al.
Am. J. Clin. Nutr. 2008;87:761-770.
ABSTRACT | FULL TEXT  

Influence of Lifelong Soy Isoflavones Consumption on Bone Mass in the Rat
Mardon et al.
Exp. Biol. Med. 2008;233:229-237.
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 Do Not Affect Bone Resorption in Postmenopausal Women: A Dose-Response Study Using a Novel Approach with 41Ca
Cheong et al.
J. Clin. Endocrinol. Metab. 2007;92:577-582.
ABSTRACT | FULL TEXT  

Regulation of HOXA10 expression by phytoestrogens
Akbas et al.
Am. J. Physiol. Endocrinol. Metab. 2007;292:E435-E442.
ABSTRACT | FULL TEXT  

Genistein Affects Adipose Tissue Deposition in a Dose-Dependent and Gender-Specific Manner
Penza et al.
Endocrinology 2006;147:5740-5751.
ABSTRACT | FULL TEXT  

Complementary and Alternative Therapies for the Management of Dyslipidemia
Nies et al.
The Annals of Pharmacotherapy 2006;40:1984-1992.
ABSTRACT | FULL TEXT  

Summary of American Heart Association Diet and Lifestyle Recommendations Revision 2006
Lichtenstein et al.
Arterioscler. Thromb. Vasc. Bio. 2006;26:2186-2191.
FULL TEXT  

Thematic review series: Patient-Oriented Research. Dietary fat, carbohydrate, and protein: effects on plasma lipoprotein patterns
Lichtenstein
J. Lipid Res. 2006;47:1661-1667.
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  

Effect of a Nutritional Supplementation on Bone Health in Chilean Elderly Subjects with Femoral Osteoporosis
Bunout et al.
J. Am. Coll. Nutr. 2006;25:170-177.
ABSTRACT | FULL TEXT  

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

Metabolic Phenotype of Isoflavones Differ among Female Rats, Pigs, Monkeys, and Women
Gu et al.
J. Nutr. 2006;136:1215-1221.
ABSTRACT | FULL TEXT  

Natural Health Products in the Prevention and Treatment of Osteoporosis: Systematic Review of Randomized Controlled Trials
Whelan et al.
The Annals of Pharmacotherapy 2006;40:836-849.
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  

Update in Women's Health
Crandall and Pregler
ANN INTERN MED 2005;143:823-829.
FULL TEXT  

Prospective Cohort Study of Soy Food Consumption and Risk of Bone Fracture Among Postmenopausal Women
Zhang et al.
Arch Intern Med 2005;165:1890-1895.
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  

Integrating Complementary Medicine Into Cardiovascular Medicine: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (Writing Committee to Develop an Expert Consensus Document on Complementary and Integrative Medicine)
Vogel et al.
J Am Coll Cardiol 2005;46:184-221.
FULL TEXT  

SPECIES- AND DISPOSITION MODEL-DEPENDENT METABOLISM OF RALOXIFENE IN GUT AND LIVER: ROLE OF UGT1A10
Jeong et al.
Drug Metab. Dispos. 2005;33:785-794.
ABSTRACT | FULL TEXT  

Lipid Response to a Low-Fat Diet with or without Soy Is Modified by C-Reactive Protein Status in Moderately Hypercholesterolemic Adults
Hilpert et al.
J. Nutr. 2005;135:1075-1079.
ABSTRACT | FULL TEXT  

Higher Dietary Intake of Lignans Is Associated with Better Cognitive Performance in Postmenopausal Women
Franco et al.
J. Nutr. 2005;135:1190-1195.
ABSTRACT | FULL TEXT  

The effect of soy protein and soy isoflavones on calcium metabolism in postmenopausal women: a randomized crossover study
Spence et al.
Am. J. Clin. Nutr. 2005;81:916-922.
ABSTRACT | FULL TEXT  

Dietary Soy Containing Phytoestrogens Does Not Activate the Hemostatic System in Postmenopausal Women
Teede et al.
J. Clin. Endocrinol. Metab. 2005;90:1936-1941.
ABSTRACT | FULL TEXT  

Gut Bacterial Metabolism of the Soy Isoflavone Daidzein: Exploring the Relevance to Human Health
Atkinson et al.
Exp. Biol. Med. 2005;230:155-170.
ABSTRACT | FULL TEXT  

Dietary Phytoestrogens to Prevent Cardiovascular Disease: Early Promise Unfulfilled
Sacks
Circulation 2005;111:385-387.
FULL TEXT  

Prospective Study on Usual Dietary Phytoestrogen Intake and Cardiovascular Disease Risk in Western Women
van der Schouw et al.
Circulation 2005;111:465-471.
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  

Isoflavones and Postmenopausal Women
Muanza et al.
JAMA 2004;292:2337-2337.
FULL TEXT  

Isoflavones and Postmenopausal Women
Alekel
JAMA 2004;292:2336-2336.
FULL TEXT  

Isoflavones and Postmenopausal Women
Sirtori
JAMA 2004;292:2336-2337.
FULL TEXT  

Soy Protein: No Cognitive, BMD, or Lipid Benefit
JWatch Women's Health 2004;2004:9-9.
FULL TEXT  

Soy protein isoflavones do not reduce postmenopausal complications
BMJ 2004;329:.
FULL TEXT  

Soy-Protein Supplements Show No Benefit in Postmenopausal Women
Journal Watch Cardiology 2004;2004:4-4.
FULL TEXT  

Isoflavones and Soy Protein in Postmenopausal Women: Disappointing Results
JWatch General 2004;2004:3-3.
FULL TEXT  

Soya supplements do not protect against postmenopausal changes
Gottlieb
BMJ 2004;329:68-68.
FULL TEXT