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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).

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