Effect of Soy Protein Containing Isoflavones on Cognitive Function, Bone Mineral Density, and Plasma Lipids in Postmenopausal Women: A Randomized, Controlled Trial

Abstract

Declining estrogen levels at menopause are accompanied by deteriorating cognitive function. Postmenopausal estrogen therapy might counteract this and other perimenopausal changes such as increasing plasma lipid levels and decreasing bone mineral density (BMD). Even short-term estrogen therapy, however, may cause recurrent vaginal bleeding, and long-term replacement has been related to increased risks of breast cancer, cardiovascular disease, and stroke. Phytoestrogens such as isoflavones and lignans are estrogen-like compounds found in plant foods that activate estrogen receptors and, in the postmenopausal state, may act as agonists. The investigators sought to determine the effects of supplemental soy protein, which contains the isoflavones genistein and daidzein, on cognitive function, BMD, and plasma lipids. A double-blind, randomized, placebo-controlled trial enrolled 202 healthy postmenopausal women 60 to 75 years of age, who were randomized to receive 25.6 g of soy protein containing 99 mg of isoflavones in powder form or a placebo each day for 12 months. In addition to the Mini-Mental State Examination, participants were evaluated by short- and long-term tests of verbal and visual memory and measures of naming and verbal fluency. BMD was estimated at the hip and lumbar spine by dual-energy x-ray absorptiometry. Baseline cognitive performance was similar in the study and control groups. Women given soy did slightly better on most tests of memory, but the differences were not statistically significant or clinically meaningful. Tests of verbal skills, concentration, and visual attention showed no significant between-group differences. Comparable results were obtained after excluding women who were depressed. The findings were not influenced by years since menopause, body mass index, smoking status, or history of estrogen therapy. BMD declined in both groups after 12 months. Plasma levels of low-density lipoprotein cholesterol and total cholesterol did not change in the soy group and decreased slightly in the placebo group. The findings of this randomized trial fail to support the possibility that isoflavones in soy protein have beneficial effects on cognitive function, BMD, or plasma lipids in healthy postmenopausal women aged 60 and older.