Isoflavones and cognition - Women's Health Update

Townsend Letter for Doctors and Patients,  Oct, 2003  by Tori Hudson

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Healthy postmenopausal women, aged 55 to 74 who had normal cognition, participated in a 6 month, double-blind, randomized, placebo-controlled clinical trial, called the Soy and Postmenopausal Health in Aging Study (SOPHIA). They were not on estrogen replacement therapy and were at least 2 years postmenopausal. Women were randomized into two groups, a placebo group and one who took 110 mg soy isoflavones in pills. Cognitive function tests were administered at baseline and follow-up using a standard questionnaire, the Beck Depression Inventory, the Mini-mental Status Examination (a screening test for dementia), Trails A and Trails B from the Halstead-Reitan Neuropsychological Test Battery (an instrument used to demonstrate differences among older individuals in cognitive function), Category Fluency (a test of verbal memory), and a memory and recall test from the Wechsler memory scale.

In this clinical trial, isoflavone supplementation significantly improved performance on category fluency and showed a nonsignificant pattern of improvement on other tests of verbal memory, visuomotor tracking and attention. Isoflavone supplementation in the older women in the treatment group was associated with improved performance in cognitive function scores over time.

Commentary: The results of this study are consistent with laboratory studies suggesting a beneficial effect of isoflavones on cognitive function in estrogen deficient states (1) and the results of a small clinical trial in college students. In this study, both men and women who had improvements in short term memory and mental flexibility while eating a high soy diet of 100 mg total isoflavones per day. (1,2) In addition, women in the high soy group also showed improvement in a letter fluency test. A study on brain aging and tofu consumption did not fair so well. Poor cognitive test performance, enlargement of the ventricles, and low brain weight in men were each associated with consumption of tofu 2 or more times per week during midlife. (3)

It is considered biologically plausible that isoflavones have a beneficial effect on cognitive function. In the brain, isoflavones seem to bind preferentially to estrogen receptor beta receptors and the area of the brain thought to mediate verbal memory is rich in ER beta receptors. It has been shown that estrogen increases glucose uptake in several regions of the brain, and increases blood flow to the hippocampus region.

Recent meta-analysis of Alzheimer's disease and hormone replacement therapy showed a 34% decreased risk of Alzheimer's in hormone users. (4) However, even more recently, an ancillary study of the Women's Health Initiative, called the Women's Health Initiative Memory Study (WHIMS) revealed that women on Premarin and Provera for 4 or more years, overall had twice the risk of dementia than women in the placebo group (5) and had a clear detrimental effect in cognitive function. (6)

The results of the two WHIMS studies demonstrate that estrogen plus progestin therapy, at least conjugated equine estrogens and medroxyprogesterone acetate, increases older women's risk for dementia and does not protect against mild cognitive impairment. Speculation leads us to think that the HRT regimen may be related to silent brain infarcts, increase in pro-inflammatory markers, and clot-related events. While we know that soy has favorable effects on lipids, we know less as to the effects of soy on clotting factors and inflammatory markers. Given that soy is related to a lower risk of cardiovascular disease, it looks promising that these other markers may also be favorably affected by soy, which bodes well for the brain. However, we have a long way to go before we understand the effects of both soy and estrogen on the brain. Perhaps the answer will lie in a better understanding of the estrogen receptors and a better understanding of different kinds of estrogens and their effect on these receptors.

Kritz-Silverstein D, Von Muhlen D, Barrett-Connor E, Bressel M. Tsoflavones and cognitive function in older women: the SOY and postmenopausal health in aging study (SOPHIA). Menopause 2003;19(3):196-02

Tori Hudson, ND

Professor, National College of Naturopathic Medicine and Bastyr University

Medical Director, A Woman's Time

Author, Women's Encyclopedia of Natural Medicine

2067 N.W. Lovejoy * Portland, Oregon 97209 USA

503-222-2322 * womanstime@aol.com

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