Long-term soy isoflavone supplementation and cognition in women A randomized, controlled trial

Departments of Health Research and Policy (Epidemiology) and Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Neurology (Impact Factor: 8.29). 06/2012; 78(23):1841-8. DOI: 10.1212/WNL.0b013e318258f822
Source: PubMed


To determine the cognitive effects of long-term dietary soy isoflavones in a daily dose comparable to that of traditional Asian diets.
In the double-blind Women's Isoflavone Soy Health trial, healthy postmenopausal women were randomly allocated to receive daily 25 g of isoflavone-rich soy protein (91 mg of aglycone weight of isoflavones: 52 mg of genistein, 36 mg of daidzein, and 3 mg glycitein) or milk protein-matched placebo. The primary cognitive endpoint compared between groups at 2.5 years was change from baseline on global cognition, a composite of the weighted sum of 14 neuropsychological test score changes. Secondary outcomes compared changes in cognitive factors and individual tests.
A total of 350 healthy postmenopausal women aged 45-92 years enrolled in this trial; 313 women with baseline and endpoint cognitive test data were included in intention-to-treat analyses. Adherence in both groups was nearly 90%. There was no significant between-group difference on change from baseline in global cognition (mean standardized improvement of 0.42 in the isoflavone group and 0.31 in the placebo group; mean standardized difference 0.11, 95% confidence interval [CI] -0.13 to 0.35). Secondary analyses indicated greater improvement on a visual memory factor in the isoflavone group (mean standardized difference 0.33, 95% CI 0.06-0.60) but no significant between-group differences on 3 other cognitive factors or individual test scores, and no significant difference within a subgroup of younger postmenopausal women.
For healthy postmenopausal women, long-term dietary soy isoflavone supplementation in a dose comparable to that of traditional Asian diets has no effect on global cognition but may improve visual memory. Classification of evidence: This study provides Class I evidence that long-term dietary supplementation with isoflavone-rich soy protein does not improve global cognition of healthy postmenopausal women.

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Available from: Wendy Mack, Feb 24, 2014
    • "As noted previously, the few intervention studies conducted so far enrolled primarily younger, cognitively healthy, postmenopausal women. A large randomized, controlled trial enrolling postmenopausal women age 45 to 92 revealed a decline on general intelligence with soy treatment, but a beneficial effect for visual memory [18]. The conflicting results may explain why findings from small trials are highly mixed [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]. "
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    ABSTRACT: Background: In a previous trial, treatment with soy isoflavones was associated with improved nonverbal memory, construction abilities, verbal fluency, and speeded dexterity compared to treatment with placebo in cognitively healthy older adults. Objective: The current trial aimed to examine the potential cognitive benefits of soy isoflavones in patients with Alzheimer's disease. Methods: Sixty-five men and women over the age of 60 were treated with 100 mg/day soy isoflavones, or matching placebo capsules for six months. APOE genotype was determined for all participants. Cognitive outcomes and plasma isoflavone levels were measured at baseline, and at two additional time points: three and six months after baseline. Results: Of the sixty-five participants enrolled, thirty-four (52.3% ) were women, and 31 (47.7% ) were APOEɛ4 positive. Average age was 76.3 (SD = 7.2) years. Fifty-nine (90.8% ) subjects completed all study visits. Plasma isoflavone levels increased in subjects treated with soy isoflavones compared to baseline and to placebo, although intersubject variability in plasma levels was large. No significant differences in treatment effects for cognition emerged between treatment groups or genders. Exploratory analyses of associations between changes in cognition and plasma isoflavone levels revealed an association between equol levels, and speeded dexterity and verbal fluency. Conclusions: Six months of 100 mg/day treatment with soy isoflavones did not benefit cognition in older men and women with Alzheimer's disease. However, our results suggest the need to examine the role of isoflavone metabolism, i.e., the ability to effectively metabolize soy isoflavones by converting daidzen to equol when attempting to fully clarify the cognitive effects of isoflavones.
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    • "Few RCTs have been performed with soy supplementation, with controversial results. A long-term supplementation of soy in women had no effect on global cognition but improved visual memory after thirty months (Henderson et al., 2012), while in men, treated for twelve weeks, only spatial working memory improved compared to the placebo group (Thorp et al., 2009). A previous study in postmenopausal women who received soy protein for twelve months had no benefit in cognitive performance (Kreijkamp-Kaspers et al., 2004). "
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