Long-term soy isoflavone supplementation and cognition in women

Randomized, placebo-controlled trial in healthy postmenopausal women, including natural and surgical menopause, conducted at the University of Southern California in Los Angeles. In the ISP arm, 175 participants were randomized and 154 were analyzed; in the placebo arm, 175 were randomized and 159 were analyzed.

The active intervention was 25 g/day of isoflavone-rich soy protein (ISP) taken orally as powder or bar form for 2.5 years, providing 91 mg/day aglycone-weight isoflavones (total isoflavone equivalents 154 mg/day; genistein 52 mg, daidzein 36 mg, glycitein 3 mg). The comparator was a milk protein-matched placebo with 0 mg isoflavones.

Long-term ISP did not improve global cognition in healthy postmenopausal women. The primary global cognition outcome at 2.5 years was not significant: mean standardized difference 0.11, 95% CI -0.13 to 0.35, p = 0.36. Visual memory showed a favorable secondary effect for ISP (mean standardized difference 0.33, 95% CI 0.06-0.60), but other cognitive factors and individual tests were not significantly different. Overall, the findings do not support ISP for global cognitive benefit in this population.

Attrition reduced the analyzed sample relative to randomization in both arms, and cognitive benefit was limited to a secondary endpoint. The trial was conducted in healthy postmenopausal women from a single center, which limits generalizability. Follow-up was 2.5 years, and some subgroup findings were not favorable, including analyses suggesting worse global cognition among surgically menopausal women.