Scientific Publications by FDA Staff

Neurotoxicol Teratol 2014 Jan-Feb;41:80-8

The effects of dietary treatment with S-equol on learning and memory processes in middle-aged ovariectomized rats.

Neese SL, Pisani SL, Doerge DR, Helferich WG, Sepehr E, Chittiboyina AG, Rotte SC, Smillie TJ, Khan IA, Korol DL, Schantz SL

The use of over-the-counter botanical estrogens containing isolated soy isoflavones, including genistein and daidzein, has become a popular alternative to traditional hormone therapies. Menopausal women use these products as an aide in healthy aging, including for the maintenance of cognitive function. The safety and efficacy of many of these commercial preparations remains unknown. Previous research in our lab found that treatment of ovariectomized (OVX) female Long-Evans rats with genistein impaired working memory in an operant delayed spatial alternation (DSA) task and response learning in a plus-maze, but enhanced place learning assessed in the plus-maze. The present study further examined the effects of isolated isoflavones on working memory and place learning by treating middle-aged (12-13month old) OVX female Long-Evans rats with S-equol, the exclusive enantiomer produced by metabolism of daidzein in the mammalian gut. S-equol binds selectively to ERbeta with an affinity similar to that of genistein but has low transcriptional potency. For DSA testing, S-equol at 1.94, 0.97mg, or 0mg (sucrose control) was orally administered to animals daily, 30minutes before behavioral testing, and again both 4 and 8hours after the first treatment. Rats were tested on the DSA task following the first, morning dose. For place learning, rats received 0.97mgS-equol every 4hours during the light portion of the cycle beginning 48hours prior to behavioral testing (total exposure 8.7mgS-equol). S-equol treatment was largely without effect on the DSA and place learning tasks. This is the first study to test the behavioral effects of isolated S-equol in OVX rodents, and shows that, unlike genistein or estradiol, repeated daily treatment with this isoflavone metabolite does not alter learning and memory processes in middle-aged OVX rats.