A phase I double-blind clinical trial was conducted to evaluate the effects of a high oral dose of soy isoflavones administered daily for 84 days to healthy postmenopausal women. Principal outcome measures included DNA damage, apoptosis, and changes indicative of estrogenic stimulation.
After eligibility and equol-producer status were determined, stratified randomization was used to assign women to the isoflavone (active) or placebo group. Of the 30 women who completed the study, 18 were in the active group. DNA damage was assessed via COMET and apurinic/apyrimidinic site assays in lymphocytes. Apoptosis was evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and activated caspase-3 assays in lymphocytes. Estrogenic/antiestrogenic effects were assessed using a self-report questionnaire and by assaying for estrogen, follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin in blood.
In treated postmenopausal women, there was no indication that high doses of soy isoflavones caused DNA strand breakage, increased apurinic/apyrimidinic sites, or increased apoptosis in peripheral lymphocytes. There were no significant changes in mean values for estrogenic effects or other laboratory measurements. Very few adverse events occurred, and the only drug-related adverse events were mild or grade 1 in severity.
Unconjugated soy isoflavones appear to be safe and well tolerated in healthy postmenopausal women at doses of 900 mg/day.
In this phase I, double-blinded clinical trial, a high oral dose of soy isoflavones (900 mg/day × 84 days) was well tolerated and did not cause DNA strand breakage, increased apoptosis, or estrogenic effects in treated healthy postmenopausal women.
From the Departments of 1Nutrition, 2Biostatistics, and 3Environmental Sciences and Engineering, and the 4Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Received August 2, 2007; revised and accepted January 8, 2008.
Funding/support: This work was funded by the National Cancer Institute (NCI-N01-CN-75035). Support for this work was also provided by grants from the National Institutes of Health to the University of North Carolina Clinical Nutrition Research Unit (DK56350), the University of North Carolina General Clinical Research Center (RR00046), and the Center for Environmental Health and Susceptibility (ES10126).
Financial disclosure: Dr. Zeisel serves on advisory boards for Dupont, Solae, and Hershey Foods and has received grant support from Mead Johnson and the Egg Nutrition Center. Solae is a producer of soybean derivatives and makes soy isoflavones. A subsidiary of Dupont supplied the tested isoflavone mixture to the National Cancer Institute who then provided it to us. There are no other potential conflicts with the work described. Dr. Fischer is a consultant with Hannaford Bros., Co., and there is no conflict with the work described.
Address correspondence to: Steven Zeisel, MD, PhD, Nutrition Research Institute, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, CB# 7461, Chapel Hill, NC 27599-7461. E-mail: email@example.com