Soy isoflavone (IF) supplementation appears safe after a two‐year randomized controlled trial (RCT)

Abstract

Although RCTs quantifying a benefit for menopausal soy IF supplementation abound, few studies have considered the safety of long‐term soy IF intake, particularly when exposure levels are in the form of a tablet, as opposed to food. To evaluate the effect of soy IF on bone loss, 403 early postmenopausal women (54.0±4.0 y) were enrolled in a multi‐site, 2‐year, double‐blind RCT with 1/3 on placebo, 1/3 on 80 mg/d IF and 1/3 on 120 mg/d IF. Baseline characteristics were similar in all groups. The study design focused on safety as a secondary outcome measure and included serum electrolytes, lipids, liver and renal functions, complete blood counts, reproductive and thyroid hormones and cancer (CA) screening. In the supplement groups versus placebo, there was a decrease in free thyroxine (T4) (p=0.024) and an increase in blood urea nitrogen (BUN) (p=0.048), but not thyroid stimulating hormone (p=0.264) or creatinine (p=0.145) after 2 years. Absolute changes in free T4 and BUN were neither outside the normal range nor clinically significant. Major adverse events included one subject with endometrial CA and one with breast CA, which were fewer than predicted in this study population. Soy IF supplementation up to 120 mg/d has no measurable deleterious effect over a 2‐year interval. Supported by Initiative for Future Agriculture and Food Systems Grant 2001‐52102‐11255 USDA CSREES.