Altered estrogen metabolism and excretion in humans following consumption of indole‐3‐carbinol

Abstract
Research studies have demonstrated a strong association between estrogen metabolism and the incidence of breast cancer, and we have therefore sought pharmacological means of favorably altering both metabolism and subsequent risk. Indole‐3‐carbinol (I3C), obtained from cruciferous vegetables (e.g., cabbage, broccoli, etc.), is a known ihducer of oxidative P‐450 metabolism in animals. We investigated the effects in humans of short‐term oral exposure to this compound (6–7 mg/kg/day over 7 days). We used an in vivo radiometric test, which provided a highly specific and reproducible measure of estradiol 2‐hydroxylation before and after exposure to I3C. In a group of 12 healthy volunteers, the average extent of reaction increased by approximately 50% during this short exposure (p < 0.01), affecting men and women equally. We also measured the urinary excretion of two key estrogen metabolites, 2‐hydroxyestrone (2OHE1) and estriol (E3). We found that the excretion of 2OHE1 relative to that of E3 was significantly increased by I3C, further confirming the ongoing induction of 2‐hydroxylation. These results indicate that I3C predictably alters endogenous estrogen metabolism toward increased catechol estrogen production and may thereby provide a novel “dietary”; means for reducing cancer risk.