Disposition and biotransformation of the estrogenic isoflavone daidzein inrats

Daidzein is an estrogenic isoflavone present in many plants and therefore c onsumed in relatively high doses by humans. Daidzein has a low affinity for the estrogen receptor (3 orders of magnitude lower than estradiol) and has been demonstrated to have estrogenic effects in rodents after administrati on of high doses. We have studied the disposition and biotransformation of daidzein in rats fed a diet low in isoflavone content. Four male and four f emale Fischer 344 rats were orally administered 100 mg/kg daidzein; excrete d urine and feces were collected for 96 h and unchanged daidzein as well as formed metabolites were quantified by HPLC. In urine of male rats, daidzei n, daidzein-glueuronide, and daidzein-sulfate were excreted; in females, on ly unchanged daidzein and daidzein-glucuronide were present. Total urinary excretion of daidzein accounted for < 10% of dose in both males and females . The major pathway of daidzein elimination was excretion of unchanged daid zein with feces. Reductive daidzein-metabolites likely formed by intestinal microflora (equol, O-desmethylangolensin) were excreted with feces in smal l amounts (< 5% of dose). Excretion of daidzein and metabolites with urine and feces was rapid with elimination half-lives of less than 12 h; daidzein concentrations in urine and feces were below the limit of detection 36 h a fter daidzein administration. The results suggest that daidzein is only poo rly absorbed from the gastrointestinal tract in rodents. Absorbed daidzein is rapidly eliminated both unchanged and as conjugates with urine. The inef ficient absorption of daidzein from the gastrointestinal tract and the rapi d excretion may explain the weak estrogenicity of daidzein seen in vivo in rodents when compared to other estrogenic chemicals with comparatively low affinity to the estrogen receptor.