title: Effects of a high daily dose of soy isoflavones on DNA damage, apoptosis, and estrogenic outcomes in healthy postmenopausal women: a phase I clinical trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Unconjugated soy isoflavones appear to be safe and well tolerated in healthy postmenopausal women at doses of 900 mg/day.
authors.affiliation: Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461, USA.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Pop
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Fischer
authors.forename: April D
authors.initials: AD
authors.lastname: Coan
authors.forename: Matt
authors.initials: M
authors.lastname: Gitzinger
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
mesh_terms: D000284:Administration, Oral; D017209:Apoptosis / Q000187:drug effects*; D002214:Capsules; D004249:DNA Damage / Q000187:drug effects*; D019587:Dietary Supplements; D004311:Double-Blind Method; D060754:Equol; D004967:Estrogens / Q000097:blood; D005260:Female; D019833:Genistein / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage* / Q000096:biosynthesis / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects; D008875:Middle Aged; D017698:Postmenopause; D013025:Glycine max
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D002214:Capsules; D004967:Estrogens; D007529:Isoflavones; D060754:Equol; D019833:Genistein