Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men.
BACKGROUND
Soy isoflavones are potential cancer chemoprevention treatments.


OBJECTIVE
We conducted safety studies of purified unconjugated genistein, daidzein, and glycitein, and defined pharmacokinetic parameters for their absorption and metabolism.


METHODS
Thirty healthy men ingested a single dose of 1 of 2 isoflavone preparations purified from soy. The delivered doses of genistein (1, 2, 4, 8, or 16 mg/kg body wt) were higher than those previously administered to humans. Formulation A was composed of 90 +/- 5% genistein, 10% daidzein, and 1% glycitein. Formulation B was composed of 43% genistein, 21% daidzein, and 2% glycitein.


RESULTS
We observed no clinically significant behavioral or physical changes after treatment. We observed elevations in lipoprotein lipase and hypophosphatemia that were possibly related to the treatment but that were associated with no clinical toxicity. Considerable quantities of isoflavones were excreted in urine as conjugates. The terminal elimination rate, elimination half-life, area under the curve, maximum plasma concentration, apparent systemic clearance, and volume of distribution were estimated for genistein and daidzein. The mean elimination half-lives with both formulations were 3.2 h for free genistein and 4.2 h for free daidzein. The mean pseudo half-lives were 9.2 h for total genistein and 8.2 h for total daidzein.


CONCLUSIONS
Dietary supplements of purified unconjugated isoflavones administered to humans in single doses exceeding normal dietary intake manyfold resulted in minimal clinical toxicity. Genistein and daidzein (free and total) were rapidly cleared from plasma and excreted in urine.
Busby
Marjorie G
MG
Department of Nutrition, the School of Public Health, the School of Medicine, the University of North Carolina, Chapel Hill 27599-7400, USA.
Jeffcoat
A Robert
AR
Bloedon
LeAnne T
LT
Koch
Matthew A
MA
Black
Tracy
T
Dix
Kelly J
KJ
Heizer
William D
WD
Thomas
Brian F
BF
Hill
Judith M
JM
Crowell
James A
JA
Zeisel
Steven H
SH
D000328:Adult; D016588:Anticarcinogenic Agents / Q000097:blood / Q000493:pharmacokinetics*; D004968:Estrogens, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics; D019833:Genistein / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007529:Isoflavones / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D013025:Glycine max
D016588:Anticarcinogenic Agents; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; C004742:daidzein; C086566:glycitein; D019833:Genistein