Disposition of soy isoflavones in normal human breast tissue.
BACKGROUND
Despite decades of research on the relation between soy and breast cancer, questions regarding the absorption, metabolism, and distribution of isoflavones in breast tissue largely remain unanswered.


OBJECTIVE
We evaluated the potential health effects of isoflavone consumption on normal breast tissue; isoflavone concentrations, metabolites, and biodistribution were investigated and compared with 17beta-estradiol exposure.


METHODS
In this dietary intervention study, healthy women were randomly allocated to a soy milk (n = 11; 16.98-mg genistein and 5.40-mg daidzein aglycone equivalents per dose), soy supplement (n = 10; 5.27-mg genistein and 17.56-mg daidzein aglycone equivalents per dose), or control (n = 10) group. After a run-in period > or = 4 d, 3 doses of soy milk or soy supplements were taken daily for 5 d before an esthetic breast reduction. Blood and breast biopsies were collected during surgery and analyzed with liquid chromatography-tandem mass spectrometry.


RESULTS
After soy administration, genistein and total daidzein concentrations, which were expressed as aglycone equivalents, ranged from 135.1 to 2831 nmol/L and 105.1 to 1397 nmol/L, respectively, in hydrolyzed serum and from 92.33 to 493.8 pmol/g and 22.15 to 770.8 pmol/g, respectively, in hydrolyzed breast tissue. The major metabolites identified in nonhydrolyzed samples were genistein-7-O-glucuronide and daidzein-7-O-glucuronide, with an overall glucuronidation of 98%. Total isoflavones showed a breast adipose/glandular tissue distribution of 40:60, and their mean (+/-SEM) derived 17beta-estradiol equivalents toward estrogen receptor beta were 21 +/- 4-fold and 40 +/- 10-fold higher than the 17beta-estradiol concentrations in adipose (0.283 +/- 0.089 pmol/g, P < 0.001) and glandular (0.246 +/- 0.091 pmol/g, P = 0.001) fractions, respectively.


CONCLUSIONS
After intake of soy milk and soy supplements, isoflavones reach exposure levels in breast tissue at which potential health effects may occur.
Bolca
Selin
S
Laboratory of Microbial Ecology and Technology, Faculty of Bioscience Engineering and the Laboratory of Experimental Cancer Research, Department of Experimental Cancer Research, Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium.
Urpi-Sarda
Mireia
M
Blondeel
Phillip
P
Roche
Nathalie
N
Vanhaecke
Lynn
L
Possemiers
Sam
S
Al-Maharik
Nawaf
N
Botting
Nigel
N
De Keukeleire
Denis
D
Bracke
Marc
M
Heyerick
Arne
A
Manach
Claudine
C
Depypere
Herman
H
D000273:Adipose Tissue / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001940:Breast / Q000378:metabolism*; D002853:Chromatography, Liquid; D019587:Dietary Supplements; D004958:Estradiol / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D042361:Mammary Glands, Human / Q000378:metabolism; D008875:Middle Aged; D048789:Phytoestrogens / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000493:pharmacokinetics*; D012016:Reference Values; D045730:Soy Foods; D013025:Glycine max / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution / Q000187:drug effects; D055815:Young Adult
D047629:Estrogen Receptor beta; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; D004958:Estradiol; C004742:daidzein; D019833:Genistein