TY - JOUR
T1 - Nutrikinetic modeling reveals order of genistein phase II metabolites appearance in human plasma
AU - Smit, S.
AU - Szymanska, E.
AU - Kunz, I.
AU - Gomez Roldan, V.
AU - van Tilborg, M.W.E.M.
AU - Weber, P.
AU - Prudence, K.
AU - van der Kloet, F.M.
AU - van Duynhoven, J.P.M.
AU - Smilde, A.K.
AU - de Vos, R.C.H.
AU - Bendik, I.
PY - 2014
Y1 - 2014
N2 - Scope: Genistein from foods or supplements is metabolized by the gut microbiota and the human body, thereby releasingmany different metabolites into systemic circulation. The order of their appearance in plasma and the possible influence of food format are still unknown. This study compared the nutrikinetic profiles of genistein metabolites. Methods and results: In a randomized cross-over trial, 12 healthy young volunteers were administered a single dose of 30mggenistein provided as a genistein tablet, a genistein tablet in low fat milk, and soy milk containing genistein glycosides. A high mass resolution LC-LTQ-Orbitrap FTMS platform detected and quantified in human plasma: free genistein, seven of its phase-II metabolites and 15 gut-derived metabolites. Interestingly, a novel metabolite, genistein-4- glucuronide-7-sulfate (G-4 G7S) was identified. Nutrikinetic analysis using population-based modeling revealed the order of appearance of five genistein phase II metabolites in plasma: (1) genistein-4,7-diglucuronide, (2) genistein-7-sulfate, (3) genistein-4--sulfate-7-glucuronide, (4) genistein-4-glucuronide, and (5) genistein-7-glucuronide, independent of the food matrix. Conclusion: The conjugated genistein metabolites appear in a distinct order in human plasma. The specific early appearance of G-4 ,7-diG suggests a multistep formation process for the mono and hetero genistein conjugates, involving one or two deglucuronidation steps.
AB - Scope: Genistein from foods or supplements is metabolized by the gut microbiota and the human body, thereby releasingmany different metabolites into systemic circulation. The order of their appearance in plasma and the possible influence of food format are still unknown. This study compared the nutrikinetic profiles of genistein metabolites. Methods and results: In a randomized cross-over trial, 12 healthy young volunteers were administered a single dose of 30mggenistein provided as a genistein tablet, a genistein tablet in low fat milk, and soy milk containing genistein glycosides. A high mass resolution LC-LTQ-Orbitrap FTMS platform detected and quantified in human plasma: free genistein, seven of its phase-II metabolites and 15 gut-derived metabolites. Interestingly, a novel metabolite, genistein-4- glucuronide-7-sulfate (G-4 G7S) was identified. Nutrikinetic analysis using population-based modeling revealed the order of appearance of five genistein phase II metabolites in plasma: (1) genistein-4,7-diglucuronide, (2) genistein-7-sulfate, (3) genistein-4--sulfate-7-glucuronide, (4) genistein-4-glucuronide, and (5) genistein-7-glucuronide, independent of the food matrix. Conclusion: The conjugated genistein metabolites appear in a distinct order in human plasma. The specific early appearance of G-4 ,7-diG suggests a multistep formation process for the mono and hetero genistein conjugates, involving one or two deglucuronidation steps.
KW - isoflavone glycosides
KW - soybean isoflavones
KW - healthy-volunteers
KW - bioavailability
KW - pharmacokinetics
KW - disposition
KW - women
KW - daidzein
KW - breast
KW - identification
U2 - 10.1002/mnfr.201400325
DO - 10.1002/mnfr.201400325
M3 - Article
SN - 1613-4125
VL - 58
SP - 2111
EP - 2121
JO - Molecular Nutrition & Food Research
JF - Molecular Nutrition & Food Research
IS - 11
ER -
