Nutrikinetic modeling reveals order of genistein phase II metabolites appearance in human plasma

S. Smit, E. Szymanska, I. Kunz, V. Gomez Roldan, M.W.E.M. van Tilborg, P. Weber, K. Prudence, F.M. van der Kloet, J.P.M. van Duynhoven, A.K. Smilde, R.C.H. de Vos, I. Bendik

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.
Original languageEnglish
Pages (from-to)2111-2121
JournalMolecular Nutrition & Food Research
Volume58
Issue number11
DOIs
Publication statusPublished - 2014

Fingerprint

Genistein
genistein
metabolites
Glucuronides
sulfates
Tablets
Soy Milk
Food
low fat milk
Glycosides
Dietary Supplements
soymilk
Human Body
food matrix
Cross-Over Studies
Sulfates
intestinal microorganisms
Healthy Volunteers
Milk
volunteers

Keywords

  • isoflavone glycosides
  • soybean isoflavones
  • healthy-volunteers
  • bioavailability
  • pharmacokinetics
  • disposition
  • women
  • daidzein
  • breast
  • identification

Cite this

Smit, S., Szymanska, E., Kunz, I., Gomez Roldan, V., van Tilborg, M. W. E. M., Weber, P., ... Bendik, I. (2014). Nutrikinetic modeling reveals order of genistein phase II metabolites appearance in human plasma. Molecular Nutrition & Food Research, 58(11), 2111-2121. https://doi.org/10.1002/mnfr.201400325
Smit, S. ; Szymanska, E. ; Kunz, I. ; Gomez Roldan, V. ; van Tilborg, M.W.E.M. ; Weber, P. ; Prudence, K. ; van der Kloet, F.M. ; van Duynhoven, J.P.M. ; Smilde, A.K. ; de Vos, R.C.H. ; Bendik, I. / Nutrikinetic modeling reveals order of genistein phase II metabolites appearance in human plasma. In: Molecular Nutrition & Food Research. 2014 ; Vol. 58, No. 11. pp. 2111-2121.
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title = "Nutrikinetic modeling reveals order of genistein phase II metabolites appearance in human plasma",
abstract = "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.",
keywords = "isoflavone glycosides, soybean isoflavones, healthy-volunteers, bioavailability, pharmacokinetics, disposition, women, daidzein, breast, identification",
author = "S. Smit and E. Szymanska and I. Kunz and {Gomez Roldan}, V. and {van Tilborg}, M.W.E.M. and P. Weber and K. Prudence and {van der Kloet}, F.M. and {van Duynhoven}, J.P.M. and A.K. Smilde and {de Vos}, R.C.H. and I. Bendik",
year = "2014",
doi = "10.1002/mnfr.201400325",
language = "English",
volume = "58",
pages = "2111--2121",
journal = "Molecular Nutrition & Food Research",
issn = "1613-4125",
publisher = "Wiley-VCH Verlag",
number = "11",

}

Smit, S, Szymanska, E, Kunz, I, Gomez Roldan, V, van Tilborg, MWEM, Weber, P, Prudence, K, van der Kloet, FM, van Duynhoven, JPM, Smilde, AK, de Vos, RCH & Bendik, I 2014, 'Nutrikinetic modeling reveals order of genistein phase II metabolites appearance in human plasma', Molecular Nutrition & Food Research, vol. 58, no. 11, pp. 2111-2121. https://doi.org/10.1002/mnfr.201400325

Nutrikinetic modeling reveals order of genistein phase II metabolites appearance in human plasma. / Smit, S.; Szymanska, E.; Kunz, I.; Gomez Roldan, V.; van Tilborg, M.W.E.M.; Weber, P.; Prudence, K.; van der Kloet, F.M.; van Duynhoven, J.P.M.; Smilde, A.K.; de Vos, R.C.H.; Bendik, I.

In: Molecular Nutrition & Food Research, Vol. 58, No. 11, 2014, p. 2111-2121.

Research output: Contribution to journalArticleAcademicpeer-review

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

VL - 58

SP - 2111

EP - 2121

JO - Molecular Nutrition & Food Research

JF - Molecular Nutrition & Food Research

SN - 1613-4125

IS - 11

ER -