Projects per year
Background: Risk assessment can potentially be improved by closely linked experiments in the disciplines of epidemiology and toxicology. This was explored for isoflavones in a case study. For isoflavones potential beneficial health effects have been suggested, but discussions on their safety are ongoing as well.
Aims and methods: Effects of isoflavone supplements on gene expression were studied in white blood cells (PBMCs) and adipose tissue, among postmenopausal women in two human intervention studies. To advance risk assessment, the dose response relation between intake and blood levels was studied with a log-linear regression model as well as the comparability of the human gene expression profiles with results from a rat experiment using multivariate analysis.
Results: In both PBMCs and adipose tissue, changes in gene expression profiles pointed at effects of isoflavones on energy metabolism, inflammation and cell cycle; these effects were modified by supplement composition and equol-producing phenotype. Hypothesized estrogen-responsive effects were not observed. For the intake range of 0-100mg/day, the plasma concentrations of daidzein, equol, genistein and total isoflavones were quantified, interindividual variation. Expression of estrogen-responsive gene profiles and other biological pathways could be quantitatively compared between PBMCs and adipose tissue, as well as between humans and rats. en nog iets
Conclusion: Effects of isoflavone supplementation on gene expression in PBMCs and adipose tissue of postmenopausal women suggest mainly beneficial effects of a dose of ~100mg/day. The absence of a clear estrogen-like response suggested a limited role of the estrogen receptor in isoflavone induced gene expression in postmenopausal women. The trials and quantitative models provide important tools[AG1] that enable further exploration of intertissue and interspecies comparability and advancing the use of transcriptomics in assessing risks and benefits.
Modelling data from human and animal studies provide important possibilities for further exploration of intertissue and interspecies similarities and for the use of transcriptomics in improving risk assessment.
|Qualification||Doctor of Philosophy|
|Award date||20 Jun 2014|
|Place of Publication||Wageningen|
|Publication status||Published - 2014|
- food supplements
- risk assessment
- gene expression
- exposure assessment
Improvement of risk assessment by integrating toxicological and epidemiological approaches: the case of isoflavones.
16/11/09 → 20/06/14