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Alleged benefits experienced by the consumption of soy in Asian countries have been attributed to the isoflavone content of soy products. Amongst other benefits, isoflavones are believed to relieve menopausal symptoms and are therefore often consumed in supplement form in Western countries. These supplements contain relatively high amounts of isoflavones, and the question is if these concentrations still exert beneficial effects or whether negative effects become dominant. Therefore, the investigators will study the effect of intake of one dose of isoflavones, as compared to placebo, for eight weeks on gene-expression in Peripheral Blood Mononuclear Cells (PBMCs) in post-menopausal, equol-producing women.
Primary Objective: to determine the effect of intake of one dose of isoflavones, as compared to placebo, for eight weeks on gene-expression in Peripheral Blood Mononuclear Cells (PBMCs) in post-menopausal, equol-producing women.
Secondary Objectives: to determine the association between isoflavone plasma levels and gene-expression in PBMCs; to determine the variation of isoflavone plasma levels between subjects after intake of isoflavones for four and eight weeks; to explore whether PBMC gene-expression markers identified after 8 weeks isoflavone intervention are already present after 4 weeks intervention; to explore whether the severity of previous menopausal complaints is related to the effect of isoflavones on PBMC gene-expression; and to explore the association between isoflavone levels in plasma and spot urine.
Study design: Double-blind placebo controlled crossover intervention study
Study population: Thirty-six healthy females, 45-70 years, post-menopausal and equol-producing
Intervention: Two intervention periods of eight weeks with a isoflavone supplement or a placebo and a washout period of 8 weeks in between.
Main study parameters/endpoints: The main study parameter is gene-expression in PBMCs measured by micro-arrays.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Isoflavone supplement | Dietary Supplement | The participants will consume 2 times 2 supplements per day, which will lead to a daily dose of 114 mg. (HPLC analysis confirmed an aglycone isoflavone content of 28.41 mg per supplement) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Gene-expression measured by micro-arrays | Gene expression changes will be assessed in PBMCs using whole genome Affymetrix microarrays. The gene expression changes after exposure to the isoflavone supplement will be compared to the changes after exposure to the placebo. | gene-expression after 8 weeks of exposure to the isoflavone supplement |
| Gene-expression measured by micro-arrays | Gene expression changes will be assessed in PBMCs using whole genome Affymetrix microarrays. The gene expression changes after exposure to the isoflavone supplement will be compared to the changes after exposure to the placebo. | after 8 weeks of exposure to the placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Isoflavone levels in plasma and spoturine | levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with High performance liquid chromatography (HPLC). Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with quantitative real-time polymerase chain reaction (QPCR) with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pieter van 't Veer, Professor | Wageningen University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wageningen University | Wageningen | Gelderland | 6703 HD | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23616509 | Derived | van der Velpen V, Geelen A, Schouten EG, Hollman PC, Afman LA, van 't Veer P. Estrogen receptor-mediated effects of isoflavone supplementation were not observed in whole-genome gene expression profiles of peripheral blood mononuclear cells in postmenopausal, equol-producing women. J Nutr. 2013 Jun;143(6):774-80. doi: 10.3945/jn.113.174037. Epub 2013 Apr 24. |
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| after 0 weeks of exposure to the isoflavone supplement |
| Isoflavone levels in plasma and spoturine | levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with HPLC. Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with QPCR with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis. | after 4 weeks of exposure to the isoflavone supplement |
| Isoflavone levels in plasma and spoturine | levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with HPLC. Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with QPCR with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis. | after 8 weeks of exposure to the isoflavone supplement |
| Isoflavone levels in plasma and spoturine | levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with HPLC. Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with QPCR with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis. | after 0 weeks of exposure to the placebo |
| Isoflavone levels in plasma and spoturine | levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with HPLC. Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with QPCR with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis. | after 4 weeks of exposure to the placebo |
| Isoflavone levels in plasma and spoturine | levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with HPLC. Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with QPCR with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis. | after 8 weeks of exposure to the placebo |
| Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) | Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified. | after 0 weeks of exposure to the isoflavone supplement |
| Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) | Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified. | after 4 weeks of exposure to the isoflavone supplement |
| Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) | Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified. | after 0 weeks of exposure to the placebo |
| Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) | Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified. | after 8 weeks of exposure to the isoflavone supplement |
| Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) | Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified. | after 4 weeks of exposure to the placebo |
| Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) | Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified. | after 8 weeks of exposure to the placebo |