Dietary polyphenols, including quercetin, have been associated with beneficial health effects. Epidemiological studies show an association of dietary quercetin intake with a reduction in cardiovascular disease risk.
Whole genome microarray and real time PCR analysis of lung and transcriptome and proteome analysis of the colon of rats chronically fed dietary quercetin showed that fatty acid (FA) catabolism pathways are up-regulated in both organs, by the long-term quercetin interventions. Importantly, plasma free fatty acid (FFA) levels were decreased in rats fed the quercetin diet, confirming that quercetin affects FA catabolism. FFA levels are an important risk factor in the development of insulin resistance and in the cardiovascular complications associated with overweight and obesity. The effect of quercetin on lipid catabolism may well explain the beneficial effects observed in epidemiological studies.
We hypothesize that changes in fatty acid metabolism underlie the quercetin- and flavonoid- mediated beneficial health effects on cardiovascular disease risk. Liver is a major effector organ of lipid metabolism. Liver also is the prime metabolic tissue, thus potentially adverse effects of high doses as used in supplements could lead to toxic effects in this tissue. In addition, human intervention studies with antioxidant supplements showed an increased mortality risk.
- Structure-activity characteristics for flavonoids will be performed to identify the most active flavonoid congener(s) using an in vitro assay for relevant effects found previously (2010) This assay is focused on effects on energy metabolism pathways, including FA catabolism, may be mediated by PPAR-alpha, but other receptors may also play a role.
- A mouse dietary intervention study with selected active flavonoids will be performed to assess bioavailability and the in vivo effects. The most active flavonoids that emerged from this in vitro studies will be used and the analysis will focus on biomarkers for cardiovascular disease, liver damage and liver and PBMC gene expression.
- A human intervention study will be performed to check if similar changes in plasma FFAs and cardiovascular biomarkers and PBMC gene expression are observed in human volunteers taking a flavonoid supplement. Correlation with plasma flavonoid levels will be determined.
- A risk-benefit assessment will be made for high level flavonoid intake using the outcomes obtained and evaluating potential adverse effects of high level flavonoid supplementation against the possible beneficial effects on cardiovascular disease risks defined in the present project.
The market for healthy foods is growing rapidly. Foods with increased concentrations of health promoting bioactives have promising perspectives. Yet, tools for a balanced evaluation of health benefits and potential adverse effects are not sufficiently developed. The present project will add to the development of these tools.
The results will be published in peer-reviewed papers and will be presented at scientific conferences.
Interference of flavonoids with enzymatic assays for the determination of free fatty acid and triglyceride levelsAnalytical and Bioanalytical Chemistry 402 (2012)3. - ISSN 1618-2642 - p. 1389 - 1392.
Quercetin decreases high-fat diet induced body weight gain and accumulation of hepatic and circulating lipids in miceGenes & Nutrition 9 (2014). - ISSN 1555-8932 - 8 p.
Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in miceIn: Annals of Nutrition & Metabolism : Abstracts of the 20th International Congress of Nutrition. - Munich : Karger - ISBN 9783318025163 - p. 149 - 149.
Quercetin induces hepatic lipid omega-oxidation and lowers serum lipid levels in micePLoS ONE 8 (2013)1. - ISSN 1932-6203 - 10 p.