Advances in the knowledge of olive oil phenolic compounds. From biotransformations after their intake to their metabolic fate for exerting biological activities

Abstract

ABSTRACT Olive oil, the main source of fat in the Mediterranean diet, possesses an exclusive family of phenolic compounds (OOPCs) located in the unsaponifiable fraction, with hydroxytyrosol (HT) being the most bioactive molecule. Previous in-vitro, in-vivo and epidemiological studies revealed that OOPCs, especially HT, possess pharmacological properties. For these reasons, the European Food Safety Authority (EFSA) made a health claim stating that the properties of OOPCs countered the development of cardiovascular diseases. Since then, an ever-expanding range of products based on OOPCs has come onto the market, but there is little information about the dose effects and the form in which these compounds become more bioavailable. In this Doctoral Thesis, my aim was to deepen the knowledge of HT metabolism and biotransformation during gastrointestinal tract transit and to study the impact of the dose and the chemical structure for its bioavailability. Also, I aim to study the contribution of plasmatic metabolites to the development of cardiovascular diseases and to highlight the molecular mechanism of action by studying the aorta and heart proteome. In addition, my goal was to study the biotransformations that occur in the digestive tract as a consequence of microbial metabolisms and the potential activity against colon cancer. My results show that the administration of different precursors of HT has a broad impact on its bioavailability. The administration of the most complex HT precursors (secoiridoids, and especially oleuropein) increases the bioavailability of HT and also, its plasmatic metabolites. Also, it seems that the phase-II metabolites of HT, with HT sulfate being the most ubiquitous metabolite in plasma, could display biological activity. The colonic metabolites of HT may be of interest for future studies to evaluate its preventive bioactivity against colon cancer. In conclusion, both the native molecule and its derived metabolites formed during digestion (microbial and enzymatic) help to maintain health status.