# Cellular Antioxidant Effects and Bioavailability of Food Supplements Rich in Hydroxyrosol
## 1 Introduction  
Many consumers associate the fruit of the olive tree (_Olea europaea_ L.) mainly with the resulting oil, the precious olive oil that is considered particularly healthy compared to other oils. The raw olive fruit contains several types of phenols, the contents of which vary with the olive cultivar, mainly tyrosol and its derivatives, phenolic acids, and flavonoids [1]. However, many of these substances that the olive has to offer from a health perspective are water-soluble, and thus remain largely in the residue of the olive pressing and the oil contains only a small part. This is the case of hydroxytrosol, a polar phenol slightly soluble in fats, which can be found in olives as a simple phenol, or either esterified with elenolic acid to form oleuropein aglycone, and which is naturally present in significantly higher concentrations in the olive fruit's aqueous fraction.  
The vegetation water, resulting from the pressing of the olive fruits duringthe production of the olive oil, is rich in bioactive compounds, particularly polar phenols, and typically contains 98% of the total phenols of the olive fruit [2].  
The positive health effects of olive polyphenols are already known; in particular, hydroxytrosol has potential antioxidant, anti-inflammatory, and health benefits mainly related with cardiovascular diseases [3; 4; 5; 6].  
Bioavailability and pharmacokinetic analyses, which were mainly reported with pure hydroxytrosol and with olive oil, suggest that hydroxytrosol can be rapidly absorbedfrom blood and distributed in the human body [7], metabolized, and quickly eliminated in urine mainly as glucuronide and sulfate [8]. Currently, hydroxytrosol from different sources is available on the market. Its absorption and subsequent urine excretion may be dependent on the vehicle of administration [9]. Thus, the bioavailability of hydroxytrosol and its precursors (oleuropein and tyrosol) from those specific sources would be a prerequisite for its health effects in humans.  
The present study addresses the bioactivity of hydroxytrosol-rich extracts, obtained from the vegetation water resulting from olive oil production. Herein, hydroxytrosol is present as both a simple phenol and as oleuropein aglycone.  
For the study, olive-derived concentrates combined with 6% lemon juice or 70% grape juice and marketed as liquid supplements were characterized. Bioactivities, mainly related to the antioxidant potential, were evaluated in cultured cells by means of the antioxidant capacity (cellular antioxidant activity assay, superoxide dismutase and catalase activities), the protection against lpixolation (inhibition of F2-isoprostanes formation) and glycation (inhibition of AGEs formation). In addition, preliminary data on the bioavailability and urinary recovery of free hydroxytrosol through acute administration of the food supplements are presented from an open-label cross-over study with four volunteers.  
Despite the difference in the composition of both formulations, the main phytochemicalal in the ones that were investigated was hydroxytrosol, present in both olive fruit and to a lesser extent in grapes. The treatment of the cells with the supplements gave positive results, although these were slightly different in magnitude, through antioxidant actions. The high bioactivity observed suggests a possible application in the maintenance of the cellular redox state and for related health benefits.