**1. Introduction**

The significance of virgin olive oil (VOO), hinged to its many virtues in both gastronomy and health, is nowadays undeniable. Their protective effects are attributed to its high content of monounsaturated fatty acids and to the presence of some minor components, which add up to 2% of the weight. Among its several minor constituents, polar phenolic compounds, usually characterized as polyphenols, have become the subject of intensive research because of their biological activities, their influence on the organoleptic properties of VOO and their contribution to its oxidative stability (Bendini et al., 2007).

The phenolic fraction of VOO consists of a heterogeneous mixture of compounds belonging to several families with varying chemical structures. A brief description of the main classes of phenolic compounds contained in VOO is given below:


The qualitative and quantitative composition of VOO hydrophilic phenols is strongly affected by the agronomic and technological conditions of production (Servili et al., 2004). Among agronomic parameters, the cultivar, the fruit ripening degree, the agronomic

Metabolism and Bioavailability of Olive Oil Polyphenols 335

ingested amount of polyphenols is able to exert its beneficial effects in the target tissues. It is important to realize that the most abundant phenolic compounds in our diet are not necessarily those that have the best bioavailability profile, either because they have a lower intrinsic activity or because they are poorly absorbed from the intestine, highly metabolized, or rapidly eliminated. In addition, the metabolites that are found in blood and target organs, resulting from digestive or hepatic activity, may differ from the native compounds in terms

Although the information concerning the bioavailability of most olive oil polyphenols is limited, intensive research has been carried out in the past decade. This fact is reflected in the number of reviews published since 2002 (Corona et al., 2009; Covas et al., 2009; de la Torre, 2008; Fitó et al., 2007; Tuck & Hayball, 2002; Visioli et al., 2002; Vissers et al., 2004). To address the bioavailability of olive oil phenolic compounds, we have reviewed *in vitro* and *in vivo (*both animal and human) studies on the absorption, transport, metabolism and

Direct evidence on bioavailability of olive oil phenolic compounds has been obtained by measuring the concentration of the polyphenols and their metabolites in biological fluids, mostly plasma and urine, after ingestion of pure compounds or of olive oil, either pure or enriched with the phenolics under study. The majority of research regarding the bioavailability of olive oil polyphenols has been focused on three major phenolics: Hyty, Ty

After ingestion, olive oil polyphenols can be partially modified in the acidic environment of the stomach. The effect of such environment on aglycone secoiridoids has been examined *in vitro* by incubating the compounds at 37 ºC in simulated gastric pH conditions and during normal physiological time frames (Corona et al., 2006; Pinto et al., 2011). Although hydrolysis takes place releasing free phenolic alcohols, a significant amount remains intact and thus, enters the small intestine unmodified. Ol Agl and its dialdehydic form, however, are likely not absorbed as such in the small intestine; the major metabolites detected using the perfused rat intestine model were the glucuronide conjugates of the reduced form of

Manna et al. (2000) carried out studies on the transport kinetics of radiolabeled Hyty using differentiated Caco-2 cells. The only metabolite found in the culture medium was the methylated derivative (i.e. homovanillic alcohol - HVAlc). They also demonstrated that Hyty was transported across the membrane of the human enterocytes by a bidirectional passive diffusion mechanism. Caco-2/TC7 cell monolayers have been used to study the metabolism of other olive oil polyphenols, such as Ty, *p*-coumaric acid, pinoresinol, luteolin (Soler et al., 2010) and Hyty acetate (Mateos et al., 2011). Results showed that the methylated conjugates are the main metabolites and that the acetylation of Hyty significantly increases its transport across the small intestinal epithelial cell barrier, enhancing the delivery of Hyty

To study the potential hepatic metabolism of olive oil phenols, human hepatoma HepG2 cells were incubated for 2 and 18 h with Ty, Hyty and Hyty acetate (Mateos et al., 2005). Extensive uptake and metabolism of Hyty and Hyty acetate were observed, with scarce metabolism of Ty. Hyty acetate was converted into free Hyty and then metabolized;

of biological activity (Manach et al., 2004).

excretion of olive oil phenolic compounds.

and Ol, as can be seen in **Tables 1** and **2**.

both compounds (Pinto et al., 2011).

to the enterocytes.

**2.1 Absorption and disposition** 

techniques used and the pedoclimatic conditions are the aspects more extensively studied (Tovar et al., 2001; Uceda et al., 1999). Moreover, by modulating technology, it is possible to some extent to optimize the transfer of some polar minor constituents into the oil or reduce their level (Boskou, 2009). The influence of variety, extraction system, ripening degree and storage in the polyphenolic content of a VOO has been extensively discussed in the literature (Boskou, 2009; Uceda et al., 1999).

Wide ranges of total polar phenols concentration have been reported in olive oils (50-1000 mg/kg), although the most usual value is found between 100-350 mg/kg (Boskou et al., 2006). In general, the most abundant phenolic compounds in VOO are aglycones deriving from secoiridoids. Trying to establish levels of individual phenols, Servili & Montedoro (2002) calculated average values of 7 phenolic compounds from a considerable number of samples of industrial olive oils. They concluded that Hyty and Ty were found only in trace amounts (less than 10 mg/kg oil) and the most abundant phenols were decarboxylated Ol Agl (63-840 mg/kg), Ol Agl (85–310 mg/kg), and decarboxylated Lig Agl (15-33 mg/kg). Brenes et al. (2002) published values ranging from 3-67 mg/kg for 1-acetoxypinoresinol, and from 19-41 mg/kg for pinoresinol in 5 Spanish olive oils, data that can be completed with the researches carried out by Romero et al. (2002) and Tovar et al. (2001). Levels of luteolin have been found to be around 10 mg/kg in some Spanish olive oils (Brenes et al., 1999) or ranging between 0.2-7 mg/kg for Greek oils (Murkovic et al., 2004). Carrasco-Pancorbo et al. (2006) developed a method to quantify 14 individual phenols belonging to different families in 7 Spanish extra-virgin olive oils (EVOOs). They also quantified them, finding the following contents (mg/kg): simple phenols: 6.8-11.5; complex phenols: 70.5-799.5; lignans: 0.81-20.6; and flavonoids: 1.4-8.6.

Intake of olive oil in the Mediterranean countries is estimated to be 30–50 g/day, based on the per capita olive oil consumption of 10–20 kg/year in Greece, Italy and Spain (Boskou, 2000; Food and Agricultural Organization, 2000). A daily consumption of 50 g olive oil with a concentration of 180 mg/kg of phenols would result in an estimated intake of about 9 mg of olive oil phenols per day (de la Torre, 2008; Vissers et al., 2004), of which at least 1 mg is derived from free Hyty and Ty, and 8 mg are related to their elenolic esters and also to Ol Agl and Lig Agl (de la Torre, 2008). Some other estimations have been made. For the Greek population (Dilis & Trichopolou, 2009), the daily per-capita intake is about 17 mg. Vissers et al. (2004) estimated that about 1 mg of the phenol intake per day (6 mmol) is derived from Hyty and Ty, about 8 mg (23 mmol) from the aglycones, and so the total phenol intake would be about 29 mmol.
