Biological Activities of Phenolic Compounds Present in Virgin Olive Oil

By Sara Cicerale, Lisa Lucas and Russell Keast. School of Exercise and Nutrition Sciences, Deakin University,Exit Site Melbourne, Australia. February 2010

Abstract: The Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular disease, neurodegenerative diseases and certain types of cancer. The apparent health benefits have been partially ascribed to the dietary consumption of virgin olive oil by Mediterranean populations. Much research has focused on the biologically active phenolic compounds naturally present in virgin olive oils to aid in explaining reduced mortality and morbidity experienced by people consuming a traditional Mediterranean diet. Studies (human, animal, in vivo and in vitro) have demonstrated that olive oil phenolic compounds have positive effects on certain physiological parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet and cellular function, antimicrobial activity and bone health. This paper summarizes current knowledge on the bioavailability and biological activities of olive oil phenolic compounds.


ADDL, beta-amyloid oligomers; CHD, coronary heart disease; COX-1, cyclooxygenase-1; COX-2, cyclooxygenase-2; CRP, C-reactive protein; CVD, cardiovascular disease; DNA, deoxyribonucleic acid; FVII, factor VII; g, gram; GSSG, glutathionedissulfide; GSH, reduced glutathione; GSH-Px, glutathione peroxidise; HDL-C, high density lipoprotein cholesterol; IL-6, interleukin-6; LDL, low density lipoprotein; LDL-C, low density lipoprotein cholesterol; LPO, lipid peroxidation; LTB4, leukotriene B4; MUFA, monounsaturated fatty acid; µM, micromolar; µg, microgram; oxLDL, low density lipoprotein oxidation; 8-oxo-dg, 8-oxo-2'-deoxyguanosine; PAI-1, plasminogen activator inhibitor-1; ROS, reactive oxygen species; sICAM-1, soluble intercellular molecules; sVCAM-1, soluble vascular adhesion molecules; Tau, microtubule-associated protein; TC, total cholesterol; TG, triglyceride; TXB2, thromboxane B2

1. Introduction

A lower prevalence of non-communicable diseases such as cardiovascular disease and certain types of cancers have been demonstrated in countries residing in the Mediterranean region in comparison to other parts of the world [1–9]. This lowered incidence has been partially attributed to the regular intake of virgin olive oil as part of a traditional Mediterranean diet [3,5,9,10–17]. Dietary consumption of virgin olive oil in a Mediterranean diet typically ranges between 25–50 mL per day [18]. Virgin olive oil is produced from the first and second pressings of the olive fruit by the cold pressing method (where no chemicals and only a small amount of heat are applied) and is composed of a glycerol fraction (making up 90–99% of the olive fruit) and a non-glycerol or unsaponifiable fraction (making up 0.4–5% of the olive fruit) which contains phenolic compounds [19]. Historically, the beneficial health effects of virgin olive oil intake were attributed to the glycerol fraction with its high concentration of monounsaturated fatty acids (MUFAs) (particularly oleic acid) [19]. However, several seed oils (including sunflower, soybean, and rapeseed) containing high quantities of MUFAs are ineffective in beneficially altering chronic disease risk factors [20,21]. Therefore, a substantial number of investigations examining the biological actions of olive oil phenolic compounds in the unsaponifiable fraction have been conducted. In this paper, the term virgin olive oil will be used to describe both extra virgin and virgin olive oil.

Studies conducted thus far (including human, animal, in vivo and in vitro) have demonstrated that olive oil phenolic compounds have positive effects on various physiological biomarkers, implicating phenolic compounds as partially responsible for health benefits associated with the Mediterranean diet [3,5,22–27]. Furthermore, olive oil phenolic compounds have been shown to be highly bioavailable, reinforcing their potential health promoting properties [28–33]. The phenolic fraction of virgin olive oil is heterogeneous, with at least 36 structurally distinct phenolic compounds identified. Variation in the phenolic concentration exists between differing virgin olive oils due to numerous factors including: variety of the olive fruit [34–42], region in which the olive fruit is grown [37], agricultural techniques used to cultivate the olive fruit [34,43,44], maturity of the olive fruit at harvest [35,39,44–48], and olive oil extraction, processing, storage methods and time since harvest [38,45,49–57]. Cooking methods have also been shown to alter phenolic concentrations in virgin olive oil [58,59,60]. Finally, research has shown that the analytical method used to quantify the concentration of phenolic compounds present in virgin olive oil has an influence on the reported concentration [61]. The factors mentioned above are not discussed in the current paper. For an extensive review on the matter, please see the paper by Cicerale and colleagues [62]. Therefore, the objective of the current paper was to review the bioavailability of olive oil phenolic compounds and the biological activities associated with them.

2. Bioavailability of Olive Oil Phenolic Compounds

The bioavailability of a compound refers to the degree in which it is extracted from a food matrix and absorbed by the body [63]. The majority of research regarding the bioavailability of olive oil phenolic compounds has focused on three major phenolics: hydroxytyrosol, tyrosol, and oleuropein, and in general, phenolics from virgin olive oil have been demonstrated to be readily bioavailable. Research has shown that the phenolic compounds, hydroxytyrosol and tyrosol are absorbed after ingestion in a dose-dependent manner [30,64,65]. Tuck and colleagues [66] demonstrated increased bioavailability of hydroxytyrosol and tyrosol when administered as an olive oil solution compared to an aqueous solution. The differences in bioavailability have been suggested to be due to the high antioxidant content of virgin olive oil compared to water and this high antioxidant content may have protected the breakdown of phenolics in the gastrointestinal tract prior to absorption [66]. A further study found that absorption of administered ligstroside-aglycone, hydroxytyrosol, tyrosol, and oleuropein-aglycone was as high as 55–66% in humans [32]. Finally, oleuropein was demonstrated to be somewhat absorbed from isolated perfused rat intestine [67]. The mechanism by which absorption occurs with regards to olive oil phenolic compounds remains unclear. However, the different polarities of the various phenolics has been postulated to play a role in the absorption of these compounds [32]. For instance, the phenolics tyrosol and hydroxytyrosol are polar compounds and their absorption has been postulated to occur via passive diffusion [68]. The polar but larger phenolic, oleuropein-glycoside may be absorbed via a different mechanism to tyrosol and hydroxytyrosol. It has been proposed that oleuropein-glycoside may diffuse through the lipid bilayer of the epithelial cell membrane and be absorbed via a glucose transporter. Two additional mechanisms for oleuropein-glycoside absorption are potentially via the paracellular route or transcellular passive diffusion [67]. The phenolics, oleuropein and ligstroside-aglycones are less polar and currently there is no data available on their mechanism of absorption. Further research is required to substantiate the mechanisms of absorption for these phenolics and further investigate the mechanisms for other phenolic compounds. Studies examining the quantity of phenolics excreted have also been carried out. A low quantity of phenolics present in urine after ingestion would indicate that these phenolics are readily absorbed. Excreted phenolics (mainly in the form of hydroxytyrosol and tyrosol) were determined to be 5–16% of the total ingested [32]. Excretion of approximately 24% of administered tyrosol was demonstrated in a study by Miro-Cases and colleagues [33]. Finally, Visioli and colleagues [30] reported the excretion of administered hydroxytyrosol and tyrosol to be between 30–60% and 20–22% of the total ingested by human subjects, respectively. The above findings demonstrate that humans absorb a significant portion (~40–95%, using hydroxytyrosol and tyrosol as proxy) of the dietary olive oil phenolic compounds they consume [32]. As most of the data is only based on three phenolics, more research is required on the excretion of other key phenolics in virgin olive oil. The metabolism of olive oil phenolic compounds is important in determining their availability. If phenolics are broken down and converted to other phenolics this may have a notable effect on their bioavailability. Phenolic compounds, oleuropein-glycoside and oleuropein and ligstroside-aglycones are converted to hydroxytyrosol or tyrosol and excreted in urine [32]. Hydroxytyrosol and tyrosol themselves are sometimes conjugated to glucuronic acid and excreted in urine as glucuronides [30,32,65,69]. However, further work is needed in this area.

3. Olive Oil Phenolic Compounds and Health

Human and animal research have shown that olive oil phenolic compound’s possess important biological activities that may exert a preventative effect in regards to the development of chronic degenerative diseases. Figure 1 demonstrates the biological activities exerted by olive oil phenolic compounds. Table 1 briefly summarizes the findings of several human studies that have investigated the biological activities of olive oil phenolic compounds.

Figure 1. Biological activities of olive oil phenolic compounds (adapted from Cicerale et al. [62]).

Table 1. Randomized, crossover, controlled, human studies on the effect of olive oil phenolic compounds on biomarkers of health (adapted from Cicerale et al. [62]).

Treatment SubjectNumberPhenolic concentrationStudy designInvestigated biomarkerKey findingsRef.
High phenolic concentration vs. low phenolic concentration olive oil28 coronary heart disease subjects161 vs. 14.67 mg/kg3 week, crossoverIL-6, C-reactive protein, sICAM-1, sVCAM-1and plasma lipidsInterleukin-6 and C-reactive protein decreased after phenol rich olive oil consumption. However, no changes in soluble intercellular (sICAM-1) and vascular adhesion (sVCAM-1) molecules and lipid profile were observed.[70]
High phenolic concentration vs. low phenolic concentration, enriched breakfast21 hyper cholesterol-emic subjects400 vs. 80 mg/kgAcute dose, crossoverFVIIa and PAI-1Concentrations of FVIIa increased less and PAI-1 activity decreased more after the high phenolic breakfast than after the low phenolic breakfast.[71]
High phenolic concentration vs. moderate phenolic concentration vs. poor phenolic concentration olive oil30 healthy subjects825 vs. 370 vs. 0 µmol CAE/kg3 week, crossoverPlasma lipids and oxLDLAn increase in phenolic content of LDL-C and decrease in oxLDL was n