Cardioprotective and Anti-inflammatory Properties of Olive Oil Phenolic Compounds

Cardiovascular (CV) diseases are the leading cause of world mortality, with 7.4 million of their 17.7 million annual deaths due to coronary artery disease (CAD). CAD risk factors include diabetes mellitus (diabetes type 2 [DT2]), hypertension, dyslipidemia, obesity, poor diet, tobacco (Nicotiana tabacum, Solanaceae) smoking, lack of exercise, and alcohol abuse. Acute myocardial infarction and death—two primary effects associated with CAD—account for more than 90% of all CAD-related outcomes. Atherosclerotic plaques form when vascular endothelial cells express chemotactic and adhesion molecules, starting the inflammatory process crucial to CAD’s pathogenesis. Within a healthy diet, cardioprotective foods can modulate expression of proinflammatory cytokines and inflammation markers and help control risk factors like DT2, hypertension, dyslipidemia, and obesity. Phenolic compounds and unsaturated fats found in olive (Olea europaea, Oleaceae) oil (OO) show benefits in this area and may improve CV outcomes overall. Virgin OO (VOO) is produced by mechanical processes alone, while refined OO (ROO) is subjected to mechanical and chemical processes. This influences the concentration of phenolic compounds, with extra VOO (EVOO) retaining significantly more phenolics than ROO, while both oils have similar fatty acid content. VOOs are divided into EVOO, virgin (fine), and lampante according to the amount of acidity (ratio of free fatty acids to total oleic acid) as follows: ≤0.8%, ≤2%, and >2%, respectively). EVOO’s sensory and physicochemical properties are superior to those of other VOOs.

VOOs have saponifiable and unsaponifiable fractions; the former about 98% of total content, with monounsaturated oleic acid comprising 55-83% of that fraction. VOOs also have polyunsaturated fatty acids, such as linoleic acid (3.5-21%), and saturated fatty acids, like palmitic (7.5-20%) and stearic acids (0.5-5%). Unsaponifiable fractions, 1-2% of total content, include over 230 compounds, such as sterols, hydrocarbons, volatile molecules, triterpenic and aliphatic alcohols, pigments, and phenolics. The latter, secondary metabolites created during plant development or under stress, occur when fruits are crushed for oil extraction. Their presence is directly related to glycosides in fruit tissue and both hydrolytic and oxidative enzymes. Structurally, they have one or more hydroxyl and an aromatic ring. Phenolic compounds may be lipophilic or hydrophilic. Among lipophilic compounds in VOO, α-tocopherol is most important, with a mean level of 150.7 mg/kg, up to 400 mg/kg. At least 36 hydrophilic compounds in OO are grouped into six categories by chemical structure; these are not described. VOO phenolic content varies with cultivar, growth location (altitude), maturity at harvest, fruit storage conditions, oil extraction procedures, and commercial storage.*

Phenolics are mostly responsible for organoleptic qualities of olive fruit and OO’s oxidative stability. Hydroxytyrosol (HT; 3,4-DHPEA) and its derivatives, including oleuropein complex, tyrosol (p-HPEA), and especially the secoiridoid derivatives (dialdehyde forms of decarboxymethyl elenolic acid linked to HT [oleacein; 3,4-DHPEA-EDA] and tyrosol [oleocanthal; p-HPEA-EDA], aglycones of oleuropein [3,4-DHPEA-EA], and ligstroside [p-HPEA-EA]), are the most abundant phenolics in OO (90% of phenolic content). HT and tyrosol are the primary phenols responsible for producing VOO’s antiatherosclerotic effects. Aglycones of oleuropein, created by hydrolysis during fruit maturation, oil extraction, and storage, are in part responsible for EVOO’s complex flavors. Lignans also occur at high levels. Phenolic acids, the first compounds identified in OO with at least 14 described,** usually occur at <1 mg/kg. Flavones luteolin and apigenin, OO’s main flavonoids, also occur at relatively low levels. Hydroxy-isocromans have been found in commercial VOOs, formed from HT’s reactions with benzaldehyde and vanillin. Phenolic alcohols also occur. Phenolic compounds are metabolized after ingestion, first by hydrolysis in the stomach and small intestine, then by conjugation by gut microbiota in the small intestine and enzymatically in the liver. Oleuropein, however, is metabolized by colonic microbiota to HT. In a rather startling study cited of OO absorption in healthy subjects, a group who had received ileostomies and another group with intact colons were included. OO absorption was estimated at 55-66% of the total dose, with no difference stated between groups. Absorption of HT varies with the food matrix. It is noted that supplementation with OO is associated with other changes in dietary patterns, including consumption of other phenolic-rich foods with compounds that may influence phenolic absorption, affect gut microbiota, and themselves modify CAD risk factors.

In vitro and in vivo studies report benefits of phenolic compounds in general and OO compounds specifically against inflammation. Human primary prevention studies show an association between daily EVOO intake and reduced risk of major CV events in at-risk patients; consumption of 50 mL/day EVOO cut risks of CAD by 37%, and of major CV events by 30%. Anti-inflammatory effects of EVOO have been seen at different stages of atherosclerosis. They include modulation of the arachidonic acid cascade, effects on signaling pathways and receptors, improvement of vascular function, and reduced cytokines and adhesion molecules. In some studies, EVOO has been combined or compared with other anti-inflammatory foods (including the “Mediterranean diet”) or with other OOs and/or dietary oils. Most report the superiority of EVOO with high HT. Short-term studies show less definite benefits, but one study with seven weeks of supplementation found ongoing benefits in reduced inflammatory markers at five years’ follow-up. Most trials have been quite small; the largest population shown was 82 subjects. More long-term trials, specifically in established CAD, would be useful. Evidence for EVOO’s benefits against CAD is strong, and its lack of any toxicity makes clinical use compelling.

* While unmentioned by these authors, post-purchase storage and use of OO is crucial to the quality of OO consumed dietarily. Light and/or heat quickly degrade OO’s phenolic and fatty acid contents.

** But just 12 are listed in an accompanying table. 


Souza PAL, Marcadenti A, Portal VL. Effects of olive oil phenolic compounds on inflammation in the prevention and treatment of coronary artery disease. Nutrients. 2017;9(10):1087. doi: 10.3390/nu9101087.