Oleacein: The Promising Phenolic Compound in Extra Virgin Olive Oil

Summary

Oleacein, a phe­no­lic com­pound found in extra vir­gin olive oil, has antiox­i­dant, anti-inflam­ma­tory, and poten­tial anti-ath­er­o­scle­rotic prop­er­ties that can sig­nif­i­cantly impact human health. Research shows that olea­cein is one of the most abun­dant and chem­i­cally active phe­no­lics in vir­gin olive oils, with the poten­tial to improve meta­bolic health, pro­tect the brain, and reduce inflam­ma­tion in the body. Studies are ongo­ing to fur­ther under­stand olea­cein’s absorp­tion, metab­o­lism, and bioavail­abil­ity, and con­sumers inter­ested in its ben­e­fits should look for high-qual­ity olive oils with a high polyphe­nol count.

Among the many ben­e­fi­cial com­po­nents of extra vir­gin olive oil, few are as promis­ing and as lit­tle known as olea­cein.

Initial research shows that the antiox­i­dant, anti-inflam­ma­tory and poten­tial anti-ath­er­o­scle­rotic prop­er­ties of this phe­no­lic com­pound may sig­nif­i­cantly impact human health.

Most health-con­scious con­sumers are famil­iar with antiox­i­dants, includ­ing hydrox­y­ty­rosol or flavonoids, due to decades of research on the com­pounds.

Due to its unique nature, research on olea­cein began rel­a­tively recently. It was ini­tially dis­cov­ered and iso­lated in olive leaves, and its role in extra vir­gin olive oil was not imme­di­ately evi­dent.

According to the researchers study­ing this mol­e­cule, olea­cein is both one of the most abun­dant phe­no­lics in vir­gin olive oils and one of the most chem­i­cally active.

Where does olea­cein come from?

Oleacein is found almost exclu­sively in high-qual­ity, fresh extra-vir­gin olive oil and results from trans­for­ma­tions that occur dur­ing olive pro­cess­ing.

“Oleacein orig­i­nates from the hydrol­y­sis of the gly­co­side oleu­ropein,” Maria de Fátima Paiva-Martins, researcher at the University of Porto’s chem­istry and bio­chem­istry depart­ment, in Portugal, told Olive Oil Times.

Hydrolysis is a chem­i­cal reac­tion in which com­plex sub­stances, such as pro­teins or fats, are split into sim­pler ones.

During the olive crush­ing process, oleu­ropein under­goes enzy­matic hydrol­y­sis, which pro­duces agly­cone, a more fat-sol­u­ble mol­e­cule. ​“This agly­cone then trans­forms into olea­cein,” Fátima Paiva-Martins said.

Where hydrox­y­ty­rosol and olea­cein meet

One of the most inter­est­ing com­po­nents of extra vir­gin olive oil, hydrox­y­ty­rosol, is not present in high amounts in olive oil.

Instead, it is a metabo­lite, a byprod­uct that appears in the human body after ingest­ing com­pounds, includ­ing olea­cein.

“Hydroxytyrosol is highly hydrophilic, so it doesn’t remain in the olive oil. What we find in higher con­cen­tra­tions are its esters, like olea­cein, which later hydrolyze into hydrox­y­ty­rosol after diges­tion,” Fátima Paiva-Martins said.

Extra vir­gin olive oil’s phe­nol esters are com­pounds formed when a phe­nol (such as hydrox­y­ty­rosol) reacts with spe­cific acid mol­e­cules.

“Oleacein is a biphe­no­lic com­pound. It con­tains two phe­no­lic hydroxyl groups, which makes it an espe­cially pow­er­ful antiox­i­dant,” said Prokopios Magiatis, an asso­ciate pro­fes­sor of phar­ma­cog­nosy at the National and Kapodistrian University of Athens.

“It’s an ester of hydrox­y­ty­rosol, but unlike hydrox­y­ty­rosol, which is water-sol­u­ble, olea­cein is amphiphilic. It can dis­solve in both water and fat,” he added.

Oleacein’s vast poten­tial in health

Oleacein’s dual sol­u­bil­ity may help explain its effec­tive­ness inside the human body, as it allows broad inter­ac­tion with both lipid and aque­ous envi­ron­ments.

Because of its struc­ture, olea­cein can inte­grate into the body’s lipid par­ti­cles, includ­ing low-den­sity lipopro­teins (LDL), often known as ​“bad cho­les­terol.” Once incor­po­rated, it might offer a pro­tec­tive shield.

“Oleacein can be incor­po­rated in LDL par­ti­cles and pro­tect them from oxi­da­tion,” Magiatis explained. ​“And that is cru­cial, because the oxi­da­tion of LDL cho­les­terol is one of the first steps in the for­ma­tion of arte­r­ial plaques.”

Oleacein also shows promis­ing anti-inflam­ma­tory prop­er­ties. Its mech­a­nisms are quite dif­fer­ent from those of bet­ter-known com­pounds, such as oleo­can­thal, which is also found in extra vir­gin olive oil.

“Oleacein does not inhibit COX,” Magiatis remarked, refer­ring to the cyclooxy­ge­nase enzymes that oleo­can­thal tar­gets, and which are respon­si­ble for pro­duc­ing prostaglandins, mol­e­cules that pro­mote inflam­ma­tion and pain.

“But olea­cein reduces the expres­sion of TNF‑α and cer­tain inter­leukins. These are cytokines that drive the inflam­ma­tory response,” Magiatis said.

Cytokines are small pro­teins that act as mes­sen­gers between cells in the body. Therefore, olea­cein mod­u­lates the body’s sen­si­tiv­ity and reac­tion to inflam­ma­tory mol­e­cules.

“It can also sup­press enzymes involved in inflam­ma­tion. So we’re see­ing a com­ple­men­tary mode of action,” Magiatis said.

Oleacein’s health impacts may also extend to metab­o­lism.

According to a clin­i­cal study pub­lished in 2024, 17 pre-dia­betic adults con­sumed extra vir­gin olive oil rich in olea­cein and oleo­can­thal.

The results, com­pared to a stan­dard olive oil, were sig­nif­i­cant, as inflam­ma­tory cytokines dropped, antiox­i­dant sta­tus improved, lipid oxi­da­tion decreased, and both body mass index and glu­cose sig­nif­i­cantly enhanced.

The researchers con­cluded that olea­cein-rich olive oil can con­tribute to improved meta­bolic health in indi­vid­u­als at high risk.

Oleacein in brain health research

Given its broad impli­ca­tions in the body’s chem­istry, research has recently focused on how olea­cein impacts brain func­tion.

Several neu­rol­ogy stud­ies in cell cul­tures and ani­mal mod­els have demon­strated that olea­cein might play a role in pro­tect­ing the brain.

Magiatis’s lab, in col­lab­o­ra­tion with researchers at the University of Valladolid in Spain, tested olea­cein in an ani­mal model of mul­ti­ple scle­ro­sis.

“It was very clear: olea­cein pro­tected the brain. We saw anti-inflam­ma­tory activ­ity in nerve cells and strong antiox­i­dant effects at the site of the dam­age,” Magiatis explained.

That pre­clin­i­cal study laid the ground­work for a human clin­i­cal trial in patients with mul­ti­ple scle­ro­sis, which has now been com­pleted and is await­ing pub­li­ca­tion.

Meanwhile, other groups are explor­ing oleacein’s neu­ro­pro­tec­tive poten­tial.

A 2023 paper demon­strated that olea­cein acts as a TrkB recep­tor ago­nist, thereby pro­mot­ing the expres­sion of brain-derived neu­rotrophic fac­tor, a key pro­tein involved in neu­ro­plas­tic­ity.

The authors noted reduced depres­sive behav­ior and inflam­ma­tion in mice treated with olea­cein.

The jour­ney has just begun

While olea­cein is at the fore­front of research on extra vir­gin olive oil’s most active phe­nols, Magiatis and Fátima Paiva-Martins said research is still in its early stages.

Much of what is known today about oleacein’s impact comes from lab and ani­mal mod­els, and although human stud­ies are emerg­ing, much remains to be explored.

“The bio­log­i­cal effects attrib­uted to olive oil con­sump­tion are essen­tially due to the intake of lipophilic deriv­a­tives of oleu­ropein, such as olea­cein,” Fátima Paiva-Martins noted.

“The metabo­lites respon­si­ble for oleacein’s bio­log­i­cal activ­ity have not yet been fully iden­ti­fied or char­ac­ter­ized,” the researcher cau­tioned. ​“We know hydrox­y­ty­rosol metabo­lites play a role, but the full pic­ture remains unknown.”

“Oleacein is a highly reac­tive mol­e­cule and can form adducts with pro­teins, though the impact of this reac­tiv­ity on its bio­log­i­cal activ­ity and the sys­temic effects observed after olive oil con­sump­tion is still not fully under­stood,” she added.

Research is ongo­ing, focus­ing on the com­plex­ity of olea­cein.

“We’re in a good place,” Magiatis said. ​“We have made progress, and soon new research will clar­ify key aspects such as oleacein’s absorp­tion, metab­o­lism and bioavail­abil­ity.”

How to select EVOO high in olea­cein

Current knowl­edge about olea­cein sug­gests that con­sumers inter­ested in its ben­e­fits should look for high-qual­ity olive oils with a high polyphe­nol count.

Freshly pro­duced olive oils that pro­voke a slight cough or a pep­pery kick are good can­di­dates for deliv­er­ing olea­cein, as such sen­sory irri­ta­tion is often a sign of both olea­cein and oleo­can­thal.

Besides stor­ing extra vir­gin olive oil in a cool, dark place, research sug­gests that olea­cein lev­els can be well pre­served at wine-cel­lar tem­per­a­tures (12 to 14 °C).

According to Magiatis, what makes the dif­fer­ence in the healthy impact of extra vir­gin olive oil is not a sin­gle sig­nif­i­cant com­po­nent, but rather the whole prod­uct.

“In my per­sonal view, olive oil is the best way to get those healthy com­pounds in your body,” he said. ​“It is nat­ural, bal­anced, and it comes with dozens of other com­pounds that work together. Nothing can com­pare to that.”