Oleocanthal: Behind the Health Benefits of Olive Oil's Famous Phenol

Since its dis­cov­ery in 1993, oleo­can­thal has become one of the most stud­ied polyphe­nols in extra vir­gin olive oil.

Extra vir­gin olive oil is the only edi­ble oil in which the nat­u­rally occur­ring organic com­pound is found, which research has asso­ci­ated with ben­e­fi­cial impacts on the devel­op­ment of neu­rode­gen­er­a­tive dis­eases, can­cer and other chronic inflam­ma­tory con­di­tions.

Oleocanthal is a monophe­no­lic sec­oiri­doid, a group of antiox­i­dants in some plant-based foods. The rare polyphe­nol is homol­o­gous to ibupro­fen, a non­s­teroidal anti-inflam­ma­tory drug that relieves pain, fever and inflam­ma­tion.

Gary Beauchamp (pro­nounced Beach-um) made this dis­cov­ery after he attended a mol­e­c­u­lar gas­tron­omy con­fer­ence in Sicily in 1999.

The rev­e­la­tion renewed inter­est in the mol­e­cule orig­i­nally known as decar­bomethoxy-dialde­hy­dic ligstro­side agly­cone, which was later renamed by Paul Breslin, one of Beauchamp’s col­leagues, to make the mol­e­cule more mem­o­rable.

He coined oleo­can­thal, deriv­ing the name from oleo for olive oil, canth for sting and al since the mol­e­cule is a dialde­hyde.

Oleocanthal sen­sory attrib­utes

After tast­ing a local extra vir­gin olive oil pro­duced from an attendee’s farm at the 1999 con­fer­ence, Beauchamp noticed that the burn­ing sen­sa­tion he felt in the orophar­ynx, the back of the throat, was the same one elicited by swal­low­ing ibupro­fen in liq­uid form.

Previous research has shown that long-term use of ibupro­fen has demon­strated a reduced inci­dence of can­cer and neu­rode­gen­er­a­tive dis­eases.

Beauchamp imme­di­ately won­dered whether this same sen­sa­tion indi­cated a nat­ural anti-inflam­ma­tory agent in extra vir­gin olive oil and whether this helped explain the well-known health ben­e­fits of the Mediterranean diet.

In the world of extra vir­gin olive oil, there are three pos­i­tive sen­sory char­ac­ter­is­tics: fruity, bit­ter and pun­gent.

The pres­ence of oleo­can­thal in extra vir­gin olive oil con­tributes to its bit­ter­ness. It is the sole source of its pun­gency, man­i­fested as a burn­ing sen­sa­tion in the back of the throat.

The burn­ing asso­ci­a­tion caused by oleo­can­thal is felt in the throat and not the mouth because the sen­sa­tion is medi­ated by TRPA1 ion chan­nel recep­tors located in the throat, nasal cav­ity and else­where in the body, but not the mouth.

Oleocanthal and health

Oleocanthal’s health ben­e­fits are pri­mar­ily asso­ci­ated with the compound’s anti-inflam­ma­tory prop­er­ties, which Beauchamp and a research team found slightly more potent than ibupro­fen.

Research has found that the con­cen­tra­tion of oleo­can­thal in extra vir­gin olive oil is roughly 284 to 711 mil­ligrams per kilo­gram.

Typical Mediterranean pop­u­la­tions are esti­mated to con­sume 25 to 30 mil­li­liters of extra vir­gin olive oil daily, mean­ing the daily oleo­can­thal con­sump­tion would be between 6.5 and 19.6 mil­ligrams. By com­par­i­son, 10 mil­ligrams of oleo­can­thal is con­sid­ered a low dose of ibupro­fen.

Oleocanthal’s anti-inflam­ma­tory activ­ity comes from its abil­ity to inhibit an enzyme called cyclooxy­ge­nase, which forms sub­stances called prostanoids. The for­ma­tion of these sig­nal­ing mol­e­cules causes inflam­ma­tion.

As a result, the con­sump­tion of extra vir­gin olive oil high in oleo­can­thal has been asso­ci­ated with pos­i­tive impacts on a range of inflam­ma­tion-related chronic dis­eases.

Oleocanthal and demen­tia

Due to ibuprofen’s well-known asso­ci­a­tion with ben­e­fi­cial effects on mark­ers of neu­rode­gen­er­a­tive dis­ease, researchers were nat­u­rally eager to inves­ti­gate the role of oleo­can­thal on neu­rode­gen­er­a­tive dis­ease, espe­cially demen­tia.

Numerous stud­ies have found that oleo­can­thal inter­feres with the aggre­ga­tion of Amyloid beta pro­tein in the brain, which is found in peo­ple with Alzheimer’s dis­ease, the most com­mon type of demen­tia.

Mice treated with oleo­can­thal for four weeks were found to have sig­nif­i­cantly reduced amounts of Amyloid beta pro­tein in sev­eral parts of the brain.

Researchers hypoth­e­sized that this may be due to oleocanthal’s abil­ity to increase the expres­sion of two pro­teins (P‑glycoprotein and LRP1) that clear Amyloid beta pro­tein from the blood-brain bar­rier.

In a sep­a­rate study, researchers found that oleo­can­thal also induces antiox­i­dant effects in the brain, which resulted in the decrease of a cytokine known to con­tribute to neu­roin­flam­ma­tion.

The same study also sug­gested that oleo­can­thal pro­tects neu­rons from Amyloid beta pro­tein-induced dete­ri­o­ra­tion and oxida­tive stress, which is a sig­nif­i­cant part of the patho­phys­i­o­log­i­cal process of demen­tia.

Furthermore, a 2021 study from researchers at the University of Louisiana-Monroe found that oleo­can­thal con­sump­tion deac­ti­vates the com­ple­men­tary pep­tide C3a recep­tor 1 (C3AR1).

In patients with Alzheimer’s dis­ease and those at risk of Alzheimer’s dis­ease, this recep­tor over­works, pro­mot­ing inflam­ma­tion and impair­ing the immune sys­tem from clear­ing away dam­aged cells that con­tribute to the devel­op­ment of demen­tia.

Oleocanthal and can­cer treat­ment

There is a grow­ing body of research, includ­ing many in vitro stud­ies, inves­ti­gat­ing the role of phe­no­lic com­pounds in slow­ing the spread of can­cer, with oleo­can­thal thought to play a lead­ing role.

COX2, a cyclooxy­ge­nase enzyme, is impli­cated in the devel­op­ment and spread of sev­eral types of can­cer both in human and ani­mal stud­ies. Oleocanthal’s abil­ity to reduce the inten­sity of this cyclooxy­ge­nase enzyme has made the phe­no­lic com­pound a topic of inter­est among all types of can­cer researchers.

Since 2020, the National Cancer Institute in the United States has iden­ti­fied oleo­can­thal as a poten­tial nutraceu­ti­cal in the fight against can­cer, specif­i­cally breast can­cer.

A 2021 study from the University of Louisiana-Monroe found that oleo­can­thal may be effec­tive as part of a tar­geted ther­apy for triple-neg­a­tive breast can­cer (TNBC) patients.

Using advanced pre­clin­i­cal trans­genic mouse mod­els – human can­cer cells trans­planted into immun­od­e­fi­cient mice – the researchers found that oleo­can­thal con­sump­tion sup­pressed tumor growth.

Separate research pub­lished in Spain delved fur­ther into the mech­a­nisms by which oleo­can­thal may have achieved these results. The 2023 study found that oleo­can­thal and olea­cein dis­rupted the process of angio­gen­e­sis, the devel­op­ment of blood cells to sup­ply nutri­ents to tumors, both in vivo and in vitro.

Meanwhile, a 2022 study pub­lished by researchers in Greece found that leukemia patients con­sum­ing oleo­can­thal and olea­cein expe­ri­enced a decrease in white blood cell pro­duc­tion through a process known as apop­to­sis, a mech­a­nism of cell death that can kill can­cer cells.

Oleocanthal and car­diometa­bolic dis­ease

While oleo­can­thal has mainly been asso­ci­ated with ben­e­fi­cial impacts on can­cer and neu­rode­gen­er­a­tive dis­eases, new research sug­gests that the polyphe­nol also improves the health of peo­ple suf­fer­ing from chronic car­diometa­bolic dis­eases, includ­ing obe­sity and dia­betes.

A 2023 study pub­lished by researchers in Spain found that con­sum­ing extra vir­gin olive oil rich in oleo­can­thal and olea­cein increased blood antiox­i­dant defenses and decreased oxida­tive stress and inflam­ma­tion para­me­ters.

Oxidative stress is widely believed to pre­cede the devel­op­ment of inflam­ma­tion, which is related to insulin resis­tance. The research showed that con­sum­ing extra vir­gin olive oil rich in the two polyphe­nols may pre­vent the devel­op­ment of dia­betes.

Other health ben­e­fits asso­ci­ated with oleo­can­thal

Due to oleocanthal’s marked sim­i­lar­i­ties with ibupro­fen, researchers are inves­ti­gat­ing the poten­tial of the mol­e­cule to mit­i­gate a range of dis­eases treated by the med­ica­tion.

As of 2019, a com­bined 546 mil­lion peo­ple world­wide are liv­ing with either osteoarthri­tis or rheuma­toid arthri­tis. Both con­di­tions are aggra­vated by the pro­duc­tion of pro-inflam­ma­tory cytokines that increase nitric oxide and prostaglandin pro­duc­tion and syn­the­size the enzymes that degrade car­ti­lage in the joints.

Several stud­ies have found that through its inhi­bi­tion of cyclooxy­ge­nase, oleo­can­thal atten­u­ates the symp­toms asso­ci­ated with cytokine inflam­ma­tion and reduces the pro­duc­tion of nitric oxide and prostaglandins. As a result, oleo­can­thal has been posited as a poten­tially effec­tive treat­ment against both types of arthri­tis.

Other research in Spain found that con­sum­ing extra vir­gin olive oil rich in polyphe­nols, includ­ing oleo­can­thal, may also help heal dam­aged skin.

The 2023 study demon­strated that con­sump­tion of oleo­can­thal helps stim­u­late fibrob­last pro­duc­tion. Fibroblasts are the cells in the skin respon­si­ble for regen­er­a­tion and repair­ing dam­aged skin.

The future of oleo­can­thal research

While a grow­ing body of research demon­strates oleocanthal’s pos­i­tive health impacts and the poten­tial use cases, there has been lim­ited progress in devel­op­ing an oleo­can­thal-based nutraceu­ti­cal.

According to Beauchamp, this is largely because no one owns a patent on the mol­e­cule. As a result, drugs pro­duced from oleo­can­thal could be copied by any­one, mean­ing a phar­ma­ceu­ti­cal com­pany could not recoup its invest­ment in research and devel­op­ment.

Another lim­i­ta­tion cited by Beauchamp is that oleo­can­thal can only be obtained by degrad­ing extra vir­gin olive oil. The quan­tity of oil required to yield the nec­es­sary amounts would be costly.

For the fore­see­able future, the best way to obtain the ben­e­fits of oleo­can­thal remains to con­sume high-qual­ity extra vir­gin olive oil.

• International Journal of Molecular Sciences
• American Scientist
• Science Direct