In January 2021, a new study was published titled «Spontaneous In Vitro and In Vivo Interaction of Oleocanthal with Glycine in Biological Fluids: Novel Pharmacokinetic Markers».

This particular publication was made by the following scientists: Lucy I. Darakjian, Aimilia Rigakou, Andrew Brannen, Mohammed H. Qusa, Niki Tasiakou, Panagiotis Diamantakos, Miranda N. Reed, Peter Panizzi, Melissa D. Boersma, Eleni Melliou, Khalid A. El Sayed, Prokopios Magiatis, and Amal Kaddoumi. It was published in ACS Pharmacology & Translational Science on January 5, 2021 (ACS Pharmacol. Transl. Sci. 2021, 4, 1, 179–192).

This publication is about the discovery of the way in which oleocanthal, when entering our body, is transformed into an active form through a specific mechanism, which can quickly reach even the brain.

Since the first discovery of its ibuprofen-like anti-inflammatory activity in 2005, the olive phenolic oleocanthal gained great scientific interest and popularity due to its reported health benefits.

Oleocanthal is a monophenolic secoiridoid exclusively occurring in extra-virgin olive oil (EVOO). While several groups have investigated oleocanthal pharmacokinetics and disposition, none was able to detect oleocanthal in biological fluids or identify its pharmacokinetic profile that is essential for translational research studies. Besides, oleocanthal could not be detected following its addition to any fluid containing amino acids or proteins such as plasma or culture media, which could be attributed to its unique structure with two highly reactive aldehyde groups.

Here, the scientists demonstrated that oleocanthal spontaneously reacts with amino acids, with high preferential reactivity to glycine compared to other amino acids or proteins, affording two products: an unusual glycine derivative with a tetrahydropyridinium skeleton that is named oleoglycine, and according to their collective data, the plausible formation of tyrosol acetate as the second product.

They performed extensive studies to validate and confirm oleocanthal reactivity, which were followed by pharmacokinetic disposition studies in mice, as well as cell culture transport studies to determine the ability of the formed derivatives to cross physiological barriers such as the blood-brain barrier. Thus, they showed for the first time that oleocanthal is biochemically transformed to novel products in amino acids/glycine-containing fluids, which were successfully monitored in vitro and in vivo, creating a completely new perspective to understand the well-documented bioactivities of oleocanthal in humans.

The blood-brain barrier intervenes between the blood and the central nervous system (brain and spinal cord). It serves to maintain the extracellular fluid environment to ensure optimal neuron functionality. The movement of large molecules and other substances, including many drugs, from the blood to the interstitial space of the central nervous system is limited by the blood-brain barrier.

Only some small molecules (water; certain gases such as oxygen and carbon dioxide) and lipid-soluble substances (such as small fatty acids) can move passively through the barrier (European Journal Science in School - Guardian of the brain: the blood-brain barrier, 2018). 

Many studies have shown the link between the disruption of the blood-brain barrier and other neurological diseases, including stroke, epilepsy, multiple sclerosis, Alzheimer’s disease and Parkinson’s disease (European Journal Science in School - Guardian of the brain: the blood-brain barrier, 2018). 

The bioactivity and action of oleocanthal have been the subject of study by many scientific groups for decades. Listed below are some detailed scientific studies regarding the action of oleocanthal, with their respective sources.

• Oleocanthal seems to have an anti-inflammatory effect similar to Ibuprofen (Phytochemistry: Ibuprofen-like activity in extra-virgin olive oil. Beauchamp, Gary K. et al. Nature (2005), 437(7055), 45-46).

• Oleocanthal  seems to have a positive effect on Alzheimer's, slowing down the disease(“Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-β load and related toxicity in a mouse model of Alzheimer's disease” Batarseh YS, Kaddoumi A., J Nutr Biochem. 2018 May;55:113-123).

• Oleocanthal rich olive oils help reduce blood clots (Journal of Functional Foods 36 (2017) 84-93).

• Beneficial effect of oleocanthal against malignant melanoma of the skin (Nutr Cancer. 2016 Ju;68(5):873-7).

• Oleocanthal and its derivatives act against inflammatory diseases of the joints (Arthritis Rheum. 2010 Jun;62(6):1675-82).

• Oleocanthal has a beneficial effect on melanoma (Oncol Rep. 2017 Jan;37(1):483-491).

• Daily consumption of olive oil rich in oleocanthal and oleacin seems to have a positive effect in patients with Chronic Lymphocytic Leukemia(Effect of Dietary Intervention With High-Oleocanthal and Oleacin Extra Virgin Olive Oil in Patients With Chronic Lymphocytic Leukemia a Pilot Study – Interventional Clinical Trial 2018/2019)

• According to the Professor of the Department of Pharmacognosy and Natural Products Chemistry of UOA, Mr. Magiatis Prokopis, "Chronic exposure to low doses of antioxidants / anti-inflammatory substances such as oleocanthal, offers protection against cardiovascular disease and aging." Also, "Oleocanthal is responsible for the pungency that is characteristic of unripe olive oil." (INGREDIENTS OF OLIVE OIL WITH SPECIAL IMPORTANCE FOR OXIDATIVE STRESS AND HEALTH, UOA, Presentation 2015)

Nick Sakellaropoulos
Chemical Engineer M.Sc.
Production Manager
Sakellaropoulos Organic Farms

Sources

• Spontaneous In Vitro and In Vivo Interaction of (−)-Oleocanthal with Glycine in Biological Fluids: Novel Pharmacokinetic Markers , ACS Pharmacol. Transl. Sci. 2021, 4, 1, 179–192

• Magiatis P., Ingredients of olive oil with special importance for oxidative stress and health, EKPA, Presentation, 2015

• Andrea Paola Rojas Gil et al., Effect of Dietary Intervention With High-Oleocanthal and Oleacin Extra Virgin Olive Oil in Patients With Chronic Lymphocytic Leukemia a Pilot Study, Interventional Clinical Trial, 2019.

• Gu Y., et al., Oleocanthal exerts anti-melanoma activities and inhibits STAT3 signaling pathway, Oncol Rep. 2017 Jan;37(1):483-491. doi: 10.3892/or.2016.5270. Epub 2016 Nov 23.

• Iacono A. et al., Effect of oleocanthal and its derivatives on inflammatory response induced by lipopolysaccharide in a murine chondrocyte cell line. Arthritis Rheum. 2010 Jun;62(6):1675-82. doi: 10.1002/art.27437.

• Fogli S. et al., Cytotoxic Activity of Oleocanthal Isolated from Virgin Olive Oil on Human Melanoma Cells,Nutr Cancer. 2016 Jul;68(5):873-7

• Karan Agrawal, et al.,Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial Journal of Functional Foods 36 (2017) 84-93

• Batarsheh YS, Kaddoumi A, Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-β load and related toxicity in a mouse model of Alzheimer's disease, J Nutr Biochem. 2018 May;55:113-123. doi: 10.1016/j.jnutbio.2017.12.006. Epub 2017 Dec 27.

• Beauchamp GK. Et al (2005) Phytochemistry: ibuprofen-like activity in extra-virgin olive oil. Nature 2005 Sep 1;437(7055):45-6.

• Yun Jiang, Guardian of the brain: the blood-brain barrier, European Journal Science in School 2018 (Issue 42)