- 1 Oleuropein and its Dual Mechanism
- 2 Insulin and Amylin
- 3 What is Oleiropein ?
- 4 Bio-chemical based Health Benefits of Olives Products
- 5 Alzheimer’s Disease
- 6 Anti-cancer and mTOR effects
- 7 Anti-inflammation and pain
- 8 Specific Olive Health promoting Indications
- 9 Discussion
- 10 Does the processing of olives remove oleuropein ?
- 11 Conclusion
- 12 Reference Note
- 13 Share this:
- 14 Like this:
- 15 Related
One of the reasons the Mediterranean Diet is so healthful centers on the mellenia old Olive Tree and its fruits: leaves, olives and olive oil. In addition to Olives’ Heart benefits, recent Science has elucidated one of its key molecules, oleuropein, and uncovered two of its mechanisms that modulate both blood sugar and detoxification. In this blog-article, i will briefly sum up this new discovery (Section A) and follow-up with a synthesis of a few of the many heart and other health benefits of this superfoodsa Mediterranean tree (Section B).
Oleuropein and its Dual Mechanism
Insulin and Amylin
According to Virginia Tech research team, (Source). the olive-derived compound oleuropein was recently shown to help the body modulate insulin and amylin. Insulin is a central signaling molecule in the body that controls metabolism. If was found that oleuropein fortifies this important hormone.
As for amylin, it was also demonstrated that this same oleuropein detoxifies this signaling molecule. Amylin tends to over-produce, because of which it forms harmful aggregates in type 2 diabetes. Oleuropein modultes this process. In these two distinct ways, oleuropein helps prevent the onset of diseases.
These findings were recently published in the journal Biochemistry as a Rapid Report, a medium which is reserved for timely topics of unusual interest (Source). (1)
“Our work provides new mechanistic insights into the long-standing question of why olive products can be anti- diabetic,” said Bin Xu, lead author, assistant professor of biochemistry in the College of Agriculture and Life Sciences. “We believe it will not only contribute to the biochemistry of the functions of the olive component oleuropein, but also have an impact on the general public to pay more attention to olive products in light of the current diabetes epidemic.” (Source)
What is Oleiropein ?
Oleuropein is a rare glycosylated seco-iridoid, a type of phenolic bitter compound found in green olives, olive leaves as well as argan oil (2). A while back, laboratory research found that oleuropein had activity as an agonist of the G-protein (3) as well as estrogen receptor. (4). Pending basic research that is still better examining whether oleuropein and other olive polyphenols have useable pharmacological properties (5), in holistic medicine, we already know that the Olive tree has bestwoed upon humans and animals multiple medicinal virtues.
Bio-chemical based Health Benefits of Olives Products
There are many health promoting compounds in olive products, one of which are olive phenolics. which are much more concentrated in the leaves compared with olive fruit or olive oil: 1450 mg total phenolics/100 g fresh leaf vs. 110 mg/100 g fruit and 23 mg/100 ml extra virgin olive oil, phenolics are anti-inflammatory and helo to modulate blood pressure. (6)
Another major olive active compounds in unprocessed olive leaf are oleuropein and hydroxytyrosol (7), as well as polyphenols and flavonoids, including luteolin, rutin, caffeic acid, catechin and apigenin and elenolic acid. Elenolic acid is a component of olive oil and olive leaf extract. It can be considered as a marker for maturation of olives (8).
Still another health promoting Oive compound is Oleocanthal. A phenylethanoid, (a type of natural phenolic compound found in extra-virgin olive oil) oleocanthal appears to be responsible for the burning sensation that occurs in the back of the throat when consuming such oil. Oleocanthal is a tyrosol ester and its chemical structure is related to oleuropein. It has positive effects for Alzheimer’s diseas as well as cancer.
Oleocanthal can reduce the accumulation of β-amyloid proteins involved in Alzheimer’s Disease, via up-regulation of P-glycoprotein and LRP1 (9).
Anti-cancer and mTOR effects
Oleocanthal is capable of killing a variety of human cancer cells in vitro while leaving healthy cells unharmed. (10). While apoptosis generally requires between 16 and 24 hours, oleocanthal operated within 30 minutes to one hour. Oleocanthal pierces cancer cells’ lysosomes, the containers that store the cell’s waste products, releasing enzymes that kill the cell. In healthy cells, the application of oleocanthal caused a temporary halt in their life cycles, but after 24 hours they returned to normal. (11).
Oleocanthal inhibits the enzymatic activity of mammalian target of rapamycin (mTOR) with an IC50 value of 708 nM. (12) Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose-dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA-MB-231). These results strongly indicate that mTOR inhibition is at least one of the factors of the reported anticancer and neuroprotective properties of oleocanthal. (13).
Anti-inflammation and pain
Furthermore, in addition to its anti-inflammatory and antioxidant properties, oleocanthal was found to mimick classical non-steroidal anti-inflammatory drugs, in that it showed to be a non-selective inhibitor of cyclooxygenase (COX). 50 g (more than three and a half tablespoons) of a typical extra virgin olive oil per day contains an amount of oleocanthal with similar in vitro anti-inflammatory effect as 1/10 of the adult ibuprofen dose (14).
Specific Olive Health promoting Indications
Olive leaf extracts offer similar protection for neurodegenerative diseases. Oxidative stress occurs more gradually in neurodegenerative diseases. However, the effects add up over a lifetime, producing inflammation and other changes that result in the accumulation of abnormal proteins that interfere with brain function and kill neurons. Olive leaf extracts help prevent these abnormal proteins from assembling into the neurofibrillary tangles seen in the brains of people with Alzheimer’s and similar diseases.54-56
Olive leaves and their extracts have long been used in the Mediterranean as folk remedies for arthritis. Now, scientific evidence has proven that olive leaf extracts can in fact interfere with the development of several different kinds of arthritis, including gout, rheumatoid arthritis, and osteoarthritis.
Gout is caused by the accumulation of uric acid crystals in joints, the byproducts of impaired recycling of DNA and RNA in cells. In a mechanism identical to that of allopurinol (the gold standard drug therapy for gout), oleuropein prevents the buildup of uric acid by inhibiting xanthine oxidase, the enzyme responsible for converting DNA and RNA into uric acid.57
Oleuropein has also been found to help prevent and treat symptoms of rheumatoid arthritis. When administered at the earliest sign of arthritis in animal models, oleuropein prevented symptoms from developing and also produced marked improvement in the microscopic appearance of joint tissue from affected animals. When administered after arthritis was fully developed, there was significant improvement in inflammatory changes to joints, compared with untreated animals.58
Oleuropein had similar benefits on osteoarthritis. In animal models of this degenerative joint disease, olive leaf extract improved joint swelling, improved the microscopic appearance of joint tissue, and prevented the production of inflammatory cytokines.59
Bazoti FN, Bergquist J, Markides KE, Tsarbopoulos A. Noncovalent interaction between amyloid-beta-peptide (1-40) and oleuropein studied by electrospray ionization mass spectrometry. J Am Soc Mass Spectrom. 2006 Apr;17(4):568-75.
55Daccache A, Lion C, Sibille N, et al. Oleuropein and derivatives from olives as Tau aggregation inhibitors. Neurochem Int. 2011 May;58(6):700-7.
56Rigacci S, Guidotti V, Bucciantini M, et al. Abeta(1-42) aggregates into non-toxic amyloid assemblies in the presence of the natural polyphenol oleuropein aglycon. Curr Alzheimer Res. 2011 Dec;8(8):841-52.
57Flemmig J, Kuchta K, Arnhold J, Rauwald HW. Olea europaea leaf (Ph.Eur.) extract as well as several of its isolated phenolics inhibit the gout-related enzyme xanthine oxidase. Phytomedicine.2011 May 15;18(7):561-6.
58Impellizzeri D, Esposito E, Mazzon E, et al. Oleuropein aglycone, an olive oil compound, ameliorates development of arthritis caused by injection of collagen type II in mice. J Pharmacol Exp Ther.2011 Dec;339(3):859-69.
59Gong D, Geng C, Jiang L, Wang L, Yoshimura H, Zhong L. Mechanisms of olive leaf extract-ameliorated rat arthritis caused by kaolin and carrageenan. Phytother Res. 2012 Mar;26(3):397-402.
60Olive leaf. Monograph. Altern Med Rev. 2009 Mar;14(1):62-6.
Previously, oleuropein was reported to have an anti-hyperglycemic effect in diabetic rats . Oleuropein inhibits hyperglycemia and oxidative stress induced by diabetes, which suggests that administration of oleuropein is helpful in the prevention of diabetic complications associated with oxidative stress .
 Gonzalez M, Zarzuelo A, Gamez MJ, Utrilla MP, Jimenez J, Osuna I. Hypoglycemic activity of olive leaf. Planta Med. 1992;58:513–515. doi:10.1055/s-2006-961538. [PubMed]
 Al-Azzawie HF, Alhamdani MS. Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits. Life Sci. 2006;78:1371–1377. doi:10.1016/j.lfs.2005.07.029. [PubMed
The polyphenol specificity with olive products is not surprising since many Plants (including vine wine plant) in the Mediterranean have developed high levels of polyphenols as a protection mechanism against environmental stressors. ( ) Some of these compounds display antioxidant properties in vitro ( )
^ Vivioli, F., Bellomo, G. &Galli, C. (1998). Free radical-scavenging properties of olive oil polyphenols. Biochemical and Biophysical Research Communications, 247:60-64
^ Wojcikowksi, K., Stevenson, L., Leach, D., Wohlmuth, H., Gobe, G. (2007). Antioxidant capacity of 55 medicinal herbs traditionally used to treat the urinary system: A comparison using a sequential three-solvent extraction process. The Journal of Alternative and Complementary Medicine, 12(1): 103-109.
Does the processing of olives remove oleuropein ?
Phenolic compounds from virgin olive oil have been demonstrated to be highly bioavailable. Vissers et al. found that absorption of administered ligistroside-aglycone, hydroxytyrosol, tyrosol and oleuropein-aglycone was 55–60% in human subjects .
 Vissers MN, Zock PL, Roodenburg AJC, Leenen R, Katan MB. Olive oil phenols are absorbed in humans. J Nutr. 2002;132:409–417. PMid:11880564. [PubMed]
This discovery could help improve understanding of the scientific basis of olive’s health benefits and develop new, low-cost nutraceutical and culinary strategies to fight type 2 diabetes, obesity and related diseases, including even slowing down aging.
As we know, the “doyenne” of Optimal Longevity, Jeanne Calment from the French Mediterranean area, not only relished olives and olive oil, but she also used it topically for her skin and hair. Up to 121 years old, she was free of major old age diseases and peacefully passed a 122 and a half with all of her Consciousness. (See Optimal Longevity Blog).
What is interesting about this olive compound discovery is that it corroborates it role in helping the body to secrete insulin, which is one of the key regulators of glucose metabolism. It’s also been recognized that insulin plays a central role in health of brain cells. Selectively increasing insulin is good for the brain because it helps to control blood sugar and excess blood sugar in the brain. Too much sugar in the brain is quite inflammatory. Azheimers Disease for example is called Type 3 Diabetes. It’s well known that diabetes increases the risk for dementia of all types.
Be that as it may, more studies olives are warrant because there are still mysteries as to why olives (both the fruit and its leaves) activate so many health pathways, from diabetes, dementia to cancer and heart diseases. In effect, there are hundreds of interesting compounds in olives, all of which act in synergy, including with the other foods in the Mediterranean diet.
The Mediterranean diet reduces your risk for virtually every condition associated with aging. Olive oil is a major component of that diet. Olive leaves contain higher amounts of oleuropein, a polyphenol with unique health-improving attributes. These extracts have been used in traditional medicine for centuries to improve age-related diseases.
Now, scientific evidence has shown that these extracts have a remarkable impact on blood pressure and heart disease—and they can help protect against other age-related chronic conditions as well. Convincing evidence now shows that oleuropein-rich olive leaf extracts help prevent many of the underlying factors leading to diabetes, cancer, neurodegenerative diseases, stroke, and arthritis.
Extra-virgin olive oil and olive leaf extract should be considered an important component of one’s health and longevity program.
This discovery reinforces the Institute’s culninary Mediterranean Strategies. But because olive oil is nonetheless partially processed (extracted), it’s important to get best quality (organic extra virgin oil) and to take it with organic ripe olives and a Mediterranean like meal.
Christian Joubert CSO & HMI Director
Source: Creative Commons Attribution-Share Alike 3.0
(1). Ling Wu, Paul Velander, Dongmin Liu, Bin Xu. Olive component oleuropein promotes β-cell insulin secretion and protects β-cells from amylin amyloid induced cytotoxicity. Biochemistry, 2017
(2). Bendini, A; Cerretani, L; Carrasco-Pancorbo, A; Gómez-Caravaca, A. M.; Segura-Carretero, A; Fernández-Gutiérrez, A; Lercker, G (2007). “Phenolic molecules in virgin olive oils: A survey of their sensory properties, health effects, antioxidant activity and analytical methods. An overview of the last decade”. Molecules (Basel, Switzerland). 12 (8): 1679–719.
(3). G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When they are bound to GTP, they are ‘on’, and, when they are bound to GDP, they are ‘off’. G proteins belong to the larger group of enzymes called GTPases.
(4). Prossnitz, Eric R.; Barton, Matthias (2014). “Estrogen biology: New insights into GPER function and clinical opportunities”. Molecular and Cellular Endocrinology. 389 (1–2): 71–83. ISSN 0303-7207. PMC . PMID 24530924. doi:10.1016/j.mce.2014.02.00 n the field of molecular biology,
nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules. In response, these receptors work with other proteins to regulate the expression of specific genes, thereby controlling the development, homeostasis, and metabolism of the organism
(5). Taamalli, A; Arráez-Román, D; Zarrouk, M; Valverde, J; Segura-Carretero, A; Fernández-Gutiérrez, A (2012). “The occurrence and bioactivity of polyphenols in Tunisian olive products and by-products: A review”. Journal of Food Science. 77 (4): R83–92.
(6). Lockyer S, Rowland I, Spencer JP, Yaqoob P, Stonehouse W (2017). “Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial”. Eur J Nutr. 56 (4): 1421–1432. PMC 5486627 . PMID 26951205. doi:10.1007/s00394-016-1188-y. See also Barbaro, B; Toietta, G; Maggio, R; Arciello, M; Tarocchi, M; Galli, A; Balsano, C (2014). “Effects of the Olive-Derived Polyphenol Oleuropein on Human Health”. International Journal of Molecular Sciences. 15 (10): 18508–18524. PMC 4227229 . doi:10.3390/ijms151018508.
(7). Hydroxytyrosol is a phenylethanoid, a type of phenolic phytochemical with antioxidant properties in vitro. In nature, hydroxytyrosol is found in olive leaf and olive oil, in the form of its elenolic acid ester oleuropein and, especially after degradation, in its plain form. Hydroxytyrosol itself in pure form is a colorless, odorless liquid. The olives, leaves and olive pulp contain large amounts of hydroxytyrosol (compared to olive oil), most of which can be recovered to produce hydroxytyrosol extracts. However, it was found that black olives, such as common canned variety, containing iron(II) gluconatecontained little hydroxytyrosol, as iron salts are catalysts for its oxidation.
Thus, it’s better to use fresh non canned olives. Hydroxytyrosol is mentioned by the scientific committee of the European Food Safety Authority as one of several olive oil polyphenols under preliminary research for the potential to affect blood lipid levels.
(8). See as well
^ Herrero, M; Temirzoda, T. N.; Segura-Carretero, A; Quirantes, R; Plaza, M; Ibañez, E (2011). “New possibilities for the valorization of olive oil by-products”. Journal of Chromatography A. 1218 (42): 7511–20.
(9). Abuznait, AH; Qosa, H; Busnena, BA; El Sayed, KA; Kaddoumi, A (Feb 25, 2013). “Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease: In Vitro and in Vivo Studies.”. ACS Chemical Neuroscience. 4 (6): 973–82. Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are involved in Alzheimer’s diseaseas the main component of the amyloid plaques found in the brains of Alzheimer patients. The peptides derive from the amyloid precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. It is now believed that certain misfolded oligomers (known as “seeds”) can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a prion infection. The oligomers are toxic to nerve cells.The other protein implicated in Alzheimer’s disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold. See Nussbaum JM, Seward ME, Bloom GS (Jan–Feb 2013). “Alzheimer disease: a tale of two prions”. Prion. 7 (1): 14–9. PMC . PMID 22965142. doi:10.4161/pri.22118 As well as: Pulawski W, Ghoshdastider U, Andrisano V, Filipek S (Apr 2012). “Ubiquitous amyloids”. Applied Biochemistry and Biotechnology. 166 (7): 1626–43. PMC . PMID 22350870. doi:10.1007/s12010-012-9
(10). Mihai, Andrei (February 20, 2015). “Olive Oil Compound Kills Cancer Cells Within an Hour”. ZME Science. Retrieved February 22, 2015.
(11). Lavars, Nick (February 19, 2015). “Olive oil ingredient leads cancer cells to their death”. Retrieved February 2015. Check date values in: |access-date= (help)
(12). Khanfar, Mohammad A.; Bardaweel, Sanaa K.; Akl, Mohamed R.; El Sayed, Khalid A. (2015-01-01). “Olive Oil-derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies”. Phytotherapy Research. 29: 1776–1782. ISSN 1099-1573. doi:10.1002/ptr.5434.
(14). “Extra-virgin olive oil mimics painkiller”. Nature Publishing Group. 31 August 2005. See also Beauchamp GK, Keast RS, Morel D, et al. (September 2005). “Phytochemistry: ibuprofen-like activity in extra-virgin olive oil”. Nature. 437(7055): 45–6.
(2). A lye is a metal hydroxide traditionally obtained by leaching ashes (containing largely potassium carbonate or “potash”), or a strong alkali which is highly soluble in water producing caustic basic solutions. “Lye” is commonly an alternative name of sodium hydroxide (NaOH) or historically potassium hydroxide (KOH), though the term “lye” refers to any member of a broad range of metal hydroxides.
- Bendini, A; Cerretani, L; Carrasco-Pancorbo, A; Gómez-Caravaca, A. M.; Segura-Carretero, A; Fernández-Gutiérrez, A; Lercker, G (2007). “Phenolic molecules in virgin olive oils: A survey of their sensory properties, health effects, antioxidant activity and analytical methods. An overview of the last decade”. Molecules (Basel, Switzerland). 12 (8): 1679–719. PMID 17960082. doi:10.3390/12081679.
- Rigacci, S; Stefani, M (2016). “Nutraceutical Properties of Olive Oil Polyphenols. An Itinerary from Cultured Cells through Animal Models to Humans”. International Journal of Molecular Sciences. 17 (6): 843. PMC . doi:10.3390/ijms17060843.
- Z. Charrouf and D. Guillaume (2007). “Phenols and Polyphenols from Argania spinosa”. American Journal of Food Technology. 2 (7): 679–683. doi:10.3923/ajft.2007.679.683.
- “How olives are made”. California Olive Committee. 2017. Retrieved 5 August 2017.
- Prossnitz, Eric R.; Barton, Matthias (2014). “Estrogen biology: New insights into GPER function and clinical opportunities”. Molecular and Cellular Endocrinology. 389 (1–2): 71–83. ISSN 0303-7207. PMC . PMID 24530924. doi:10.1016/j.mce.2014.02.002.
- Taamalli, A; Arráez-Román, D; Zarrouk, M; Valverde, J; Segura-Carretero, A; Fernández-Gutiérrez, A (2012). “The occurrence and bioactivity of polyphenols in Tunisian olive products and by-products: A review”. Journal of Food Science. 77 (4): R83–92. PMID 22352878. doi:10.1111/j.1750-3841.2011.02599.x.