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Oleocanthal 101: A Scientific Review of the Anti-inflammatory, Anti-cancer, and Neuroprotective Benefits

What is oleocanthal?

Oleocanthal is a natural phenolic compound found in extra-virgin olive oil contributing to its distinctive pungent taste and health-promoting properties. As a bioactive molecule, oleocanthal has gained recognition for its potential role in preventing and managing various diseases, particularly due to its anti-inflammatory, anti-cancer, and neuroprotective effects. 


Which olive oil has the highest concentration of oleocanthal? 

The concentration of oleocanthal in extra-virgin olive oil varies widely due to several factors, including the type of olive cultivar, harvest time, malaxation temperature, milling method, and storage conditions. 

Each of these variables significantly influences the final phenolic profile and, consequently, the health benefits associated with oleocanthal. For instance, studies show that the timing of harvest and malaxation temperature impact oleocanthal levels, with specific temperatures often increasing phenolic content through enhanced enzymatic activity. Other influences include the olive's maturation stage and the method of olive paste extraction which can lead to nearly tenfold differences in oleocanthal concentration across varieties. Oleocanthal concentrations in extra virgin olive oil have been shown to range from less than 100 mg/kg for most olive oil varieties, up to over 1000 mg/kg in rare occasions.

 

What are the health benefits of olive oil? 

Oleocanthal Benefits in Combating Inflammation

Oleocanthal acts as a natural anti-inflammatory agent by inhibiting the activity of cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. These enzymes are critical in the synthesis of pro-inflammatory prostaglandins, and their inhibition mimics the effect of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen. By disrupting these pathways, oleocanthal reduces inflammation without some of the side effects associated with synthetic NSAIDs.

 A study published in Antioxidants Journal in 2021 assessed oleocanthal’s effect on inflammation in mice with induced inflammatory responses. In this experiment, mice were administered 10 mg/kg of purified oleocanthal, which led to a significant reduction in pro-inflammatory cytokines, such as IL-1β and TNF-α. The study concluded that oleocanthal could downregulate these cytokines and modulate inflammation in a dose-dependent manner.

A 2017 clinical trial conducted by Agrawal et al. demonstrated the importance of oleocanthal’s concentration in olive oil. In this randomized crossover trial, participants consumed different types of EVOO with varying oleocanthal and phenolic content. 

Results showed that oleocanthal-rich EVOO significantly reduced collagen-stimulated platelet aggregation in healthy men, correlating with oleocanthal content rather than total phenolic content. This suggests that oleocanthal may have distinct anti-inflammatory and cardiovascular benefits by inhibiting platelet activation, separate from other olive oil phenolics. 

These anti-inflammatory properties suggest that oleocanthal could be beneficial in managing chronic inflammatory conditions, such as arthritis, cardiovascular disease, and inflammatory bowel diseases.


Oleocanthal Anti-cancer Benefits

It is well established that consumption of olive oil is correlated with lower cancer rates and mortality.  However, over the last few years, more and more studies directly link oleocanthal to olive oil’s cancer protective activity.

Research suggests that oleocanthal exerts anti-cancer effects through multiple pathways, including the induction of apoptosis, inhibition of cancer cell proliferation, lysosomal membrane permeabilization, and reduction of tumor invasiveness. Oleocanthal has been tested on various cancer types, including breast, prostate, colon, liver, lung, melanoma and more, demonstrating a broad spectrum of activity against malignant cells.

One common mechanism by which cancer cells proliferate is by evading the process of Apoptosis – or programmed cell death. Common anti-cancer agents, in turn, are effective by forcing cancer cells to go through that process.  Experimental evidence suggests that oleocanthal indeed induces apoptosis in many different cancer cell types, essentially forcing cancer cells to “self-destruct.” 

For example, in breast and prostate cancer cell lines oleocanthal shows a strong pro-apoptotic activity, by inhibiting the C-Met Pro-cancerous pathway, indicating it effectively stunts cancer cell growth. 

Another pathway that encourages cancer cell proliferation is referred to as the STAT-3 pathway. Indeed, in several separate experiments, oleocanthal was able to block that pathway and by doing so, increase apoptosis of cancel cells, and shrink tumors both in hepatocellular carcinoma and melanoma models.

Angiogenesis (the generation of blood vessels) is crucial for cancer progression, as it supplies tumors with blood, aiding their growth and metastasis. Marrero et al. explored the potential of oleocanthal in targeting angiogenesis. This study examines the anti-angiogenic properties of oleocanthal and oleacein. Both compounds disrupt angiogenesis—a process crucial to cancer growth—by impairing endothelial cell functions like migration, proliferation, and tube formation.  Mechanistically, these phenols inhibit pathways like PI3K/AKT and MAPK/ERK, suggesting their therapeutic potential as angiogenesis inhibitors in cancer and related diseases.

Since different olive oils have different concentrations of oleocanthal, researchers at Hunter University, in a paper co-authored by kyoord founder Dr. Goren, have looked at the cancer killing abilities of various olive oils, and correlated them to the amount of oleocanthal the oil contained. The authors concluded that olive oils with higher concentration of oleocanthal, were more efficient in killing cancer cells of both prostate and breast cancer, while sparing non-cancerous cells.


Oleocanthal and Neuroprotective Benefits

Oleocanthal exhibits neuroprotective effects through mechanisms including the inhibition of protein misfolding and amyloid-beta (Aβ) aggregation, modulation of neuroinflammatory pathways, and protection of neuronal cells from oxidative stress. 

Neurodegenerative diseases like Alzheimer's disease are often characterized by the accumulation of misfolded proteins, particularly tau and Aβ, which form neurofibrillary tangles and amyloid plaques, respectively. Oleocanthal has shown potential in countering both of these pathological processes. Li et al. found that oleocanthal, at concentrations from 1 to 100 μM, prevents tau protein from aggregating by locking it into an unfolded state, forming a bond with its lysine residues via Schiff base formation, thus inhibiting tau fibrillization, a key contributor to AD 

This was further corroborated by Monti et al. by showing that oleocanthal modifies tau protein through the same mechanism, preventing its abnormal accumulation in the brain.

A more recent study, published in 2023 looked at the other hallmark of Alzheimer’s Disease – the formation of amyloid beta  plaques (Aβ). The study revealed that oleocanthal could disrupt the formation of Aβ plaques in mouse models of Alzheimer’s disease. The study investigated the effects of oleocanthal on this pathology in 5xFAD mice which are often used to model Alzheimer's disease in humans. Mice were administered oleocanthal at a dose of 0.5 mg/kg daily for three months. The results demonstrated that oleocanthal treatment significantly reduced brain Aβ levels and neuroinflammation by suppressing the nuclear factor-κB (NF-κB) pathway and reducing the activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes. These findings suggest that Oleocanthal may play a protective role against Aβ-related pathology in Alzheimer's disease.

Moreover, oleocanthal reduces neuroinflammation, a common feature in AD. Batarseh et al. showed that oleocanthal, at 5 μM, mitigates Aβ-induced toxicity in neuron and astrocyte cultures by preventing the downregulation of synaptic proteins and reducing inflammation in astrocytes

Oleocanthal also exhibits antioxidant properties, which protect neurons from oxidative stress, a factor in neurodegeneration progression. Giusti et al. found that oleocanthal at 10 μM reduced reactive oxygen species levels and increased glutathione in neuron-like cells, improving cell survival under oxidative conditions.

Together, these findings suggest that oleocanthal has significant neuroprotective potential by preventing tau and Aβ aggregation, reducing inflammation, and enhancing Aβ clearance, making it a promising candidate for neurodegeneration treatment and prevention. However, further studies are necessary to fully understand its effects and confirm its benefits in human subjects.


Oleocanthal: What you need to know

Oleocanthal, a unique compound in extra virgin olive oil, offers impressive health benefits, including anti-inflammatory, anti-cancer, and neuroprotective effects. It mimics certain pharmaceutical actions while providing broader protection without common side effects. Regular consumption of high-oleocanthal EVOO could aid in reducing chronic inflammation, preventing certain cancers, and protecting against neurodegenerative diseases like Alzheimer’s. While current findings are promising, further human studies are needed to fully understand its effects and establish optimal intake. Incorporating high-phenolic olive oil into a daily diet may thus support health and disease prevention.


FAQ

Which olive oil has the most oleocanthal?

Greek olive oils, especially those sourced by kyoord are celebrated for their higher than average oleocanthal content. Currently, our kyoord extremely high-phenolic olive oil is the olive oil with the highest oleocanthal concentration, followed by The Governor Limited Edition. These olive oils have 5 to 15 times higher oleocanthal concentration than an average extra virgin olive oil. 


How to tell if an olive oil has oleocanthal?

Your best bet is to check a certificate of analysis from a 3rd party lab listing the amount of oleocanthal in the oil. Since oleocanthal levels can change from year to year, make sure the certificate you are looking at is an updated one that corresponds to the same harvest year for which you are shopping. You can also taste oleocanthal in olive oil: oleocanthal is bitter and a bit pungent. It causes a distinctive stinging sensation at the back of the throat and often elicits an avoidable cough when swallowing the olive oil (we call it the cough of truth!)


Which foods contain oleocanthal?

Oleocanthal is found exclusively in extra virgin olive oil; it is not naturally present in any other foods.


Which olive oil has the most polyphenols? 

High-phenolic olive oils are the best choice for maximum polyphenol content. These specially crafted extra virgin olive oils are produced to ensure a high concentration of health-boosting polyphenols. To identify the highest-quality options, look for third-party certifications that verify polyphenol and oleocanthal levels. This ensures that the olive oil you select is genuinely rich in polyphenols, providing enhanced health benefits.

What are the main oleocanthal benefits? 

Oleocanthal, a unique polyphenol found exclusively in extra virgin olive oil, has been widely studied for its impressive health benefits. Key oleocanthal benefits include its potent anti-inflammatory, anti-cancer, and neuroprotective properties. Research indicates that consuming 1-2 tablespoons daily of high-oleocanthal olive oil can help maximize these health advantages. 

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