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Olive oil’s secret weapon against Alzheimer’s: phenolic compounds

A review article published within the International Journal of Molecular Sciences provides a comprehensive overview of the efficacy of extra-virgin olive oil and its phenolic compounds in stopping and treating Alzheimer’s disease.

Review: Extra-Virgin Olive Oil in Alzheimer’s Disease: A Comprehensive Review of Cellular, Animal, and Clinical Studies. Image Credit: luigi giordano / Shutterstock


Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterised by cognitive decline, memory impairment, and difficulty performing every day activities. About 60-80% of all dementia cases are related to AD. In the US, AD is the sixth leading explanation for death amongst older adults aged 65 years and above.

Two major neuropathological hallmarks of AD include the buildup of amyloid-beta plaques and the formation of neurofibrillary tangles within the brain. One other pathological feature of AD is increased permeability of the blood-brain barrier, which facilitates the entry of harmful substances and immune cells into the brain, resulting in the induction of neuroinflammation and oxidative stress.

The present AD treatments include therapeutic monoclonal antibodies, acetylcholinesterase inhibitors, and N-methyl-D-aspartate (NMDA) antagonists. Although these medicines effectively reduce symptom worsening and improve overall quality of life, they fail to cure the disease or prevent its progression.

A big pool of evidence highlights the positive impact of the Mediterranean weight loss plan in treating and stopping AD. Extra-virgin olive oil is the principal constituent of the Mediterranean weight loss plan, and it incorporates greater than 100 phenolic compounds, including oleuropein aglycone, oleuropein, oleocanthal, oleacein, tyrosol, and hydroxytyrosol. These compounds are known to scale back the chance of developing mild cognitive impairment and AD. 

Impact of extra-virgin olive oil and its phenolic compounds on AD hallmarks

Extra-virgin olive oil and its phenolic compounds prevent pathological hallmarks of AD through various pathways. They disrupt the aggregation of amyloid-beta peptides, increase their clearance from the brain, and stop neuronal damage and oxidative stress.

These compounds inhibit the hyperphosphorylation of tau proteins, resulting in the cessation of neurofibrillary tangle formation and the preservation of important neuronal transport systems. Moreover, they maintain the integrity of the blood-brain barrier and restrict the transportation of neurotoxic substances within the brain.

Robust anti-inflammatory and antioxidant properties of phenolic compounds play vital roles in stopping neuroinflammation and oxidative stress within the brain, which in turn is mandatory for restricting further worsening of AD-related pathologies.

Preclinical studies investigating extra-virgin olive oil and its phenolic compounds

Several in vitro studies have investigated the antioxidant and neuroprotective properties of extra-virgin olive oil extracts and their therapeutic advantages against AD. In neuroblastoma cells, pretreatment with extra-virgin olive oil extracts has been found to induce the expression of key antioxidant enzymes and subsequently prevent free radical-induced oxidative damage. 

Individual phenolic compounds of extra-virgin olive oil, akin to hydroxytyrosol and oleuropein, have been found to stop translocation of nuclear factor kappa B (NFkB) within the nucleus, resulting in reduced production of pro-inflammatory mediators and prevention of neuroinflammation mediated by microglia. Besides inhibiting pro-inflammatory cytokine production, these compounds increase the production of anti-inflammatory cytokines.

Combination treatment with oleuropein aglycone and hydroxytyrosol in neuroblastoma cells has been found to activate autophagic flux, reduce free radical production, prevent mitochondrial dysregulation, and inhibit cell damage brought on by amyloid-beta plaques.

Several studies have highlighted the efficacy of oleocanthal in reducing AD pathological hallmarks. The compound has been found to extend the clearance of amyloid-beta plaques from the brain across the blood-brain barrier and stimulate their degradation.

Several in vivo studies with AD mouse models have demonstrated the therapeutic advantages of extra-virgin olive oil and its phenolic compounds. The treatment of mice with an extra-virgin olive oil-enriched weight loss plan has improved behavioral performance and synaptic integrity, reduced amyloid-beta accumulation and tau protein phosphorylation, and increased autophagy and amyloid-beta clearance.

Oleuropein-rich olive oil has been found to enhance amyloid-beta-related pathologies, prevent neuroinflammation, enhance non-amyloidogenic pathways and synaptic markers, and improve memory performance in mice.

Treatment of mice with oleocanthal has been found to revive the blood-brain barrier integrity, increase autophagy, prevent neuroinflammation, suppress the RAGE/HMGB1 pathway, restore brain ATP level, mitigate anxiety and sleep disturbance, improve spatial working memory, and extend lifespan.

Clinical studies investigating extra-virgin olive oil and its phenolic compounds

Many human clinical trials have assessed the therapeutic efficacy of extra-virgin olive oil. An Italian study conducted on individuals aged 65 years and above has shown the protective efficacy of dietary monounsaturated fatty acid intake against cognitive decline. A scientific review assessing the connection between the Mediterranean weight loss plan and cognitive impairment has found that higher adherence to the weight loss plan is related to a significantly reduced risk of developing AD.

A study conducted on mild cognitive impairment patients has shown that intake of extra-virgin olive oil for over 12 months is related to increased levels of neuroprotective proteins in serum, which in turn is related to a discount in oxidative stress and inflammation. The additional-virgin olive oil treatment has also been found to modulate AD-related biomarkers within the blood.

One other study on mild cognitive impairment patients revealed that Greek high-phenolic early-harvest extra-virgin olive oil and moderate-phenolic extra-virgin olive oil have higher efficacy in improving cognitive performance than the Mediterranean weight loss plan.

A recent pilot study has shown that intake of extra-virgin olive oil for six months is related to increased brain functional connectivity, improved blood-brain barrier integrity, and improved memory in mild cognitive impairment patients. A major enhancement in cognitive function has also been noticed in older adults consuming extra-virgin olive oil- or nut-supplemented Mediterranean weight loss plan.

In mild AD patients, a mix of oleuropein and S-acetyl glutathione has been found to significantly improve cognitive functions, memory, executive functions, and behavioral disorders.  

Overall, the outcomes of preclinical and clinical studies highlight the protective efficacy of extra-virgin olive oil and its phenolic compounds against AD development and progression.

Journal reference:

  • Alkhalifa AE. 2024. Extra-Virgin Olive Oil in Alzheimer’s Disease: A Comprehensive Review of Cellular, Animal, and Clinical Studies. International Journal of Molecular Sciences. DOI: 10.3390/ijms25031914, https://www.mdpi.com/1422-0067/25/3/1914
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