Neuroprotective effects of olive oil and its phenolic compounds on neuroinflammation: a systematic review.

Objectives: Neuroinflammation contributes to the pathogenesis of multiple neurological and neurodegenerative diseases but is also involved in non-degenerative conditions such as aging, sleep disorders, depression, and metabolic dysfunctions. Among dietary factors with potential neuroprotective activity, olive oil and its phenolic compounds have attracted interest for their anti-inflammatory properties. This systematic review aimed to assess the effects of olive oil and its main phenolic compounds on neuroinflammation in preclinical in vivo studies.

Methods: A systematic search was conducted using PubMed, Scopus, and Web of Science to identify controlled in vivo studies evaluating the impact of olive oil or its phenolic compounds on neuroinflammatory markers. Thirty-two studies met the inclusion criteria and were critically analyzed for experimental model, type of intervention, and neuroinflammation-related outcomes.

Results: Olive oil, particularly extra-virgin olive oil (EVOO) rich in phenolic compounds, showed anti-inflammatory effects in several models, although results were inconsistent. In contrast, phenolic compounds such as hydroxytyrosol, oleuropein, oleacein, and oleocanthal more consistently reduced glial activation and pro-inflammatory cytokines across diverse experimental paradigms. Hydroxytyrosol emerged as the most frequently studied and effective compound.

Discussion: The preclinical evidence supports the anti-neuroinflammatory potential of olive oil and its phenolic compounds, though the variability in experimental design, compound characterization, and outcome measures limits translational interpretation. While isolated compounds demonstrated more robust effects than whole oil, high doses and lack of pharmacokinetic data raise questions about clinical relevance. Future research should address these limitations and evaluate the neuroimmune effects of olive oil-derived compounds in human studies.