Search Results (781)

Background/Objectives: The health-protective properties of olive oil phenolics, including their potential chemopreventive and anticancer effects, have attracted considerable scientific interest. However, their in vivo efficacy and mechanisms of action remain insufficiently understood. Recent advances in extraction and purification technologies have enabled large-scale production of highly purified olive oil phenols and phenolic-rich extracts, facilitating translational research. Methods: Herein, the antitumor efficacy of isolated olive oil phenols and phenolic-rich formulations was investigated in an MDA-MB-231 triple-negative breast cancer (TNBC) xenograft model. Results: Intraperitoneal administration of oleocanthal (OLC), oleuropein aglycone (OleA) or their combination reduced endpoint tumor burden, with OLC exhibiting the most pronounced effect. Oral administration of total olive oil phenolics (OOPs) achieved comparable efficacy. Pre-treatment initiated before tumor cell implantation conferred the greatest protection, consistent with a prophylactic mode of action. In contrast, delayed intervention displayed diminished or no antitumor benefit. Phenolic-rich extra virgin olive oil likewise showed an inhibition trend in tumor progression. Mechanistically, OOPs attenuated plasma protein oxidation, modulated proteasome mediated proteolysis, and reduced γH2AX levels in vivo. Furthermore, OOPs negatively affected the MDA-MB-231 cell migration in a concentration-dependent manner in vitro. Conclusions: Collectively, these findings are consistent with antitumor activities of olive oil phenolics via multiple mechanisms and support their further investigation as prophylactic agents in TNBC and as nutraceuticals. Full article

Extra virgin olive oil (EVOO) is a hallmark of the Mediterranean diet and an important dietary source of bioactive phenolic compounds, including hydroxytyrosol and tyrosol derivatives, which have been investigated in relation to cardiometabolic health. However, the potential metabolic effects of phenolic-rich EVOO in young healthy adults remain poorly characterized. In this randomized crossover trial, 28 healthy adults (29.0 ± 3.4 years) consumed either phenolic-rich EVOO or regular olive oil (OO) (0.7 g/kg/day) for 4 weeks. The cardiometabolic outcomes reported here were secondary endpoints of the trial. Anthropometric measurements, cardiometabolic biomarkers, and urinary phenolic metabolites were assessed at baseline and after each intervention period; selected phenolic metabolites were quantified in 24-h urine using targeted LC–HRMS. Treatment effects were evaluated using mixed-effects models. Compared with OO, EVOO markedly increased urinary hydroxytyrosol-glucuronide (GMR = 9.9; 95% CI: 2.0, 49.0; p = 0.005), together with other hydroxytyrosol- and tyrosol-derived metabolites, providing objective evidence of greater phenolic exposure during the EVOO intervention. Exploratory between-intervention differences favored EVOO for waist circumference (β = −2.21 cm; 95% CI: −3.37, −1.05), waist-related indices, and HbA1c (β = −0.13%; 95% CI: −0.25, −0.01). In exploratory analyses, increases in urinary hydroxytyrosol-glucuronide during EVOO intake were inversely correlated with changes in HbA1c (Spearman’s rho = −0.49, p = 0.011) and WHR (rho = −0.38, p = 0.048). Post hoc sensitivity analyses showed greater stability for the waist-circumference estimate than for HbA1c. Overall, phenolic-rich ‘Corbella’ EVOO substantially increased urinary phenolic metabolite exposure, whereas the observed cardiometabolic differences should be considered exploratory and hypothesis-generating and require confirmation in larger trials specifically powered for these outcomes. Full article

Background/Objectives: Colorectal cancer (CRC) is the second most common cancer-causing death in the United States. The Mediterranean diet, rich in extra-virgin olive oil (EVOO), is associated with a lower risk of colorectal cancer (CRC). Earlier studies reported S-(−)-oleocanthal (OC), the major EVOO phenolic, to be effective in CRC progression and recurrence suppression in a subcutaneous xenograft model by targeting the SMYD2–EZH2/c-MET signaling axis and favorably modulating gut microbiota (GM). However, lead validation in an orthotopically xenografted model that mimics the tumor microenvironment is yet to be achieved. The GM contribution to OC anti-CRC activity remains unknown. Methods: We used an orthotopic intra-cecally xenografted nude mouse model to validate OC anti-KRAS-mutant CRC activity and assessed the contribution of OC GM modulation to this activity using an oral antibiotic depletion strategy. Results: Daily oral 10 mg/kg OC impressively suppressed KRAS^G13D-mutant CRC HCT-116-Luc progression and metastasis more effectively than intraperitoneal administration 3×/week. By contrast, GM depletion with a broad-spectrum antibiotics cocktail (ABC) partially attenuated this activity, suggesting GM contribution to OC anti-CRC activity. Thus, fecal microbiota transplantation (FMT) was conducted using fresh daily oral fecal GM treatments collected from 20 mg/kg OC-dosed nude mouse donors. A week before FMT dosing, orthotopic HCT-116-Luc tumor-bearing recipient mice were subjected to GM depletion using daily oral ABC dosing. Recipient mice treated with FMT from OC-treated donors exhibited dramatic >99% reductions in primary and near-complete suppression of multi-organ metastatic tumor burden versus FMT controls. Conclusions: Collectively, oral OC is validated as an effective anti-KRAS^G13D-mutant CRC lead. Future clinical trials can validate its anti-CRC potential in a human model. Full article

Virgin olive oil (VOO) extraction requires technologies that maximize yield while preserving bioactive compounds and sensory quality. Pulsed electric field (PEF) pretreatment enhances cell membrane permeabilization, facilitating oil release, yet its interaction with malaxation time remains underexplored. This study investigated the synergistic effects of PEF intensity (Low, Mid, High) and malaxation time (15, 30, 60 min at 25 °C) on extraction yield and quality parameters of ‘Picual’ and ‘Arbequina’ virgin olive oils. PEF was applied to olive paste before malaxation. Extraction yield, quality indices (acidity, peroxides, K₂₃₂, K₂₇₀), phenolic content, pigments (chlorophylls, carotenoids), and volatile organic compounds were analyzed. Sensory evaluation was performed by trained panels. Results: Mid-intensity PEF reduced pomace oil content by 33–35% in ‘Picual’ at 30 min malaxation, while ‘Arbequina’ showed limited yield improvements. All oils maintained extra virgin quality standards. PEF increased phenolic content up to 53% in ‘Arbequina’ (Low-intensity, 15–30 min). Pigment concentrations increased with PEF and malaxation duration. LOX-derived volatiles exhibited cultivar-specific responses: Low-intensity PEF reduced C6 aldehydes in ‘Picual’ but enhanced C6 esters (+58%) in ‘Arbequina’. PEF pretreatment optimizes VOO extraction in a cultivar-dependent manner, improving phenolic retention and modulating aroma profiles without compromising extra virgin classification. Full article

Background/Objectives: Extra virgin olive oil (EVOO), a key component of the Mediterranean diet, has attracted research interest because olive-derived phenolics demonstrate potential anticancer activity in experimental models. This review summarizes evidence concerning whole EVOO, phenolic-enriched EVOO, olive phenolic extracts, and the isolated compounds hydroxytyrosol, oleuropein, oleocanthal, and oleacein. Methods: A structured narrative search of PubMed, Web of Science, ScienceDirect, and Google Scholar was conducted for literature published between 2015 and 2025. Evidence was reviewed for breast, prostate, colorectal, pancreatic, bone, oral, liver, gastric, hematological, and brain cancers. Comparatively limited evidence concerning cervical, endometrial, ovarian, melanoma, non-melanoma skin, and thyroid cancers was summarized separately. Results: The molecular evidence was derived primarily from cell culture and animal studies using isolated phenolics and concentrated extracts. Preclinical studies indicate that EVOO phenolics may demonstrate anticancer activity through multiple mechanisms, including antioxidant activity, anti-inflammatory effects, cell cycle arrest, induction of apoptosis, inhibition of metastasis, anti-angiogenic activity, and modulation of key signaling pathways, such as PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Wnt/β-catenin, p53, and epithelial–mesenchymal transition-related pathways. Most molecular and pathway-level evidence was obtained using isolated phenolic compounds in cell culture or animal models, whereas evidence directly examining whole EVOO consumption was largely observational and substantially more limited. Experimental studies also reported that oleocanthal induced lysosomal membrane permeabilization, whereas hydroxytyrosol and oleuropein promoted mitochondria-mediated apoptosis. Furthermore, preclinical combination studies suggested enhanced tumor-cell sensitivity to selected chemotherapeutic, targeted, and immunotherapeutic agents. However, these effects have not been established in patients. Human evidence remains limited mainly to observational dietary associations and small exploratory interventions, with no conclusive demonstration of cancer prevention or therapeutic efficacy. Conclusions: Isolated EVOO-derived phenolic compounds demonstrated promising anticancer mechanisms in preclinical models. However, these results should not be directly extrapolated to dietary EVOO because experimentally administered doses, bioavailability, metabolism, and food-matrix interactions differ substantially from human dietary exposure. Therefore, well-designed studies using chemically characterized EVOO, pharmacokinetic investigations, and controlled human trials are required before dietary or clinical recommendations can be made. Full article

Following the 2021 Montiferru wildfire, one of the largest wildfire events in modern Italian history, assessing the suitability of olive-growing environments for high-quality extra virgin olive oil (EVOO) production is crucial for supporting sustainable agricultural restoration. This study models the spatial distribution and temporal stability of total polyphenol concentration in EVOO (cv. Bosana) across a complex Mediterranean landscape. Olive samples from georeferenced sites were collected during the 2022 (22 samples) and 2023 (37 samples) harvest seasons and processed using a standardized protocol. Spatial modeling was performed via Empirical Bayesian Kriging Regression Prediction (EBKRP), integrating seven bioclimatic and topographic covariates. Cross-validation demonstrated high predictive accuracy with negligible bias (RMSE = 53.3 and 58.8 mg kg⁻¹ for 2022 and 2023, respectively). While single-predictor correlations were weak, multi-variable analysis highlighted a strong interaction between topography and water balance driving phenolic accumulation. The mean prediction map identified regional hotspots approaching600 mg kg⁻¹ of polyphenols content in the obtained olive oils. Spatial overlay analysis successfully delineated “Stable High-Phenolic Core Areas” (>500 mg kg⁻¹ with interannual variation < 100 mg kg⁻¹), filtering out high-altitude marginal zones. This geostatistical approach provides a valuable territorial decision-making tool to support post-fire agricultural reconversion and the valorization of high-quality monovarietal EVOO terroirs. Full article

Optimal harvesting time is crucial for the quality and yield of extra virgin olive oil. Despite the widespread use of visual ripeness, maturity index, and pulp hardness, no study has compared their predictive ability for the quality and production parameters of extra virgin olive oil at industrial scale, thus motivating this work. Fifteen 300 kg olive samples (five replicates per harvesting date) were collected on 11 October, 29 October, and 25 November 2024 and processed within six hours at an industrial olive oil mill. One-way analysis of variance and Multiple Ordinary Least Squares regression were applied to evaluate harvest maturity indicators against primary quality, phenolic profile, yield, temperature, and sensory parameters. The former confirmed a significant main effect of harvesting time for most parameters, while the latter showed that visual ripeness systematically outperformed the maturity index and pulp hardness in seven out of eight models; pulp hardness was the sole exception, proving the strongest correlation with final oil temperature. These findings confirm that visual ripeness—a cost-free, immediately applicable parameter—seems to be the most strongly correlated indicator of the quality, phenolic content, and sensory attributes of extra virgin olive oil, while pulp hardness emerges as an innovative operative tool for optimizing temperature management in the production of extra virgin olive oil. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is driven by complex metabolic and inflammatory disturbances. Extra virgin olive oil (EVOO), a hallmark of the Mediterranean diet, contains numerous bioactive compounds that may exert beneficial effects on liver and cardiometabolic health. This preliminary study investigated the interactions of selected EVOO-derived compounds, with molecular targets implicated in MASLD using an integrated in silico approach. Methods: Phenolic compounds, secoiridoids, fatty acids, sterols, squalene, and vitamin E were evaluated. Physicochemical properties, drug-likeness, and pharmacokinetic profiles were predicted using ADMETlab 3.0. Molecular docking analyses were performed against liver X receptors (LXRα and LXRβ), peroxisome proliferator-activated receptors (PPARα and PPARγ), hydroxymethylglutaryl-CoA reductase, cyclooxygenase-1, and cyclooxygenase-2. Binding modes were further examined by three-dimensional interaction analyses. Results: The investigated compounds displayed heterogeneous physicochemical and pharmacokinetic profiles. Oleuropein, oleacein, and oleocanthal demonstrated the most consistent binding patterns across targets involved in lipid metabolism, inflammation, and cardiometabolic regulation. In contrast, highly lipophilic compounds, including squalene, β-sitosterol, and vitamin E, frequently achieved high docking scores but formed fewer biologically relevant interactions. Conclusions: EVOO phenolics, particularly oleuropein, oleacein, and oleocanthal, emerged as promising multi-target modulators of MASLD-related pathways, supporting the potential role of EVOO in MASLD prevention and management. Full article

Olive oil, particularly virgin (VOO) and extra-virgin olive oil (EVOO), is a central component of the Mediterranean diet and has been associated with cardiometabolic, anti-inflammatory, and intestinal health benefits. Increasing evidence suggests that these effects may involve interactions with the gut microbiota, intestinal barrier, and host inflammatory pathways. This narrative review summarizes current evidence on the impact of olive oil, olive-derived phenolics, and olive oil-rich dietary patterns on gut microbiota modulation, barrier function, inflammatory bowel diseases, and related systemic outcomes. The available literature indicates that olive oil may interact with the gut ecosystem through both its oleic acid-rich lipid matrix and its minor phenolic fraction. VOO and EVOO appear more consistently associated than refined oils with microbial or microbial metabolite profiles related to saccharolytic metabolism, short-chain fatty acid production, mucus-layer dynamics, and anti-inflammatory intestinal environments. Olive-derived phenolics, including hydroxytyrosol, tyrosol, oleuropein derivatives, and oleocanthal, can undergo microbial biotransformation and may influence bile acid metabolism, epithelial barrier integrity, and inflammatory signaling. Whole EVOO evidence is strongest in experimental colitis models, whereas human evidence mainly supports effects on postprandial endotoxemia, lipid oxidation, and selected inflammatory markers. However, findings remain heterogeneous and depend on oil quality, phenolic composition, comparator fat, dietary context, and host condition. Well-controlled human studies directly comparing EVOO, VOO, refined olive oil, and oleic acid-rich controls are needed to clarify reproducible microbiota-mediated effects and their relevance to intestinal and systemic health. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by impaired glucose metabolism, mitochondrial dysfunction, inflammation, oxidative stress, and progressive cognitive decline. Because currently available pharmacological therapies provide only modest symptomatic benefit, nutrition-based interventions are increasingly being explored as complementary strategies for supporting brain metabolism and cognitive resilience. The KetoFLEX 12/3 dietary pattern, developed within the ReCODE (Reversal of Cognitive Decline) program, is a plant-rich, mildly ketogenic nutrition and lifestyle framework that integrates low-glycemic nutrition, time-restricted eating, and personalized metabolic optimization. The diet emphasizes deeply pigmented non-starchy vegetables, extra-virgin olive oil, nuts and seeds, omega-3-rich seafood, and minimally processed foods while limiting refined carbohydrates, sugars, processed foods, and selected grains and dairy products. Emerging mechanistic and clinical evidence suggests that KetoFLEX 12/3 may influence several pathways relevant to AD pathophysiology, including insulin signaling, mitochondrial bioenergetics, neuroinflammation, oxidative stress, autophagy, detoxification pathways, and gut–brain axis function. Observational findings from ReCODE-related studies have reported improvements in metabolic parameters, mood-related outcomes, cognitive measures, and brain volumetrics in participants adhering to multimodal precision-medicine interventions incorporating the KetoFLEX principles. Compared with traditional dietary models such as the Mediterranean or MIND diets, KetoFLEX 12/3 places greater emphasis on mild nutritional ketosis, meal timing, and metabolic personalization based on factors such as ApoE genotype and insulin sensitivity. The objective of this Perspective is to examine the mechanistic rationale, emerging evidence, limitations, and future research priorities for KetoFLEX 12/3 as a precision-nutrition framework for cognitive health in AD. Although much of the current evidence remains mechanistic, observational, or derived from multimodal intervention studies, the framework offers a biologically plausible precision-nutrition model that may inform future research and clinical investigation in cognitive decline. Full article

Exercise-induced reactive oxygen and nitrogen species (RONS) serve as crucial signaling molecules for training adaptation, mitochondrial biogenesis, and inflammatory resolution, rather than being mere markers of oxidative damage. Chronic or excessive high-dose antioxidant supplementation may suppress these vital redox-sensitive pathways. Consequently, this narrative review examines food-based antioxidant strategies as approaches for redox modulation, meaning support for recovery and redox homeostasis without indiscriminately suppressing exercise-induced redox signals that may contribute to training adaptation, while emphasizing the distinction between whole-food matrices and isolated supplements. A structured literature search was conducted across major electronic databases, including PubMed, Web of Science, Scopus, and SPORTDiscus. The search focused on intersecting themes of exercise physiology, redox biology, and sports nutrition. The reviewed evidence includes short-term human intervention studies, systematic reviews, meta-analyses, and mechanistic studies examining tart cherry, berries, pomegranate, cocoa, green tea, beetroot, extra virgin olive oil, and Mediterranean-style dietary patterns. Overall, the evidence suggests that these food-based strategies may influence recovery-related outcomes through mechanisms extending beyond direct radical scavenging, including inflammatory regulation, vascular function, and gut-derived metabolism; however, the strength and consistency of findings vary by food source, outcome, dose, timing, study population, dietary matrix, and bioavailability. Current literature does not support universal, fixed daily antioxidant use. Food-based strategies appear most appropriate during periods of elevated recovery demands, such as heavy training blocks, congested competition, muscle damage, or environmental stress. Food-based antioxidant nutrition should therefore be interpreted as a conceptual, evidence-informed approach to periodized and context-specific recovery support, rather than as a universal or evidence-graded guideline, because much of the available evidence derives from short-term and heterogeneous intervention studies. These strategies should complement foundational sports nutrition practices (energy availability, macronutrient distribution, hydration, and sleep) when balancing the preservation of long-term training adaptations with the need for acute recovery. Full article

This study investigated the influence of different extraction solvents (ethanol and methanol) on antioxidant and oxidative stress parameters in 55 extra virgin olive oil samples obtained from various producers in the Aegean region of Türkiye. In this context, DPPH radical scavenging activity, total phenolic content (TPC), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were determined in both extracts. Ethanol extracts showed higher TPC and DPPH radical scavenging activity, with mean DPPH values of 24.48% and 15.42% for ethanol and methanol extracts, respectively. Similarly, TOS and OSI values were higher in ethanol extracts, whereas TAS values were higher in methanol extracts. Correlation analysis revealed significant negative relationships between antioxidant parameters (TPC and TAS) and OSI, indicating an inverse association between antioxidant capacity and oxidative stress. Principal component analysis (PCA) demonstrated a distinct separation between antioxidant and oxidant variables. Bland–Altman analysis further confirmed systematic differences between extraction methods. Overall, the findings indicate that the extraction solvent is a critical factor in the determination of antioxidant and oxidative stress parameters in olive oil. Ethanol provides a higher phenolic content and radical scavenging activity, whereas methanol appears more effective in assessing total antioxidant capacity. The variability among samples reflects differences in production, processing, and storage conditions. Full article

The question of verification of food quality has stood before scientists since ancient times, and, nowadays, the advances in science and technology have made it a very challenging task. Laser-induced fluorescence (LIF) spectroscopy has become a very useful instrument for sample characterization. Nevertheless, analysis of complex multi-component spectra is difficult to approach. In recent years, the capabilities of artificial intelligence have attracted a lot of attention, as they open doors to efficient solutions of many problems that otherwise require a lot of time, effort, expenses and often inspiration. In the present work, we use LIF spectra of mixtures of sunflower and extra virgin olive oils with different concentrations and apply neural network (NN) algorithms with the aim of improving the strategies for concentration determination. Two different approaches have been applied and their output has been compared and commented. More specifically, the task of concentration recognition has been targeted as a classification and as a fitting problem. We formulate four diagnostic parameters with biochemical meaning and compare the NN performance when training with raw spectra and with the diagnostic parameters. The correct choice of appropriate diagnostic parameters is of importance from the point of view of biochemical interpretability and analysis, whereas “black box” full-spectra training might be beneficial for end-user applications. Our results show that these methods perform well even with very scarce data and outline preliminary strategies for defining diagnostic criteria. Full article

Cyclopiazonic acid (CPA), a neurotoxin produced by Penicillium and Aspergillus genera, induces oxidative stress and neuronal damage, mechanisms implicated in neurodegenerative diseases. This study investigates the oxidative stress induced by CPA in SH-SY5Y human neuroblastoma cells, focusing on mitochondrial membrane potential, mitochondrial superoxide levels, ROS production, lipid peroxidation and gene expression. Additionally, the cytoprotective effects of extra virgin olive oil (EVOO) extract, along with its major polyphenols oleuropein (OLE) and tyrosol (TYR), were evaluated. CPA exposure increased mitochondrial superoxide levels and lipid peroxidation, reducing mitochondrial membrane potential, although no intracellular ROS generation was observed. Gene expression analysis revealed downregulation of antioxidant defense genes (nrf2, nos2, ho1, cat, keap1, nqo1, gpx1 and gsr), with the strongest repression observed for nos2 (93%), nqo1 (83%) and ho1 (79%) at the highest CPA concentration, consistent with oxidative stress markers. EVOO extract demonstrated protective effects, enhancing cell viability across all CPA assayed concentrations (400–600 nM). Conversely, TYR and OLE exhibited variable and concentration-dependent effects, also showing protection to a lesser extent, while EVOO extract proved to be more effective due to synergistic interactions among its phenolic components. Overall, CPA induces mitochondrial oxidative damage as a key mechanism of neurotoxicity, while EVOO phenolics mitigate this toxicity. Full article

Extra virgin olive oil (EVOO) is prone to oxidative degradation during storage, especially after opening, when exposure to oxygen and light accelerates the depletion of antioxidants and promotes the formation of oxidation products, including hydroperoxides and C₇–C₉ aldehydes associated with rancidity. Packaging materials play a critical role in preserving EVOO quality in real-use conditions. This study comparatively evaluated the effectiveness of three widely used packaging materials: green polyethylene terephthalate (PET), bag-in-box (BB), and chrome-plated tin (CPT) in preserving regulatory, sensory, and health-related qualities of EVOO under simulated household use and storage conditions. Methods: PET, BB, and CPT containers (3 L) were totally filled with the same EVOO and stored at 25 °C under a 12 h light/dark cycle, with 75 mL withdrawn daily for 40 days to mimic consumer use. Every 10 days, regulatory quality indices (free acidity (FA), peroxide value (PV), K₂₃₂, and K₂₇₀), antioxidants, volatile compounds, and sensory attributes were evaluated. Results: Free acidity, K₂₃₂, and K₂₇₀ increased slightly in EVOOs across all containers, while EVOO stored in PET showed a sharp rise in PV, exceeding the legal limit after 30 days. Antioxidant depletion was significantly (p ≤ 0.05) more pronounced in the EVOO stored in PET (44% α-tocopherol and 26% total phenols, respectively) than in BB (1% and 11%) and CPT (5% and 12%). The EVOO stored in PET also showed a reduction in C₅–C₆ aldehydes (−26% and −24% compared to BB and CPT, respectively), alongside an accumulation in C7–C9 aldehydes (+8% and +5%), exhibiting higher loss of C₅–C₆ aldehydes and of C₇–C₉ aldehydes, which is responsible for fruity–green notes and rancid defect, respectively, compared to BB and CPT. Conclusions: Overall, the EVOOs stored in BB, followed by CPT, showed higher oxidative stability than those stored in PET, resulting in prolonged “extra virgin” classification and improved preservation of antioxidant content, volatility profile, and sensory quality during consumer-level storage. Full article