Effects Of Olive Oil Phenols Research Articles

Effect of olive oil phenols on oxidative stress biomarkers: A systematic review and dose-response meta-analysis of randomized clinical trials.

The phenolic content of olive oil has a role in cardiovascular protection. Some clinical trial studies demonstrated that phenolic compounds of olive oil have antioxidant activity which can protect macronutrients from oxidative damages. The aim of this study was to summarize the results of clinical trials which assessed the effects of high- versus low-phenol olive oil on oxidative stress biomarkers levels. We searched Scopus, PubMed, Web of Science, Google Scholar, ProQuest, and Embase up to July 2021. Eight clinical trials which evaluated the effect of the phenolic content of olive oil on oxidized-LDL (ox-LDL), malondialdehyde (MDA), or ferric-reducing ability of plasma (FRAP) were included the meta analysis. A significant decrease was observed in ox-LDL level (WMD: -0.29 U/L; 95% CI: -0.51, -0.07) and MDA (WMD: -1.82 μmoL/L; 95% CI: -3.13, -0.50). However, after subgroup analysis for MDA, the result was not significant for not serious limitation (SMD: -0.05, 95% CI: -0.35 to 0.24), but significant for serious limitation (SMD: -3.64, 95% CI: -4.29 to -2.99). Also, no significant change was found in FRAP (WMD: 0.0 mmoL/L; 95% CI: -0.03, 0.04) level. Dose-response analysis indicated a significant linear relationship between the phenolic content of olive oil and ox-LDL. The present study showed some beneficial effects of high-phenol compared with low-phenol olive oil on ox-LDL and MDA levels. According to the meta-regression analysis along with the increasing phenolic content of olive oil, a reduction in oxidative stress biomarkers was observed.

The secoiridoid profile of virgin olive oil conditions phenolic metabolism

The European Food Safety Authority highlights the beneficial effects of olive oil phenols, mainly, secoiridoids. Nevertheless, the metabolism of secoiridoids in humans has not been fully elucidated. This research evaluated the metabolism of secoiridoids in humans after intake of olive oils with diverse phenolic profiles. For this purpose, three extra virgin olive oils (EVOOs) were ingested by six volunteers at scheduled meals, and urine samples were collected the following morning for subsequent LC–MS/MS analysis. Using untargeted analysis, urinary metabolites revealed representative patterns associated with the various olive oil phenolic contents in absolute and relative terms. We were able to identify metabolites obtained through phase I, phase II, and microbial metabolism with discrimination between tyrosol and hydroxytyrosol derivatives. Metabolism of phenols is differentially activated as a function of the olive oil secoiridoids content, and this proof-of-concept study shows how urinary metabolites represent olive oil phenolic content.

Natural Molecules for Healthy Lifestyles: Oleocanthal from Extra Virgin Olive Oil.

Extra virgin olive oil (EVOO) is the main source of fat in the Mediterranean diet. Phenolic compounds of EVOO, in particular, secoiridoids, are minor components that have generated special interest due to their positive effects on human health, supported by several clinical trials. This review summarizes the most recent findings on the pharmacological properties and action's mechanisms of secoiridoid oleocanthal, focusing attention on inflammation, oxidative stress, cancer, neurodegenerative processes, and rheumatic diseases. Being of relevance to the clinical effects of EVOO intake, the bioavailability and biotransformation of EVOO polyphenols are addressed. Moreover, this review summarizes the factors that may influence the oleocanthal concentration in EVOO. With the growing incidence of age- and lifestyle-related diseases, the current data indicated that the administration of EVOO rich in secoiridoids may be helpful in the prevention or treatment of different pathologies with an inflammatory component. Although promising, the future raises several questions and challenges, which are discussed here. The real beneficial effects of olive oil phenols on human health need to be clarified in new, well-designed clinical studies.

Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols.

Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the “senescence-associated-secretory-phenotype” (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4–6 weeks) treatment with 1 μM hydroxytyrosol (HT) or 10 μM oleuropein aglycone (OLE) on senescence/inflammation markers. Both phenols were effective in reducing β-galactosidase-positive cell number and p16 protein expression. In addition, senescence/inflammation markers such as IL-6 and metalloprotease secretion, and Ciclooxigenase type 2 (COX-2) and α-smooth-actin levels were reduced by phenol treatments. In NHDF, COX-2 expression, Nuclear Factor κ-light-chain-enhancer of activated B cells (NFκB) protein level and nuclear localization were augmented with culture senescence and decreased by OLE and HT treatment. Furthermore, the inflammatory effect of Tumor Necrosis Factor α (TNFα) exposure was almost completely abolished in OLE- and HT-pre-treated NHDF. Thus, the modulation of the senescence-associated inflammatory phenotype might be an important mechanism underlying the beneficial effects of olive oil phenols.

Anti-cancer properties of olive oil secoiridoid phenols: a systematic review of in vivo studies.

Epidemiological studies suggest that olive oil intake is associated to a reduced risk of cancer. Recently, the chemopreventive activity of olive oil has been attributed to its unique phenolic compounds represented by phenolic alcohols, hydroxytyrosol (3,4-dihydroxyphenylethanol: 3,4-DHPEA) and tyrosol (p-hydroxyphenylethanol: p-HPEA), and their secoiridoid derivatives 3,4-DHPEA-EA (oleuropein aglycon), p-HPEA-EA (ligstroside aglycon), 3,4-DHPEA-EDA, p-HPEA-EDA (oleocanthal), and oleuropein. Several studies have demonstrated that these compounds are able to inhibit proliferation and induce apoptosis in different tumor cell lines. These in vitro effects have been recently summarized in several reviews. The aim of this systematic review was to evaluate the in vivo anti-cancer activities of secoiridoid phenols as evidenced by either animal models of carcinogenesis or human intervention trials. From the literature research through "PubMed" and "Web of Science", 16 animal studies and 5 human intervention trials were identified and included in the review. Most of the animal studies have confirmed the ability of these compounds to inhibit the carcinogenesis process at both initiation and promotion/progression phases. All human intervention trials have investigated the effects of olive oil phenols on DNA damage. Among the five selected studies, three have shown a significant preventive effect on oxidative DNA damage in terms of reduction of 8-oxo-7,8-dihydro-2'-deoxyguanosine in urine, in mitochondria DNA of mononuclear cells and in lymphocyte DNA. The other two studies failed to see an effect on the urinary excretion of either etheno-DNA adducts or oxidation products of guanine. Further investigations are necessary to clarify the real chemopreventive potential of olive oil secoiridoid phenols on humans performing intervention studies on populations at high cancer risk.

Effect of olive oil phenols on the production of inflammatory mediators in freshly isolated human monocytes

Recent in vitro and in vivo studies suggest that the anti-inflammatory properties of extra virgin olive oil may be involved in the prevention of chronic degenerative diseases. In this study, the ability of olive oil phenols to influence the release of superoxide anions (O2−), prostaglandin E2 (PGE2) and tumor necrosis factor α (TNFα) and the expression of cyclooxygenase2 (COX2) in human monocytes, freshly isolated from healthy donors, was investigated. O2− were measured by superoxide dismutase-inhibitable cytochrome c reduction and PGE2 and TNFα production were determined in culture medium with appropriate enzyme immunoassay kits. COX2 mRNA and protein were evaluated by quantitative reverse transcription-polymerase chain reaction and Western immunoblotting, respectively. Treatment of monocytes for 24 h with 100 μM of hydroxytyrosol (3,4-DHPEA), tyrosol (p-HPEA) and their secoiridoid derivatives (3,4-DHPEA and p-HPEA linked to the dialdehydic form of elenolic acid: 3,4-DHPEA-EDA and p-HPEA-EDA, respectively) significantly (P<.05) inhibited the production of O2− as follows: 3,4-DHPEA (40%,), p-HPEA (9%), 3,4-DHPEA-EDA (25%) and p-HPEA-EDA (36%). Hydroxytyrosol also considerably reduced the expression of COX2 at both the mRNA and protein level (P<.05) and caused a clear dose-dependent reduction of PGE2 released into the culture medium (45% and 71% at 50 and 100 μM, respectively, P<.05). The COX2 mRNA was also efficiently inhibited by the secoiridoids. Moreover, it was shown that hydroxytyrosol increased the monocytes TNFα production. In addition to other chemopreventive properties, these results suggest that the health effects of olive oil phenols may be related to their ability to modulate the production of pro-inflammatory molecules, a property common to non-steroidal anti-inflammatory drugs.

Health effects of olive oil polyphenols: Recent advances and possibilities for the use of health claims

The Mediterranean diet and consumption of olive oil have been connected in several studies with longevity and a reduced risk of morbidity and mortality. Lifestyle, such as regular physical activity, a healthy diet, and the existing social cohesion in Southern European countries have been recognised as candidate protective factors that may explain the Mediterranean Paradox. Along with some other characteristics of the Mediterranean diet, the use of olive oil as the main source of fat is common in Southern European countries. The benefits of consuming olive oil have been known since antiquity and were traditionally attributed to its high content in oleic acid. However, it is now well established that these effects must also be attributed to the phenolic fraction of olive oil with its anti-oxidant, anti-inflammatory and anti-microbial activities. The mechanisms of these activities are varied and probably interconnected. For some activities of olive oil phenolic compounds, the evidence is already strong enough to enable the legal use of health claims on foods. This review discusses the health effects of olive oil phenols along with the possibilities of communicating these effects on food labels.

Potential of olive oil phenols as chemopreventive and therapeutic agents against cancer: A review of in vitro studies

Olive oil is a common component of Mediterranean dietary habits. Epidemiological studies have shown how the incidence of various diseases, including certain cancers, is relatively low in the Mediterranean basin compared to that of other European or North America countries. Current knowledge indicates that the phenolic fraction of olive oil has antitumor effects. In addition to the ability to be chemopreventive, with its high antioxidant activity, the antitumor effects of olive oil phenols (OO-phenols) has been studied because of their capacity to inhibit proliferation and promote apoptosis in several tumor cell lines, by diverse mechanisms. This review will summarize and discuss the most recent relevant results on the antitumor effect of OO-phenols on leukemia tumor cells, colorectal carcinoma cells, and breast cancer (BC) cells. In particular, very recent data will be reported and discussed showing the molecular signaling pathways activated by OO-phenols in different histopathological BC cell types, suggesting the potential use of OO-phenols as adjuvant treatment against several subsets of BC. Data summarized here represent a good starting point for more extensive studies for better insight into the molecular mechanisms induced by OO-phenols and to increase the availability of chemopreventive or therapeutic drugs to fight cancer.

Long-Term Dietary Extra-Virgin Olive Oil Rich in Polyphenols Reverses Age-Related Dysfunctions in Motor Coordination and Contextual Memory in Mice: Role of Oxidative Stress

The aim of this study was to evaluate the effects of olive oil phenols on brain aging in mice and to verify whether the antioxidant and antiinflammatory activities of these polyphenols were involved. C57Bl/6J mice were fed from middle age to senescence with extra-virgin olive oil (10% wt/wt dry diet) rich in phenols (total polyphenol dose/day, 6 mg/kg). Behavioral tests were employed to assess cognitive, motor, and emotional behavior after 6 or 12 months of treatment. Parameters of oxidative status and inflammation were measured in different brain areas at the same times and evaluated for correlation with behavioral changes. The treatment with olive oil phenols improved contextual memory in the step-down test to levels similar to young animals and prevented the age-related impairment in motor coordination in the rotarod test. This motor effect was correlated with reduced lipid peroxidation in the cerebellum (p<0.05), whereas the memory effect did not correlate with oxidation or inflammation parameters. In conclusion, this work points out that natural polyphenols contained in extra-virgin olive oil can improve some age-related dysfunctions by differentially affecting different brain areas. Such a modulation can be obtained with an olive oil intake that is normal in the Mediterranean area, provided that the oil has a sufficiently high content of polyphenols.

Inhibition of NF‐ κB Activity by Minor Polar Components of Extra‐Virgin Olive Oil at Gastric Level

The present work evaluates the effect of olive oil phenols on NF-κB activity in human gastric adenocarcinoma cells. The total phenol content was measured by the Folin Ciocalteu method, whereas the composition was assessed by LC-MS/MS analysis. Secoiridoids represented 71% and 83% of the Italian and Spanish extracts, respectively, phenol alcohols were in the range 9-13%. Ligustroside aglycone was the most abundant (37% and 46%, respectively, in the Italian and Spanish sample), and the concentration of flavonoids AP and LU was below 1%. Phenol extracts were assayed at 0.25-7.5 µg/mL, whereas single compounds were at 0.5-25 µM. Both the extracts inhibited the NF-κB driven transcription in a concentration-dependent manner: IC(50) for the Italian and the Spanish extract were 0.86 and 1.28 µg/mL, respectively. The IC(50) for individual compounds ranged from 4.5 to 13 µM. All the compounds under study inhibited nuclear translocation as well. The data suggest that consumption of extra-virgin olive oil may be beneficial for preventing the onset of gastric inflammation leading to more serious diseases.

Beneficial effects of olive oil phenols on the aging process: Experimental evidence and possible mechanisms of action

Human studies indicate that consumption of olive oil is associated with decreased mortality, reduced cardiovascular risk and improved cognitive function in the elderly. Many of these benefits are thought to be due to the phenolic content of olive oil. In support of this, intervention studies in humans indicate that olive oil phenols protect blood lipids from oxidation and improve blood parameters of inflammation, hemostasis and vascular function, all risk factors for cardiovascular disease. The aim of this review is to evaluate the experimental evidence that olive oil phenols are beneficial to the aging process. Animal studies suggest that olive oil phenols have preventive actions on age-related cognitive and motor dysfunction, an important cause of disability in the elderly. Supporting mechanistic in vitro studies indicate that olive oil phenols may inhibit inflammatory pathways and associated proteins, induce pathways related to cell protection and survival, and modulate pathways related to energy metabolism similar to anti-aging substances. Furthermore, they can interact with beta-amyloid peptide and Tau protein to inhibit the formation of protein aggregates, a hallmark of Alzheimer’s disease. However, caution should be expressed in interpreting these in vitro data are as they are based on experiments carried out mainly using un-physiological concentrations of native olive phenols rather than phenolic metabolites. In conclusion, while in vivo data for the beneficial effects of olive oil phenols in aging are growing, a mechanistic explanation for these effects requires much additional research on the effects of metabolites at relevant concentrations.

Oxidative DNA Damage Is Prevented by Extracts of Olive Oil, Hydroxytyrosol, and Other Olive Phenolic Compounds in Human Blood Mononuclear Cells and HL60 Cells

Our aim in this study was to provide further support to the hypothesis that phenolic compounds may play an important role in the anticarcinogenic properties of olive oil. We measured the effect of olive oil phenols on hydrogen peroxide (H2O2)-induced DNA damage in human peripheral blood mononuclear cells (PBMC) and promyelocytic leukemia cells (HL60) using single-cell gel electrophoresis (comet assay). Hydroxytyrosol [3,4-dyhydroxyphenyl-ethanol (3,4-DHPEA)] and a complex mixture of phenols extracted from both virgin olive oil (OO-PE) and olive mill wastewater (WW-PE) reduced the DNA damage at concentrations as low as 1 μmol/L when coincubated in the medium with H2O2 (40 μmol/L). At 10 μmol/L 3,4-DHPEA, the protection was 93% in HL60 and 89% in PBMC. A similar protective activity was also shown by the dialdehydic form of elenoic acid linked to hydroxytyrosol (3,4-DHPEA-EDA) on both kinds of cells. Other purified compounds such as isomer of oleuropein aglycon (3,4-DHPEA-EA), oleuropein, tyrosol, [p-hydroxyphenyl-ethanol (p-HPEA)] the dialdehydic form of elenoic acid linked to tyrosol, caffeic acid, and verbascoside also protected the cells against H2O2-induced DNA damage although with a lower efficacy (range of protection, 25–75%). On the other hand, when tested in a model system in which the oxidative stress was induced by phorbole 12-myristate 13-acetate-activated monocytes, p-HPEA was more effective than 3,4-DHPEA in preventing the oxidative DNA damage. Overall, these results suggest that OO-PE and WW-PE may efficiently prevent the initiation step of carcinogenesis in vivo, because the concentrations effective against the oxidative DNA damage could be easily reached with normal intake of olive oil.

Multiple pharmacological effects of olive oil phenols

Olive oil is a unique component of Mediterranean diet and is likely to be partially responsible for the health effects of this diet. Although the medicinal potential of olive oil has been largely attributed to the antioxidant effects of bio-phenols derived from olive oil, accumulating evidence strongly suggests that, to elucidate olive oil’s benefits to human health, we have to go beyond antioxidants. In this communication, through summarizing the reference-reported and database-recorded pharmacological information of olive oil phenols, we reveal that multiple pharmacological effects, other than antioxidant potential, are involved in olive oil phenols, which is of significance for understanding the health benefits of olive oil in the Mediterranean diet.

Bioavailability and antioxidant effects of olive oil phenols in humans: a review.

We reviewed the bioavailability and antioxidant effects of phenols from extra virgin olive oil. We searched the MEDLINE database for the years 1966-2002. To review the bioavailability of olive oil phenols, we selected animal and human studies that studied the absorption, metabolism, and urinary excretion of olive oil phenols. We also estimated the intake of the various phenols in the Mediterranean area. To review the antioxidant effects of olive oil phenols, we included human and animal studies on the effect of olive oil phenols on markers of oxidative processes in the body. We excluded studies without a proper control treatment and studies in which the antioxidant effects of phenols could not be disentangled from those of the fatty acid composition of olive oil. Bioavailability studies in humans show that the absorption of olive oil phenols is probably larger than 55-66 mol%, and that at least 5% is excreted in urine as tyrosol and hydroxytyrosol. Animal studies suggest that phenol-rich olive oil lowers oxidisability of ex vivo low-density lipoprotein (LDL) particles or lowers markers in urine of oxidative processes in the body. In five out of seven human studies, however, these effects of phenols were not found. There are no data on the phenol concentrations in plasma that are attainable by intake of olive oil. We estimated that 50 g of olive oil per day provides about 2 mg or approximately 13 micromol of hydroxytyrosol-equivalents per day, and that the plasma concentration of olive oil phenols with antioxidant potential resulting from such an intake can be at most 0.06 micromol/l. This is much lower than the minimum concentrations of these phenols (50-100 micromol) required to show antioxidant activity in vitro. Although phenols from olive oil seem to be well absorbed, the content of olive oil phenols with antioxidant potential in the Mediterranean diet is probably too low to produce a measurable effect on LDL oxidisability or other oxidation markers in humans. The available evidence does not suggest that consumption of phenols in the amounts provided by dietary olive oil will protect LDL against oxidative modification to any important extent.