Dilation of Pregnant Rat Uterine Arteries with Phenols from Extra Virgin Olive Oil Is Endothelium-Dependent and Involves Calcium and Potassium Channels.

During pregnancy, uterine vasculature undergoes significant circumferential growth to increase uterine blood flow, vital for the growing feto-placental unit. However, this process is often compromised in conditions like maternal high blood pressure, particularly in preeclampsia (PE), leading to fetal growth impairment. Currently, there is no cure for PE, partly due to the adverse effects of anti-hypertensive drugs on maternal and fetal health. This study aimed to investigate the vasodilator effect of extra virgin olive oil (EVOO) phenols on the reproductive vasculature, potentially benefiting both mother and fetus. Isolated uterine arteries (UAs) from pregnant rats were tested with EVOO phenols in a pressurized myograph. To elucidate the underlying mechanisms, additional experiments were conducted with specific inhibitors: L-NAME/L-NNA (10-4 M) for nitric oxide synthases, ODQ (10-5 M) for guanylate cyclase, Verapamil (10-5 M) for the L-type calcium channel, Ryanodine (10-5 M) + 2-APB (3 × 10-5 M) for ryanodine and the inositol triphosphate receptors, respectively, and Paxilline (10-5 M) for the large-conductance calcium-activated potassium channel. The results indicated that EVOO-phenols activate Ca2+ signaling pathways, generating nitric oxide, inducing vasodilation via cGMP and BKCa2+ signals in smooth muscle cells. This study suggests the potential use of EVOO phenols to prevent utero-placental blood flow restriction, offering a promising avenue for managing PE.

The Effects of Olive Oil Consumption on Biochemical Parameters and Body Mass Index of People with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder, is closely associated with insulin resistance, obesity, and metabolic syndromes. A body of research has proposed that olive oil, a basic component of the Mediterranean diet with antioxidant and anti-inflammatory properties, may alleviate metabolic disturbances and retard the progression of NAFLD. We conducted a systematic review and meta-analysis to assess the effectiveness of olive oil intake in people with NAFLD. We systematically searched the major electronic databases (PubMed/MEDLINE, Scopus, Cochrane Central Register of Controlled Trials), as well as grey literature sources, to identify randomized controlled trials (RCTs) investigating the effects of olive oil consumption on biochemical and anthropometric parameters of individuals with NAFLD. The quality of the studies was evaluated using the risk-of-bias tool 2.0 (RoB 2). The mean difference (MD) and the 95% confidence interval (CI) were calculated using fixed-effects and random-effects models. Seven RCTs involving 515 subjects were included in the analysis. In the random-effects model, no statistically significant differences were identified with respect to alanine transaminase (MD = -1.83 IU/L, 95% CI: -5.85, 2.19 IU/L, p = 0.37, I2 = 69%) and aspartate transaminase (MD = -1.65 IU/L, 95% CI: -4.48, 1.17 IU/L, p = 0.25, I2 = 72%) levels or waist circumference values (MD = -0.23 cm, 95% CI: -1.23, 0.76 cm, p = 0.65, I2 = 0%). However, a significant effect on body mass index was observed (MD = -0.57 kg/m2, 95% CI: -1.08, -0.06 kg/m2, p = 0.03, I2 = 51%) for subjects who received olive oil compared to those who received an alternative diet or placebo. The findings of the present meta-analysis suggest a modestly positive impact of olive oil intake on body weight in people with NAFLD.

In Vitro Antibacterial Activity of Ozonated Olive Oil against Bacteria of Various Antimicrobial Resistance Profiles Isolated from Wounds of Companion Animals.

Frequent colonization and bacterial infection of skin wounds in small animals prevent or impair their healing. However, the broadly applied antimicrobial therapy of wounds is not always necessary and promotes the spread of bacterial resistance. Thus, alternatives to antimicrobial therapy, including preventive measures in the form of wound dressings with antibiotic properties, should be searched for. The aim of this study was to develop a new, efficient, cost-effective and non-toxic formulation with antimicrobial properties to serve as an alternative to antibiotic administration in wound-healing stimulation in companion animals. Nano/microencapsulated ozonated olive oil in a hyaluronan matrix was developed, with ozone concentration high enough to prevent bacterial growth. The presence and size of nano- and microcapsules were determined with scanning electron microscopy (SEM). Antibacterial activity of developed formulations was examined in vitro on 101 Gram-positive and Gram-negative bacteria isolated from the wounds of companion animals. The highest ozone concentration in the developed formulations inhibited the growth of 40.59% bacteria. Species and genus-specific differences in reactions were observed. Enterococcus spp. proved the least susceptible while non-pathogenic Gram-positive bacteria were the most susceptible to the examined formulations. Changes in the bacterial morphology and cell structure of Psychrobacter sanguinis suspension mixed with Ca-stabilized formulations with nano/microencapsulated ozonized olive oil were revealed during SEM observations. The combination of compounds that promote wound healing (hyaluronic acid, olive oil, ozone and calcium) with the antibacterial activity of the developed formula makes it a promising bionanocomposite for use as a topical dressing.

Evaluation of the protective and therapeutic effects of extra virgin olive oil rich in phenol in experimental model of neonatal necrotizing enterocolitis by clinical disease score, inflammation, apoptosis, and oxidative stress markers.

BACKGROUND AND AIM: Necrotizing Enterocolitis (NEC) is an inflammation-associated ischemic necrosis of the intestine. To investigate the effects of extra virgin olive oil (EVOO) on inflammation, oxidative stress, apoptosis, and histological changes in NEC-induced newborn rats. MATERIALS AND METHODS: 24 rats were randomly divided into three groups: control, NEC and NEC + EVOO. NEC induction was performed using hypoxia-hyperoxia, formula feeding, and cold stress. The NEC + EVOO group received 2 ml/kg EVOO with high phenolic content by gavage twice a day for 3 days. 3 cm of bowel including terminal ileum, cecum, and proximal colon was excised. RESULTS: Weight gain and clinical disease scores were significantly higher in the NEC + EVOO group than in the NEC group (p < 0.001). EVOO treatment caused significant decreases in IL1ß, IL6 levels (p = 0.016, p = 0.029 respectively) and EGF, MDA levels (p = 0.032, p = 0.013 respectively) compared to NEC group. Significant decreases were observed in IL6 gene expression in the NEC + EVOO group compared to the NEC group (p = 0.002). In the group NEC + EVOO, the number of Caspase-3 positive cells was found to be significantly reduced (p < 0.001) and histopathological examination revealed minimal changes and significantly lower histopathological scores (p < 0.001). CONCLUSION: Phenol-rich EVOO prevents intestinal damage caused by NEC by inhibiting inflammation, oxidative stress, apoptosis.

Ozonated Olive Oil Intake Attenuates Hepatic Steatosis in Obese db/db Mice.

Chronic inflammation and insulin resistance lead to metabolic syndrome and there is an urgent need to establish effective treatments and prevention methods. Our previous study reported that obese model Zucker (fa/fa) rats fed with ozonated olive oil alleviated fatty liver and liver damage by suppressing inflammatory factors. However, differences among animal species related to the safety and efficacy of ozonated olive oil administration remain unclear. Therefore, this study investigated the effects of oral intake of ozonated olive oil on lipid metabolism in normal mice and mice in the obesity model. C57BL/6J and db/db mice were fed the following AIN-76 diets for four weeks: the mice were either fed a 0.5% olive oil diet (Control diet) or 0.5% ozonated olive oil diet (Oz-Olive diet) in addition to 6.5% corn oil. The results indicated that four weeks of Oz-Olive intake did not adversely affect growth parameters, hepatic lipids or serum parameters in normal C57BL/6J mice. Subsequent treatment of db/db mice with Oz-Olive for four weeks reduced the levels of hepatic triglycerides, serum alkaline phosphatase, and serum insulin. These effects of Oz-Olive administration might be due to suppression of fatty acid synthesis activity and expression of lipogenic genes, as well as suppression of inflammatory gene expression. In conclusion, this study confirmed the safety of Oz-Olive administration in normal mice and its ability to alleviate hepatic steatosis by inhibiting fatty acid synthesis and inflammation in obese mice.

Extra Virgin Olive Oil Phenolic Compounds Modulate the Gene Expression of Biomarkers Involved in Fibroblast Proliferation and Differentiation.

Extra virgin olive oil phenolic compounds have been identified as possible biostimulant agents against different pathological processes, including alterations in healing processes. However, there is little evidence on the molecular mechanisms involved in this process. The aim was to analyse the effect of hydroxytyrosol, tyrosol, and oleocanthal on fibroblast gene expression. PCR was used to determine the expression of different differentiation markers, extracellular matrix elements, and growth factors in cultured human fibroblasts CCD-1064Sk treated with different doses of hydroxytyrosol (10-5 M and 10-6 M), tyrosol (10-5 M and 10-6 M), and oleocanthal (10-6 M and 10-7 M). After 24 h of hydroxytyrosol treatment, increased expression of connective tissue growth factor, fibroblast growth factor (FGF), platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor ß1 (TGF-ß1), and their receptors was observed. Tyrosol and olecanthal modulated the expression of FGF and TGFßR1. All phytochemicals tested modified the expression of differentiation markers and extracellular matrix elements, increasing gene expression of actin, fibronectin, decorin, collagen I, and III. Phenolic compounds present in extra virgin olive could have a beneficial effect on tissue regeneration by modulating fibroblast physiology.

Olive oil nanoemulsion containing curcumin: antimicrobial agent against multidrug-resistant bacteria.

The present work aimed to develop, characterize, and evaluate the antibacterial and antibiofilm activity of two nanoemulsions (NEs) containing 500 µg/mL of curcumin from Curcuma longa (CUR). These NEs, produced with heating, contain olive oil (5%) and the surfactants tween 80 (5%) and span 80 (2.5%), water q.s. 100 mL, and were stable for 120 days. NE-2-CUR presented Ø of 165.40 ± 2.56 nm, PDI of 0.254, ζ of - 33.20 ± 1.35 mV, pH of 6.49, and Entrapment Drug Efficiency (EE) of 99%. The NE-4-CUR showed a Ø of 105.70 ± 4.13 nm, PDI of 0.459, ζ of - 32.10 ± 1.45 mV, pH of 6.40 and EE of 99.29%. Structural characterization was performed using DRX and FTIR, thermal characterization using DSC and TG, and morphological characterization using SEM, suggesting that there is no significant change in the CUR present in the NEs and that they remain stable. The MIC was performed by the broth microdilution method for nine gram-positive and gram-negative bacteria, as well as Klebsiella pneumoniae clinical isolates resistant to antibiotics and biofilm and efflux pump producers. The NEs mostly showed a bacteriostatic profile. The MIC varied between 125 and 250 µg/mL. The most sensitive bacteria were Staphylococcus aureus and Enterococcus faecalis, for which NE-2-CUR showed a MIC of 125 µg/mL. The NEs and ceftazidime (CAZ) interaction was also evaluated against the K. pneumoniae resistant clinical isolates using the Checkerboard method. NE-2-CUR and NE-4-CUR showed a synergistic or additive profile; there was a reduction in CAZ MICs between 256 times (K26-A2) and 2 times (K29-A2). Furthermore, the NEs inhibited these isolates biofilms formation. The NEs showed a MBIC ranging from 15.625 to 250 µg/mL. Thus, the NEs showed physicochemical characteristics suitable for future clinical trials, enhancing the CAZ antibacterial and antibiofilm activity, thus becoming a promising strategy for the treatment of bacterial infections caused by multidrug-resistant K. pneumoniae. KEY POINTS: • The NEs showed physicochemical characteristics suitable for future clinical trials. • The NEs showed a synergistic/additive profile, when associated with ceftazidime. • The NEs inhibited biofilm formation of clinical isolates.

Eight weeks of daily cottonseed oil intake attenuates postprandial angiopoietin-like proteins 3 and 4 responses compared to olive oil in adults with hypercholesterolemia: A secondary analysis of a randomized clinical trial.

Angiopoietin-like proteins (ANGPTLs) -3, -4, and -8 are regulators of lipid metabolism and have been shown to respond to changes in dietary fats. It is unknown how ANGPTLs respond to cottonseed oil (CSO) and olive oil (OO) consumption in a population with hypercholesterolemia. The purpose of this study was to determine the impact of CSO vs. OO consumption on fasting and postprandial ANGPTL responses in adults with hypercholesterolemia. We hypothesized that CSO would have lower fasting and postprandial ANGPTL responses compared with OO. Forty-two adults with high cholesterol completed a single-blind, randomized trial comparing CSO (n = 21) vs. OO (n = 21) diet enrichment. An 8-week partial outpatient feeding intervention provided ∼60% of the volunteers' total energy expenditure (∼30% of total energy expenditure as CSO or OO). The remaining 40% was not controlled. Fasting blood draws were taken at pre-, mid-, and postintervention visits. Volunteers consumed a high saturated fat meal followed by 5 hours of blood draws pre- and postvisits. Fasting ANGPTL3 had a marginally significant treatment by visit interaction (P = .06) showing an increase from pre- to postintervention in CSO vs. OO (CSO: 385.1 ± 27.7 to 440.3 ± 33.9 ng/mL; OO: 468.2 ± 38.3 to 449.2 ± 49.5 ng/mL). Both postprandial ANGPTL3 (P = .02) and ANGPTL4 (P < .01) had treatment by visit interactions suggesting increases from pre- to postintervention in OO vs. CSO with no differences between groups in ANGPTL8. These data show a worsening (increase) of postprandial ANGPTLs after the OO, but not CSO, intervention. This aligns with previously reported data in which postprandial triglycerides were protected from increases compared with OO. ANGPTLs may mediate protective effects of CSO consumption on lipid control. This trial was registered at clinicaltrials.gov (NCT04397055).

Acute Antiplatelet Effects of an Oleocanthal-Rich Olive Oil in Type II Diabetic Patients: A Postprandial Study.

Postprandial dysmetabolism is a common entity of type 2 diabetes mellitus (T2DM) and may act as a daily stressor of the already dysfunctional diabetic platelets. This study aims to investigate whether oleocanthal-rich olive oils (OO), incorporated into a carbohydrate-rich meal, can affect postprandial dysmetabolism and platelet aggregation. Oleocanthal is a cyclooxygenase inhibitor with putative antiplatelet properties. In this randomized, single-blinded, crossover study, ten T2DM patients consumed five isocaloric meals containing 120 g white bread combined with: (i) 39 g butter, (ii) 39 g butter and 400 mg ibuprofen, (iii) 40 mL OO (phenolic content < 10 mg/Kg), (iv) 40 mL OO with 250 mg/Kg oleocanthal and (v) 40 mL OO with 500 mg/Kg oleocanthal. Metabolic markers along with ex vivo ADP- and thrombin receptor-activating peptide (TRAP)-induced platelet aggregation were measured before and for 4 h after the meals. The glycemic and lipidemic response was similar between meals. However, a sustained (90-240 min) dose-dependent reduction in platelets' sensitivity to both ADP (50-100%) and TRAP (20-50%) was observed after the oleocanthal meals in comparison to OO or butter meals. The antiplatelet effect of the OO containing 500 mg/Kg oleocanthal was comparable to that of the ibuprofen meal. In conclusion, the consumption of meals containing oleocanthal-rich OO can reduce platelet activity during the postprandial period, irrespective of postprandial hyperglycemia and lipidemia.

Exploring the Potential of Wild Olive (Acebuche) Oil as a Pharm-Food to Prevent Ocular Hypertension and Fibrotic Events in the Retina of Hypertensive Mice.

SCOPE: Our laboratory has previously described the antioxidant and anti-inflammatory potential of a wild olive (acebuche, ACE) oil against hypertension-associated vascular retinopathies. The current study aims to analyze the antifibrotic effect of ACE oil on the retina of hypertensive mice. METHODS AND RESULTS: Mice are rendered hypertensive by administration of NG-nitro-L-arginine-methyl-ester (L-NAME) and simultaneously subjected to dietary supplementation with ACE oil or a reference extra virgin olive oil (EVOO). Intraocular pressure (IOP) is measured by rebound tonometry, and retinal vasculature/layers are analyzed by fundus fluorescein angiography and optical coherence tomography. Different fibrosis-related parameters are analyzed in the retina and choroid of normotensive and hypertensive mice with or without oil supplementation. Besides preventing the alterations found in hypertensive animals, including increased IOP, reduced fluorescein signal, and altered retinal layer thickness, the ACE oil-enriched diet improves collagen metabolism by regulating the expression of major fibrotic process modulators (matrix metalloproteinases, tissue inhibitors of metalloproteinases, connective tissue growth factor, and transforming growth factor beta family). CONCLUSION: Regular consumption of EVOO and ACE oil (with better outcomes in the latter) might help reduce abnormally high IOP values in the context of hypertension-related retinal damage, with significant reduction in the surrounding fibrotic process.

Hydroxytyrosol Induces Dyslipidemia in an ApoB100 Humanized Mouse Model.

SCOPE: Extra virgin olive oil has numerous cardiopreventive effects, largely due to its high content of (poly)phenols such as hydroxytyrosol (HT). However, some animal studies suggest that its excessive consumption may alter systemic lipoprotein metabolism. Because human lipoprotein metabolism differs from that of rodents, this study examines the effects of HT in a humanized mouse model that approximates human lipoprotein metabolism. METHODS AND RESULTS: Mice are treated as follows: control diet or diet enriched with HT. Serum lipids and lipoproteins are determined after 4 and 8 weeks. We also analyzed the regulation of various genes and miRNA by HT, using microarrays and bioinformatic analysis. An increase in body weight is found after supplementation with HT, although food intake was similar in both groups. In addition, HT induced the accumulation of triacylglycerols but not cholesterol in different tissues. Systemic dyslipidemia after HT supplementation and impaired glucose metabolism are observed. Finally, HT modulates the expression of genes related to lipid metabolism, such as Pltp or Lpl. CONCLUSION: HT supplementation induces systemic dyslipidemia and impaired glucose metabolism in humanized mice. Although the numerous health-promoting effects of HT far outweigh these potential adverse effects, further carefully conducted studies are needed.

Body weight gain and control: beneficial effect of extra virgin olive oil versus corn oil in an experimental model of mammary cancer.

Obesity is a known risk factor for breast cancer, the most common malignancy among women worldwide. We have previously described different effects of high-fat diets on mammary experimental carcinogenesis. In this work, we analyzed the animal growth data obtained in six experimental assays, in healthy and carcinogen-induced rats undergoing different dietary interventions. The animals were fed with three experimental diets administered at different periods of development: a control low-fat diet, and two isocaloric high-fat diets (rich in corn oil or in extravirgin olive oil -EVOO-). Weekly weight throughout the development of 818 animals have been compiled and reanalyzed using adjusted mathematical models. Molecular mechanisms have been investigated: ethanolamides in small intestine, neuropeptides controlling satiety in hypothalamus, and proteins controlling lipid metabolism in adipose and mammary tissues. The results indicated that the effect of diets depended on type of lipid, timing of intervention and health status. The high corn oil diet, but not the high EVOO diet, increased body weight and mass, especially if administered from weaning, in healthy animals and in those that received a moderate dose of carcinogen. The potential protective effect of EVOO on weight maintenance may be related to anorexigenic neuropeptides such as oxytocin and lipolysis/deposition balance in adipose tissue (increasing phospho-PKA, HSL, MGL and decreasing FAS). In animals with cancer, body weight gain was related to the severity of the disease. Taken together, our results suggest that EVOO has a beneficial effect on body weight maintenance in both health and cancer.

Protective role of olive oil extract of propolis on short and long-term administration of tamoxifen in rats.

Tamoxifen (TAM) is an antiestrogenic agent used for adjuvant treatment in estrogen receptor-positive breast cancers in the pre/post-menopausal period. This study, it was aimed to determine the effect of olive oil extract of propolis (OEP) on short and long-term administration of TAM in rats. Wistar albino rats were divided into groups with eight animals in each. Groups: control, OEP, TAM, and OEP + TAM. At the end of the experiment, oxidative stress tests were performed with Enzyme-Linked ImmunoSorbent Assay (ELISA) on blood and tissue samples (liver, kidney, and ovary) taken from rats. After single-dose TAM administration, there was a significant increase in red blood cell, hematocrit, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration levels compared to the control group, a decrease in low-density lipoprotein (LDL) value, a significant increase in liver enzymes and fasting glucose values was detected compared with the control and propolis groups. A normalizing effect was observed in the group given OEP and TAM combined. The increase in Malondialdehyde (MDA) and the decrease in enzyme activities in tissues are also noteworthy. Propolis application reduced the tissue damage caused by TAM. In addition, improved cytokine levels, which increased with TAM administration. It has been concluded that OEP can be given in supportive treatment, as it improves hematological and antioxidant parameters in TAM treatment.

Comparative Efficacy of Red Beetroot Extract and Ozonated Olive Oil on Wound Healing in Rats.

OBJECTIVE: To compare and assess the effect of red beetroot extract and ozonated olive oil on wound healing in rats. STUDY DESIGN: Experimental study. Place and Duration of the Study: Department of Experimental Animal Research Laboratory, Faculty of Medicine, Aydin Adnan Menderes University, from June to July 2021. METHODOLOGY: Twenty-one, female Wistar albino rats were divided into 3 groups; red beetroot extract group (RBG, n=7), ozonated olive oil group (OOG, n=7), and physiological saline group (CG). Three round wound areas of similar shapes were produced on the back areas. Skin incisions with a diameter of 15 mm were made in rats with a scalpel under anaesthesia protocol. Beetroot extract was applied to RBG, ozonated olive oil to OOG, and saline to CG, once a day for 21 days. Tissue samples were taken from the wounds on the 3rd, 10th, and 21st day of the study, and a histopathological examination (Hematoxylin eosin staining) was performed for haemorrhage, congestion, necrosis, inflammation and fibrosis levels. Wound healing was also determined macroscopically by photography on same days. Serum oxidant (TOS, µmol H2O2 equivalents/L), antioxidant status (TAS, mmol trolox equivalents/L), serum total thiol (µmol/L), serum native thiol (µmol/L) and paraoxonase (PON, U/L) were determined from blood samples on the 21st day. RESULTS: Lower inflammation and higher blood antioxidant levels were determined in the RGB and OOG groups compared to the CG. A better wound healing on histology was observed in the OOG group compared to RGB. CONCLUSION: Red beetroot extract and ozonated olive oil enhanced wound healing in female rats. Ozonated olive oil had more effective wound-healing effect than beetroot extract. KEY WORDS: Wound healing, Ozonated olive oil, Red beetroot extract, Antioxidant effect.

The effectiveness of organic vegetable oils with high biocompatibility in preventing epidural fibrosis: An experimental study.

Background and purpose:

Epidural fibrosis after all spinal surgeries is an important surgical issue. Various biological and non-biological materials have been tried to inhibit epidural fibrosis, which is deemed to be the most important cause of pain after spinal surgery. Olive oil, nigella sativa oil and soybean oil employed in oral nutrition in clinics involving liquid fatty acids, palmatic acid, linoleic acid, stearic acid and palmitoleic acid. The effectiveness of olive oil, nigella sativa oil and soybean oil on epidural fibrosis was researched on for the first time in laminectomy model.

Fifty adult male Wistar albino rats weighing between 300 and 400 grams were used in the research. A total of 5 groups were formed: sham (Group I) (n = 10), no application was created; Group II (n = 10) 1 cc saline; Group III (n = 10) 1 cc olive oil; Group IV (n = 10) 1 cc nigella sativa oil; Group V (n = 10); 1 cc soybean oil was applied topically to the epidural region after laminectomy. The total spine of the rats was dissected, histopathological and immuno­chemical measurements were conducted. Neuro-histopathological results were scored semi-quantitatively in terms of vascular modification, neuron degeneration, gliosis and bleeding criteria.

The lowest level of fibrosis and connective tissue proliferation was observed in the group where nigella sativa oil was used after the operation, followed by the group treated with olive oil and lastly with the group given soybean oil.

Nigella sativa oil and olive oil are very efficient for lowering the degree of epidural fibrosis and adhesions following laminectomy and can be employed as a simple, inexpensive and highly biocompatible material in clinical practice.

Effect of Intake of Extra Virgin Olive Oil on Mortality in a South Italian Cohort with and without NAFLD.

BACKGROUND: Extra-virgin olive oil (EVOO) is the main source of seasoning fat in the Mediterranean diet and it is one of the components with known protective factors on chronic-degenerative disease. We aimed to evaluate the effect of a medium-high level of oil consumption on mortality in a cohort with good adherence to the Mediterranean diet. METHODS: A total of 2754 subjects who had completed the food questionnaire in the Multicenter Italian study on Cholelithiasis (MICOL) cohort were included in the study. EVOO consumption was categorized in four levels (<20 g/die, 21-30 g/die, 31-40 g/die, >40 g/die). We performed a flexible parametric survival model to assess mortality by EVOO consumption level adjusted for some covariates. We also performed the analysis on subjects with and without non-alcoholic fatty liver disease (NAFLD) to evaluate the effects of oil in this more fragile sub-cohort. RESULTS: We found a statistically significant negative effect on mortality for the whole sample when EVOO consumption was used, both as a continuous variable and when categorized. The protective effect was stronger in the sub-cohort with NAFLD, especially for the highest levels of EVOO consumption (HR = 0.58 with p < 0.05). CONCLUSIONS: Our study has shown a protective effect of EVOO consumption towards all causes of mortality. Despite the higher caloric intake, the protective power is greater for a consumption >40 g/day in both the overall cohort and the sub-cohorts with and without NAFLD.

EVOO supplement prevents type 1 diabetes by modulating gut microbiota and serum metabolites in NOD mice.

AIMS: Extra virgin olive oil (EVOO) is the highest quality olive oil available and has been shown to regulate postprandial blood glucose in patients with type 1 diabetes (T1D). However, it remains uncertain whether EVOO can prevent the onset of T1D. In this study, we investigated the potential preventive effect of orally administered EVOO on T1D in non-obese diabetic (NOD) mice. MAIN METHODS: We analyzed changes in fecal microbes using 16 s rDNA sequencing and serum metabolites using Ultra High-Performance Liquid Chromatography and Quadrupole Time-of-Flight Mass Spectrometry (Q-TOF-MS). KEY FINDINGS: Our findings showed that EVOO supplementation in NOD mice slowed gastric emptying, reduced insulitis, and delayed T1D onset. Moreover, EVOO altered the composition of fecal microbes, increasing the Bacteroidetes/Firmicutes ratio, and promoting the growth of short-chain fatty acids (SCFAs)-producing bacteria, such as Lachnoclostridium and Ruminococcaceae_UCG-005. Moreover, it also increased beneficial serum metabolites, including unsaturated fatty acid and triterpenoid, which positively correlated with the increased SCFA-producing bacteria and negatively correlated with the disease indicators. Conversely, most decreased serum lipid metabolites, such as Oleamide, showed the opposite trend. SIGNIFICANCE: Our study demonstrates that EVOO may ameliorate pancreas inflammation and prevent T1D onset in NOD mice by modulating gut microbiota and serum metabolites.

Metabolomic and Transcriptomic Analysis of Effects of Three MUFA-Rich Oils on Hepatic Glucose and Lipid Metabolism in Mice.

SCOPE: Olive oil, rapeseed oil, and lard are dietary fats rich in monounsaturated fatty acids, but the effects of dietary oils enriched in monounsaturated fatty acids on hepatic lipid deposition have seldom been compared. METHODS AND RESULTS: Ninety 8-week-old C57BL/6J male mice are randomly divided into six groups and fed diets containing lard, rapeseed oil, or olive oil with a 10% or 45% fat energy supply for 16 weeks. Under high-fat conditions, serum total cholesterol levels in the lard and olive oil groups are significantly higher than those in the rapeseed oil group. Hepatic lipid content in the olive oil group is higher than that in the other two groups. Compared with rapeseed oil, lard increases the liver levels of arachidonic, palmitic, and myristic acids and decreases the levels of eicosapentaenoic linolenic acid and linoleic acid. Olive oil increases the liver levels of docosatrienoic, arachidonic, oleic, and myristic acids; maltose; and fructose and decreases the levels of eicosapentaenoic, linolenic, and linoleic acids. CONCLUSION: Olive oil probably causes hepatic lipid deposition in mice, which may enhance hepatic lipid synthesis by activating the starch and sucrose metabolic pathways. By contrast, rapeseed oil shows a significant anti-lipid deposition effect on the liver.

Bioavailability and systemic transport of oleanolic acid in humans, formulated as a functional olive oil.

Evidence of the pharmacological activity of oleanolic acid (OA) suggests its potential therapeutic application. However, its use in functional foods, dietary supplements, or nutraceuticals is hindered by limited human bioavailability studies. The BIO-OLTRAD trial is a double-blind, randomized controlled study with 22 participants that received a single dose of 30 mg OA formulated as a functional olive oil. The study revealed that the maximum serum concentration of OA ranged from 500 to 600 ng mL-1, with an AUC0-∞ value of 2862.50 ± 174.50 ng h mL-1. Furthermore, we discovered a physiological association of OA with serum albumin and triglyceride-rich lipoproteins (TRL). UV absorption spectra showed conformational changes in serum albumin due to the formation of an adduct with OA. Additionally, we demonstrated that TRL incorporate OA, reaching a maximum concentration of 140 ng mL-1 after 2-4 hours. We conjecture that both are efficient carriers to reach target tissues and to yield high bioavailability.

The Immunomodulatory Effects of a 6-Month Extra Virgin Olive Oil Intervention on Monocyte Cytokine Secretion and Plasma Cytokine Levels in Dyslipidemic and Post-Infarct Patients: A Clinical Pilot Study.

Atherosclerosis is an immuno-inflammatory process underlying cardiovascular diseases. One of the main actors of this inflammation is monocytes, with the switch in their phenotypes and irregularities in their cytokine production. OBJECTIVE: This study was aimed to investigate the nutraceutical potential of extra virgin olive oil (EVOO) on the inflammatory status of monocytes in participants showing different levels of cardiovascular risk. METHODS: 43 participants 65-85 years old were recruited including 14 healthy, 12 dyslipidemic patients with hypercholesterolemia recently diagnosed, and 17 post-infarct patients. Participants from all groups were supplemented with EVOO (25 mL/day) for 6 months. IL-1ß, IL-6, IL-10, TNF-α cytokine production, and monocyte phenotypes were investigated both at quiescent and at stimulated state by flow cytometry. RESULTS: At the baseline (pre-intervention), dyslipidemic patients, compared to healthy and post-infarct participants, showed monocytes in an inflammatory state characterized by a significantly weaker IL-10 production. Our results do not show a significant modulation of the phenotype or IL-10, IL-6, and TNF-α production following a 6-month EVOO intake whether at quiescence or under stimulation. However, IL-1ß is significantly increased by the intervention of EVOO in post-infarct patients. Paradoxically after the 6-month intervention, monocytes from dyslipidemic patients showed a significantly decreased secretion of IL-1ß under LPS stimulation despite the increase observed at basal state. CONCLUSION: Our results show that 6-month EVOO intervention did not induce a monocyte phenotypic change or that this intervention significantly modifies cytokine production.