Claudio Galli

Low density lipoprotein oxidation is inhibited in vitro by olive oil constituents

Oxidation of low density lipoproteins maybe a factor in the development of atherosclerosis. The Mediterranean diet rich in vegetables, grains, legumes, fruits, and oils, mainly olive oil, has been suggested to reduce the incidence of coronary heart disease, because of its low saturated and high monounsaturated fatty acids content. It is also possible that the natural antioxidants in the oil help to prevent lipid oxidation, e.g. that of low density lipoproteins, thus retarding the formation of atherosclerotic plaques. First-pressed, extra-virgin olive oil contains appreciable amounts of polyphenolic compounds that prevent its autoxidation and are responsible for its high stability. We tested these compounds on low density lipoprotein oxidation and found an inhibitory effect, at low concentrations, on various indexes of lipid oxidation (vitamin E content, formation of thiobarbituric acid-reacting substances, lipid peroxides, levels of polyunsaturated fatty acids, protein modification, conjugated diene formation). Our data suggest that natural antioxidants could play a role in inhibiting the formation of cytotoxic products such as lipid peroxides thus retarding the onset of the atherosclerotic damage.

Inhibition of platelet aggregation and eicosanoid production by phenolic components of olive oil

This study was designed to investigate the in vitro effects of phenolic compounds extracted from olive oil and from olive derived fractions. More specifically, we investigated the effects on platelets of 2-(3,4-di-hydroxyphenyl)-ethanol (DHPE), a phenol component of extra-virgin olive oil with potent antioxidant properties. The following variables were studied: aggregation of platelet rich plasma (PRP) induced by ADP or collagen, and thromboxane B2 production by collagen or thrombin-stimulated PRP. In addition, thromboxane B2 and 12-hydroxyeicosatetraenoic acid (12-HETE) produced during blood clotting were measured in serum. Preincubation of PRP with DHPE for at least 10 min resulted in maximal inhibition of the various measured variables. The IC50s (concentration resulting in 50% inhibition) of DHPE for ADP or collagen-induced PRP aggregations were 23 and 67 microM, respectively. At 400 microM DHPE, a concentration which completely inhibited collagen-induced PRP aggregation, TxB2 production by collagen- or thrombin-stimulated PRP was inhibited by over 80 percent. At the same DHPE concentration, the accumulation of TxB2 and 12-HETE in serum was reduced by over 90 and 50 percent, respectively. We also tested the effects of PRP aggregation of oleuropein, another typical olive oil phenol, and of selected flavnoids (luteolin, apigenin, quercetin) and found them to be much less active. On the other hand a partially characterized phenol-enriched extract obtained from aqueous waste from olive oil showed rather potent activities. Our results are the first evidence that components of the phenolic fraction of olive oil can inhibit platelet function and eicosanoid formation in vitro, and that other, partially characterized, olive derivatives share these biological activities.

Olive oil phenolics are dose‐dependently absorbed in humans

Olive oil phenolic constituents have been shown, in vitro, to be endowed with potent biological activities including, but not limited to, an antioxidant action. To date, there is no information on the absorption and disposition of such compounds in humans. We report that olive oil phenolics, namely tyrosol and hydroxytyrosol, are dose‐dependently absorbed in humans after ingestion and that they are excreted in the urine as glucuronide conjugates. Furthermore, an increase in the dose of phenolics administered increased the proportion of conjugation with glucuronide.

Biological Properties of Olive Oil Phytochemicals

Referee: Dr. Joe Vinson, Chemistry Department, University of Scranton, Scranton, PA 18510 Olive oil is the principal source of fat in the Mediterranean diet, which has been associated with a lower incidence of coronary heart disease and certain cancers. Extra-virgin olive oil contains a considerable amount of phenolic compounds, for example, hydroxytyrosol and oleuropein, that are responsible for its peculiar taste and for its high stability. Evidence is accumulating to demonstrate that olive oil phenolics are powerful antioxidants, both in vitro and in vivo; also, they exert other potent biological activities that could partially account for the observed healthful effects of the Mediterranean diet.

Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages

The Mediterranean diet, rich in fresh fruits and vegetables, has been associated with a lower incidence of cardiovascular disease and cancer, partly because of its high proportion of bioactive compounds such as vitamins, flavonoids and polyphenols. The major lipid component of such diet is the drupe-derived olive oil, that can be distinguished from other seed oils for the peculiar composition of its non-triglyceride fraction. In fact, several minor components, including polyphenols, grant the oil its particular taste and aroma. Oleuropein, the most abundant among these components, has been shown to be a potent antioxidant endowed with antiinflammatory properties. We investigated the effects of oleuropein on NO release in cell culture and its activity toward nitric oxide synthase (iNOS) expression. The results show that oleuropein dose-dependently enhance nitrite production in LPS-challenged mouse macrophages. This effect was blocked by the iNOS inhibitor L-NAME, indicating increased iNOS activity. Also, Western blot analysis of cell homogenates show that oleuropein increases iNOS expression in such cells. Taken together, our data suggest that, during endotoxin challenge, oleuropein potentiates the macrophage-mediated response, resulting in higher NO production, currently believed to be beneficial for cellular and organismal protection.

Effects of dietary fatty acids on the fatty acid composition of brain ethanolamine phosphoglyceride : Reciprocal replacement of n-6 and n-3 polyunsaturated fatty acids

Abstract Pregnant rats were fed diets supplemented with oils rich either in n −6 (safflower oil) or in n −3 fatty acids (fish oil). This dietary treatment was continued with the weaned rats up to 90 days of age. The fatty acid composition of brain ethanolamine phosphoglyceride was analyzed at 15, 30, 60 and 90 days of age, in both groups of rats. It was confirmed that: 1. 1. Fatty acids of the n −6 and n −3 families undergo reciprocal replacement in the ethanolamine phosphoglyceride molecule according to the dietary levels of these acids. 2. 2. The desaturating steps in the metabolic conversion of linoleic ( n −6) acid are mainly affected in animals fed with high levels of n −3 acids. This is also true in brain. It was found that : 3. 3. Dietary polyunsaturated, long chain fatty acids of the n −3 family enter the brain and became involved in the metabolism of fatty acids of brain phospholipids. 4. 4. The levels of unsaturation of brain ethanolamine phosphoglyceride fatty acids is constant in both groups of rats.

Effects of fat and fatty acid intake on inflammatory and immune responses: a critical review.

intakes, and the relative relevance of direct AA intakes versus endogenous production, have not been fully assessed. • Formation of LC n–3 FA, especially to DHA, from ALA appears to be rather inefficient, although somewhat higher conversion rates have been shown in premenopausal women than in men [Giltay et al., 2004]. • There is competition between the two metabolic pathways, especially at the desaturation steps, and at the cellular level competition may also take place for the esterification into the 2 position of glycerol of glycerolipids, depending on the relative abundance of the competing FA [Visioli et al., 2006]. • Since the production of LC PUFA from precursors and of the transporters (e.g. lipoproteins) from the site of synthesis to cells takes place mainly in the liver, hepatic metabolism in relation to physiological states (e.g. neonates, pregnancy, ageing) and to pathological conditions may affect the overall availability of LC PUFA to cellular compartments. An additional relevant issue in the overall relationships between the intakes of LC PUFA, especially those that are present in very low amounts in the diet while being of unique nutritional importance, such as the LC n–3 PUFA, concerns their bioavailability in relation to the matrix (food vs. formulation). Available data indicate that elevation of circulating levels of these FA is greater when they are ingested as food components rather than as formuIntroduction

Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial

Objective To investigate whether dietary supplementation with docosahexaenoic acid (DHA) decreases liver fat content in children with non-alcoholic fatty liver disease (NAFLD). Design, setting and patients We performed a randomised controlled trial of DHA supplementation (250 and 500 mg/day) versus placebo in 60 children with biopsy-proven NAFLD (20 children per group). Main outcome measures The main outcome was the change in liver fat content as detected by ultrasonography after 6 months of treatment. Secondary outcomes were the changes in insulin sensitivity index, alanine transaminase, triglycerides and body mass index after 6 months of treatment. Results Blood DHA increased in children supplemented with DHA (0.65%, 95% CI 0.30% to 1.10% for the DHA 250 mg group and 1.15%, 0.87% to 1.43% for the DHA 500 mg group). The odds of more severe versus less severe liver steatosis after treatment was lower in children treated with DHA 250 mg/day (OR = 0.01, 0.002 to 0.11, p <0.001) and DHA 500 mg/day (OR = 0.04, 0.002 to 0.46, p = 0.01) as compared to placebo but there was no difference between the DHA groups (p = 0.4). Insulin sensitivity index increased and triglycerides decreased to a similar degree in both DHA groups as compared to placebo but there was no effect on alanine transaminase and body mass index. Conclusion DHA supplementation improves liver steatosis and insulin sensitivity in children with NAFLD.

Olive Phenol Hydroxytyrosol Prevents Passive Smoking–Induced Oxidative Stress

BackgroundOxidative stress is involved in the onset of several degenerative disorders, and epidemiological studies indicate that a high intake of dietary antioxidants, as in the case of the Mediterranean basin, is protective. Olive mill waste waters (OMWWs) are a byproduct of olive oil production rich in phenolic antioxidants, such as hydroxytyrosol. We tested the effects of a low dose of an OMWW extract in a model of sidestream smoke–induced oxidative stress in rats by evaluating the urinary excretion of 8-iso-prostaglandin (PG) F2&agr; (iPF2&agr;-III). Methods and ResultsAn OMWW extract (5 mg/kg, providing 414 &mgr;g/kg of hydroxytyrosol) was administered to rats daily for 4 days, during which time the animals were exposed to sidestream smoke for 20 minutes once a day. Daily urines were collected, and the urinary excretion of 8-iso-PGF2&agr; was evaluated as an index of oxidative stress–induced in vivo lipid peroxidation. The exposure of rats to passive smoking increased the urinary excretion of 8-iso-PGF2&agr; by 44±4.2% at 48 hours and by 55±10% at 96 hours. Treatment with the OMWW extract was able to completely prevent the increase at 48 hours and resulted in lower increments (34±18% versus 55±10%) of 8-iso-PGF2&agr; excretion at 96 hours. ConclusionsA low dose of hydroxytyrosol, administered through OMWW, reduces the consequences of sidestream smoke–induced oxidative stress in rats.

Fat and fatty acid terminology, methods of analysis and fat digestion and metabolism: a background review paper.

Fats, oils or lipids consist of a large number of organic compounds including fatty acids, monoacylglycerols, diacylglycerols, triacylglycerols (TGs), phospholipids (PLs), eicosanoids, resolvins, docosanoids, sterols, sterol esters, carotenoids, vitamin A and E, fatty alcohols, hydrocarbons and wax esters. Classically, lipids were defined as substances that are soluble in organic solvents. This is a loose definition and could include a number of non-lipid organic compounds. A novel definition and comprehensive system of classification of lipids were proposed in 2005 [Fahy et al., 2005]. The novel definition is chemically based and defines lipids as small hydrophobic or amphipathic (or amphiphilic) molecules that may originate entirely or in part by condensations of thioesters and/or isoprene units. The proposed lipid classification system enables the cataloguing of lipids and their properties in a way that is compatible with other macromolecular data bases. Using this approach, lipids from biological tissues have been divided into 8 categories, as shown in table 1 . Each category contains distinct classes and subclasses of molecules [Fahy et al., 2005]. Published online: September 15, 2009