Absorption, Distribution and Excretion
Olive oil is a functional food, which in addition to having a high level of monounsaturated fatty acids (MUFA), also contains multiple minor components, among them several phenolic compounds. Oleuropeine and its glycoside are the main sources of a simple phenol hydroxytyrosol with a strong antioxidant activity. Hydroxytyrosol is well absorbed in the gastrointestinal tract but its bioavailability is poor because an important first past metabolism both in gut and liver, leading to the formation of sulphate and glucuronide conjugates, to the extent that concentrations in body fluids of its free form are almost undetectable. This is a major drawback in our understanding of the antioxidant activity of this compound in vivo and the potential health benefits derived from its consumption. The picture is further compounded by the fact that hydroxytyrosol is also a dopamine metabolite and body fluids concentrations combine exogenous and endogenous sources.
Olive oil phenolic compounds are generally believed to have beneficial antioxidant effects, but little is known about characteristics of their postprandial bioavailability in natural olive oil at real-life doses. The aim of the present study was to determine the concentrations of olive oil phenolic compounds in urine collected over 24 hr (24 hr urine) after a bolus ingestion of 25 mL of olive oil with different phenolic content, and to demonstrate the effect of this real-life olive oil dose on postprandial levels of blood lipids and oxidative stress biomarkers, as well as to examine the beneficial effects of olive oil phenols. Oral fat loads of 25 mL olive oil with high, moderate, and low phenolic content were administered to 12 healthy male volunteers in a randomized, controlled, crossover trial. Tyrosol and hydroxytyrosol were absorbed in a dose-dependent manner according to the phenolic content of the olive oil administered. The administered dose of 25 mL, which is close to that used daily in Mediterranean countries, did not induce significant postprandial lipemia nor did it promote an increase of in vivo oxidation markers. With regard to plasma antioxidant enzymes, glutathione peroxidase activity decreased postprandially after low phenolic content olive oil ingestion; however this was not observed after intake of moderate and high phenolic content olive oils. The phenolic content of the olive oils administered may account for the protection of the endogenous antioxidant defenses at postprandial state after ingestion of moderate and high phenolic content olive oils.
In humans, ... hydroxytyrosol (3,4-dihydroxyphenylethanol; HT), one of the major antioxidant components of virgin olive oil, ... is present in lipoproteins involved in atherosclerotic processes and is excreted in the urine mainly as glucuronide-conjugate. The aim of /this/ present study was to elucidate, in humans, the metabolic fate of HT after ingestion of virgin olive oil. After administration of virgin olive oil, 24-hour urine collections of healthy volunteers were prepared for gas chromatography-mass spectrometry analyses in order to identify and quantify HT and its metabolites homovanillic alcohol (HVA1c) and homovanillic acid (HVA). The results indicate that this compound undergoes the action of catechol-O-methyl transferase (COMT), enzymes involved in the catecholamine catabolism, resulting in an enhanced excretion of HVA1c. ... A significant increase of HVA /was found/, indicating an oxidation of the ethanolic residue of HT and/or of HVA1c in humans. The excretion of both metabolites significantly correlated with the dose of administered HT.
.. Olive oil phenolics, namely tyrosol and hydroxytyrosol, are dose-dependently absorbed in humans after ingestion and ... are excreted in the urine as glucuronide conjugates. Furthermore, an increase in the dose of phenolics administered increased the proportion of conjugation with glucuronide.

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Metabolism / Metabolites
Acyl-CoA hydrolase activity in rats maintained on a high-carbohydrate diet for 5 wk was comparable to the activity observed on a high-fat (olive oil) diet.

Interactions
... Mice were fed liquid diets containing either corn oil (control, AIN-93) or olive oil (6.25 g/L) throughout experiments. Animals were treated with CCl(4) for 4 weeks intraperitoneally. The mRNA expression of TGF-beta1 and collagen 1alpha2 (col1alpha2) in the liver was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). The hepatic stellate cells (HSCs) were isolated from /C57BL/ mice, and co-cultured with either oleic acid (100 microM) or linoleic acid (100 microM) for 2 days. The expression of alpha-smooth muscle actin (alpha-SMA) was assessed by immunohistochemistry. In addition, the production of hydroxyproline was determined. Serum alanine aminotransferase levels and the mRNA expression of TGF-beta and collalpha2 were significantly reduced by treatment with olive oil. Dietary olive oil blunted the expression of alpha-SMA in the liver and liver injury and hepatic fibrosis were prevented by treatment with olive oil. The number of alpha-SMA positive cells was significantly lower in HSCs co-cultured with oleic acid than in those co-cultured with linoleic acid. Concentration of hydroxyproline in culture medium was significantly lower in cells co-cultured with oleic acid than in the control. Dietary olive oil prevents CCl(4)-induced tissue injury and fibrosis in the liver. Since oleic acid inhibited activation of HSCs, oleic acid may play a key role on this mechanism.
This study was conducted to determine whether the daily consumption for 84 days of tyrosol and hydroxytyrosol, the main olive oil phenolic compounds, and olive oil mill wastewater (OMWW), a byproduct of olive oil production, rich in micronutrients, may improve bone loss in ovariectomized /Wistar/ rats (an experimental model of postmenopausal osteoporosis) and in ovariectomized rats with granulomatosis inflammation (a model set up for senile osteoporosis). As expected, an induced chronic inflammation provoked further bone loss at total, metaphyseal, and diaphyseal sites in ovariectomized rats. Tyrosol and hydroxytyrosol prevented this osteopenia by increasing bone formation (p < 0.05), probably because of their antioxidant properties. The two doses of OMWW extracts had the same protective effect on bone ( p < 0.05), whereas OMWW did not reverse established osteopenia. In conclusion, polyphenol consumption seems to be an interesting way to prevent bone loss.
... To test the relevance of other components of oils in the prevention of atherosclerosis, two olive oils from the same cultivar devoid of soluble phenolic compounds were prepared using different procedures (pressure or centrifugation), characterized and fed to apolipoprotein E-deficient mice as 10% (w/w) of their diet. The 2 olive oils had similar levels of monounsaturated fatty acids and squalene, but they differed in their content of linoleic, phytosterols, tocopherols, triterpenes and waxes, which were particularly enriched in the test olive oil obtained by centrifugation. In mice that received a diet enriched in the olive oil derived through centrifugation, the progression of atherosclerosis was delayed compared to the mice that received standard olive oil. That effect was associated with decreases in plasma triglycerides, total and non-high-density lipoprotein cholesterol and isoprostane 8-iso-prostaglandin F(2alpha). /These/ results clearly indicate that the preparation of olive oil is crucial in determining its antiatherosclerotic effect, which extends beyond the presence of phenolic compounds. The test olive oil exerted its antiatherosclerotic effects by modifying plasma lipids and oxidative stress, and it might be a good candidate to replace other fats in functional foods.
The purpose of the present study was to analyse the association of olive oil and dietary restriction on lipid profile and myocardial antioxidant defenses. Male Wistar rats (180-200 g, n = 6) were divided into 4 groups: control ad libitum diet (C), 50% restricted diet (DR), fed ad libitum and supplemented with olive oil (3 mL/(kg x day)) (OO), and 50% restricted diet and supplemented with olive oil (DROO). After 30 days of treatments, OO, DR, and DROO groups had increased total cholesterol and high-density lipoprotein cholesterol concentrations. DR and DROO animals showed decreased low-density lipoprotein cholesterol. DROO had the lowest low-density lipoprotein cholesterol concentration. Total lipids and triacylglycerols were raised by dietary restriction and diminished by olive oil. OO rats had higher myocardial superoxide dismutase and lower catalase and glutathione peroxidase activities than C rats. DR and DROO showed enhanced cardiac superoxide dismutase, catalase, and glutathione peroxidase activities from the control. Olive oil supplementation alone improved the lipid profile but was more effective when coupled with dietary restriction. There was a synergistic beneficial action of dietary restriction and olive oil on serum lipids and myocardial antioxidant defences.
For more Interactions (Complete) data for Olive oil (19 total), please visit the HSDB record page.

Therapeutic Uses
... Olive oil and rapeseed oil /were tested as to whether they/ have different effects on cholesterol metabolism ... /In a/ short-term experimental study, with controlled diets, ... a total of nine volunteers with conventional ileostomies /were tested for/ two 3-day diet periods /on a/ controlled diet including 75 g of rapeseed oil or olive oil ... Cholesterol absorption, ileal excretion of cholesterol, and bile acids, serum levels of cholesterol and bile acid metabolites /were measured/. Differences between diets /were/ evaluated with Wilcoxon's signed rank sum test. Rapeseed oil diet contained 326 mg more plant sterols than the olive oil diet. Rapeseed oil tended to decrease cholesterol absorption by 11% (p = 0.050), and increased excretion of cholesterol, bile acids, and their sum as sterols by 9% (p = 0.021), 32% (p = 0.038), and 51% (p = 0.011) compared to olive oil. A serum marker for bile acid synthesis (7alpha-hydroxy-4-cholesten-3-one) increased by 28% (p = 0.038) within 10 h of consumption, and serum cholesterol levels decreased by 7% (p = 0.024), whereas a serum marker for cholesterol synthesis (lathosterol) as well as serum levels of plant sterols remained unchanged ... Rapeseed oil and olive oil have different effects on cholesterol metabolism. Rapeseed oil, tends to decrease cholesterol absorption, increases excretion of cholesterol and bile acids, increases serum marker of bile acid synthesis, and decreases serum levels of cholesterol compared to olive oil. This could in part be explained by different concentrations of natural plant sterols...
... Eighteen young, healthy men participated in a double-blinded randomized cross-over study (3 week intervention period) with 50 g of oil per 10 MJ incorporated into a constant diet. Plasma cholesterol, triacylglycerol, apolipoprotein B, and very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol concentrations were 10;-20% higher after consumption of the olive oil diet compared with the rapeseed oil and sunflower oil diets [analysis of variance (ANOVA), p < 0.05]. The size of IDL, VLDL, and LDL subfractions did not differ between the diets, whereas a significantly higher number (apolipoprotein B concentration) and lipid content of the larger and medium-sized LDL subfractions were observed after the olive oil diet compared with the rapeseed oil and sunflower oil diets (ANOVA, p < 0.05). Total HDL cholesterol concentration did not differ significantly, but HDL(2a) cholesterol was higher after olive oil and rapeseed oil compared with sunflower oil (ANOVA, p < 0.05).In conclusion, rapeseed oil and sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins as well as on the number and lipid content of LDL subfractions compared with olive oil. Some of the differences may be attributed to differences in the squalene and phytosterol contents of the oils.
/Experimental Therapy/ Olive oil is a major component of the Mediterranean diet suggested to be beneficial to counteract Alzheimer's disease. ... 6,947 /elderly subjects received/ a brief baseline food frequency questionnaire and repeated cognitive tests. Olive oil intake was categorized as none (22.7%), moderate (use for cooking or dressing, 39.9%) and intensive (use for both cooking and dressing, 37.4%). Associations between olive oil and cognitive outcomes were examined taking into account socio-economic factors, health behaviors, health measures and other dietary intakes. ... Participants with moderate or intensive use of olive oil compared to those who never used olive oil showed lower odds of cognitive deficit for verbal fluency and visual memory. For cognitive decline during the 4-year follow-up, the association with intensive use was significant for visual memory (adjusted OR = 0.83, 95% CI: 0.69-0.99) but not for verbal fluency (OR = 0.85, 95% CI: 0.70-1.03) in multivariate analysis ...
Dietary habits play an important role in healthy ageing. We have investigated the role of dietary patterns on overall mortality in a large series of Italian elderly, recruited in five EPIC cohorts in Northern (Varese and Turin), Central (Florence) and Southern Italy (Naples and Ragusa).A total of 5611 subjects (72.6 % women) aged 60 years or older, enrolled in 1993-1998, were prospectively followed (median 6.2 years), with 152 deaths (98 women). Four major dietary patterns were identified by using an exploratory factor analysis based on dietary information collected at enrollment. The associations between these dietary patterns and overall mortality were evaluated by Cox models adjusted for potential confounders. The 'Olive Oil & Salad' pattern, characterised by a high consumption of olive oil, raw vegetables, soups and poultry, emerged as being inversely associated with overall mortality in both crude and adjusted models. After adjustment for gender, age and caloric intake, overall mortality was reduced by approximately 50 % in the highest quartile and a significant trend emerged (p = 0.008). This association persisted after adjusting for several additional confounders (hazard ratio (HR) 0.50; 95 % CI 0.29, 0.86; p for trend = 0.02). An association of the 'Pasta & Meat' pattern (characterised by pasta, tomato sauce, red meat, processed meat, added animal fat, white bread and wine) with increased overall mortality was also suggested, but only for the highest quartile in a multivariate model. Dietary recommendations aimed at the Italian elderly population should support a dietary pattern characterised by a high consumption of olive oil, raw vegetables and poultry.
For more Therapeutic Uses (Complete) data for Olive oil (42 total), please visit the HSDB record page.

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Drug Warnings
/Infant, premature/ In the first period of life, premature infants need parenteral nutrition.... Lipid emulsions (LEs), which are a part of parenteral nutrition, are known as potent immunological modulators and may therefore influence the immune status of parenterally fed infants. The aim of the study was to compare tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 production in the peripheral blood mononuclear cells (PBMCs) of premature infants parenterally fed with 2 LEs: METHODS: Premature infants born at < 32 weeks' gestation and with a birth weight < 1500 g were randomized in a double-blind method within the first 48 hours of life to receive 1 of 2 lipid emulsions : olive oil (OO) or soybean oil (SO) based. At baseline and after 14 days, blood samples were collected, and PBMCs were isolated and then cultured for 48 hours in medium only and in the presence of anti-CD3 antibodies. ... Of 44 recruited infants, 38 completed the study, 18 in the OO group and 20 in the SO group. The cytokine synthesis profile before the LE introduction was the same in both groups (nonstimulated and anti-CD3-induced PBMC). In the succeeding 14 days of parenteral nutrition, TNF-alpha, IL-6, and IL-10 levels in nonstimulated PBMCs remained unchanged in both groups. In contrast, IL-6 production was significantly higher in the SO group. SO-based LE may promote an excess of IL-6 production, especially in the T cell-dependent way of PBMC activation (via anti-CD3). OO emulsion seems to be immunologically more neutral than SO emulsion.

1522.392

8001-25-0

170924183

Colorless to light yellow liquid

0.9135

0°C

225 °C

1.467-1.471

0

10

82

108

1300

0

NWUIOBPENFDKLG-UHFFFAOYSA-N

InChI=1S/C20H40O2.C20H38O2.C20H36O2.C20H34O2.C18H36O2/c4*1-3-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22-4-2;1-3-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20-4-2/h3-19H2,1-2H3;11-12H,3-10,13-19H2,1-2H3;8-9,11-12H,3-7,10,13-19H2,1-2H3;5-6,8-9,11-12H,3-4,7,10,13-19H2,1-2H3;3-17H2,1-2H3

ethyl hexadecanoate;ethyl octadeca-9,12-dienoate;ethyl octadecanoate;ethyl octadeca-9,12,15-trienoate;ethyl octadec-9-enoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 100 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)