Absorption, Distribution and Excretion
Olive oil is a functional food rich in monounsaturated fatty acids (MUFAs) and contains various trace components, including several phenolic compounds. Oleuropein and its glycosides are major sources of hydroxytyrosol, a simple phenolic compound with strong antioxidant activity. Hydroxytyrosol is well absorbed in the gastrointestinal tract, but its bioavailability is low due to significant first-pass metabolism in the intestine and liver, resulting in sulfate and glucuronide conjugates, leading to almost undetectable free concentrations in body fluids. This severely hinders our understanding of the compound's antioxidant activity and potential health benefits in vivo. Hydroxytyrosol is also a dopamine metabolite, and its concentration in body fluids includes both exogenous and endogenous sources, further complicating the situation. While phenolic compounds in olive oil are generally considered to have beneficial antioxidant effects, little is known about their postprandial bioavailability at real-life doses in natural olive oil. This study aimed to determine the concentration of olive oil phenolic compounds in urine (24-hour urine) within 24 hours after a single intake of 25 mL of olive oil with different phenolic contents, and to explore the effects of this real-life dose of olive oil on postprandial blood lipids and oxidative stress biomarkers, as well as the beneficial effects of olive oil phenols. A randomized, controlled, crossover trial design was used, with 12 healthy male volunteers orally ingesting 25 mL of olive oil with high, medium, or low phenolic contents. The absorption of tyrosol and hydroxytyrosol was dose-dependent depending on the phenolic content of the ingested olive oil. The 25 mL dose of olive oil ingested was close to the daily consumption in Mediterranean countries and did not cause a significant increase in postprandial blood lipids or promote an increase in oxidative markers. Regarding plasma antioxidant enzymes, glutathione peroxidase activity decreased postprandially after ingestion of low-phenolic olive oil; however, this phenomenon was not observed after ingestion of medium and high-phenolic olive oil. The protective effect of endogenous antioxidant defense mechanisms in the postprandial state after ingestion of medium and high-phenolic olive oil may be related to its phenolic content. In the human body, hydroxytyrosol (3,4-dihydroxyphenylethanol; HT) is one of the main antioxidant components of extra virgin olive oil. It is present in lipoproteins involved in the process of atherosclerosis and is primarily excreted in urine as a glucuronide conjugate. This study aimed to elucidate the metabolic pathway of HT after ingestion of extra virgin olive oil in humans. After healthy volunteers consumed extra virgin olive oil, 24-hour urine samples were collected and analyzed by gas chromatography-mass spectrometry to identify and quantify HT and its metabolites homovanillinol (HVA1c) and homovanillic acid (HVA). The results showed that these compounds are acted upon by catechol-O-methyltransferase (COMT), an enzyme involved in the catabolism of catecholamines, leading to increased excretion of HVA1c. …The significant increase in HVA indicates that the ethanol residues of HT and/or HVA1c are oxidized in the human body. The excretion of both metabolites was significantly correlated with the dose of HT administered.
...The phenolic compounds in olive oil, namely tyrosol and hydroxytyrosol, are absorbed by the body in a dose-dependent manner after ingestion and excreted in the urine as glucuronide conjugates. Furthermore, increasing the dose of phenolic compounds increases the proportion bound to glucuronides.

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Metabolism/Metabolites
The acyl-CoA hydrolase activity in rats fed a high-carbohydrate diet for 5 weeks was comparable to that in rats fed a high-fat (olive oil) diet.

Interactions
During the experiment, mice were fed liquid diets containing either corn oil (control group, AIN-93) or olive oil (6.25 g/L). Animals were treated with carbon tetrachloride (CCl₄) via intraperitoneal injection for 4 weeks. The mRNA expression of transforming growth factor-β1 (TGF-β1) and collagen 1α2 (col1α2) in the liver was detected using reverse transcription-polymerase chain reaction (RT-PCR). Hepatic stellate cells (HSCs) were isolated from C57BL/mice and co-cultured with oleic acid (100 μM) or linoleic acid (100 μM) for 2 days. The expression of α-smooth muscle actin (α-SMA) was detected using immunohistochemistry. Hydroxyproline production was also measured. Olive oil treatment significantly reduced serum alanine aminotransferase levels and the mRNA expression of TGF-β and col1α2. Dietary olive oil can inhibit the expression of α-SMA in the liver and prevent liver damage and liver fibrosis. Compared with hepatic stellate cells (HSCs) co-cultured with linoleic acid, the number of α-SMA-positive cells in HSCs co-cultured with oleic acid was significantly reduced. The concentration of hydroxyproline in the cell culture medium co-cultured with oleic acid was significantly lower than in the control group. Dietary olive oil can prevent carbon tetrachloride (CCl4)-induced liver tissue damage and fibrosis. Since oleic acid inhibits HSC activation, it may play a key role in this mechanism. This study aimed to determine whether daily intake of tyrosol and hydroxytyrosol (the main phenolic compounds of olive oil) and olive oil production byproducts rich in micronutrients—olive oil mill wastewater (OMWW)—for 84 consecutive days could improve bone loss in ovariectomized Wistar rats (an experimental model of postmenopausal osteoporosis) and ovariectomized rats with granulomatous inflammation (a model of senile osteoporosis). As expected, the induced chronic inflammation led to further reductions in total bone mass, metaphyseal bone mass, and diaphyseal bone mass in ovariectomized rats. Tyrosol and hydroxytyrosol prevented this bone loss by increasing bone formation (p < 0.05), likely due to their antioxidant properties. Both doses of olive oil extract showed the same protective effect on bone (p < 0.05), but the olive oil extract did not reverse existing osteoporosis. In conclusion, polyphenol intake appears to be an effective method for preventing bone loss. ...To examine the role of other oil components in preventing atherosclerosis, we prepared two olive oils from the same variety but without soluble phenolic compounds using different methods (pressure method or centrifugation) and characterized them. We then fed these two olive oils at a 10% (w/w) feed ratio to apolipoprotein E-deficient mice. The two olive oils had similar levels of monounsaturated fatty acids and squalene, but differed in the levels of linoleic acid, phytosterols, tocopherols, triterpenoids, and waxes, with the centrifuged olive oil being particularly rich in these components. Compared to mice fed standard olive oil, mice fed centrifuged olive oil showed a slower progression of atherosclerosis. This delayed effect was associated with a decrease in plasma triglycerides, total cholesterol, non-HDL cholesterol, and isoprostaglandin F2α. These results clearly indicate that the preparation method of olive oil is crucial to its anti-atherosclerotic effect, and this effect does not depend solely on the presence of phenolic compounds. This tested olive oil exerts its anti-atherosclerotic effect by modulating plasma lipids and oxidative stress, thus potentially becoming a good candidate to replace other fats in functional foods. This study aimed to analyze the effects of olive oil and dietary restriction on lipid profiles and myocardial antioxidant defense. Male Wistar rats (180-200 g, n = 6) were divided into four groups: a free-feeding control group (C), a 50% restricted diet group (DR), a free-feeding group supplemented with olive oil (OO, 3 mL/(kg·d)), and a 50% restricted diet group supplemented with olive oil (DROO). After 30 days of treatment, the concentrations of total cholesterol and HDL cholesterol increased in the OO, DR, and DROO groups. The concentrations of low-density lipoprotein cholesterol decreased in the DR and DROO groups. The DROO group had the lowest concentration of low-density lipoprotein cholesterol. Dietary restriction increased total lipid and triglyceride levels, while olive oil decreased them. Compared to group C, rats in group OO had higher myocardial superoxide dismutase activity and lower catalase and glutathione peroxidase activities. Compared to the control group, the activities of cardiac superoxide dismutase, catalase, and glutathione peroxidase were all enhanced in groups DR and DROO. Olive oil supplementation alone can improve lipid profiles, but its effect is better when used in combination with dietary restriction. Dietary restriction and olive oil have a synergistic effect on lipids and myocardial antioxidant defense. For more complete data on interactions with olive oil (19 in total), please visit the HSDB record page.

Therapeutic Uses
...Olive oil and canola oil were tested to determine if their effects on cholesterol metabolism differed... In a short-term experimental study, nine volunteers undergoing routine ileostomy underwent two 3-day dietary tests, with the diet control including 75 grams of canola oil or olive oil... Cholesterol absorption, ileal cholesterol and bile acid excretion, and serum cholesterol and bile acid metabolite levels were measured. The Wilcoxon signed-rank test was used to assess differences between the different diets. The canola oil diet contained 326 mg more phytosterols than the olive oil diet. Compared to olive oil, canola oil tended to reduce cholesterol absorption by 11% (p = 0.050) and increase the excretion of cholesterol, bile acids, and their total (in sterol form) by 9% (p = 0.021), 32% (p = 0.038), and 51% (p = 0.011), respectively. Within 10 hours of consuming rapeseed oil, serum markers of bile acid synthesis (7α-hydroxy-4-cholesten-3-one) increased by 28% (p = 0.038), and serum cholesterol levels decreased by 7% (p = 0.024), while serum markers of cholesterol synthesis (lanosterol) and phytosterols remained unchanged… Rapeseed oil and olive oil have different effects on cholesterol metabolism. Compared to olive oil, rapeseed oil tends to reduce cholesterol absorption, increase cholesterol and bile acid excretion, increase serum bile acid synthesis marker levels, and decrease serum cholesterol levels. This may be partly attributed to differences in the concentration of natural phytosterols… Eighteen young, healthy men participated in a double-blind, randomized crossover study (intervention period of 3 weeks) in which 50 g/10 MJ of oil was added to their constant diet. Compared with rapeseed oil and sunflower oil diets, the olive oil diet resulted in a 10% to 20% increase in plasma cholesterol, triglycerides, apolipoprotein B, and very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) cholesterol concentrations [ANOVA, p < 0.05]. There were no significant differences in the size of IDL, VLDL, and LDL subfractions among the different dietary regimens, but compared with the rapeseed oil and sunflower oil diets, the olive oil diet significantly increased the number (apolipoprotein B concentration) and lipid content of large and medium LDL subfractions (ANOVA, p < 0.05). There were no significant differences in total HDL cholesterol concentration, but the HDL(2a) cholesterol levels were higher in the olive oil and rapeseed oil diets than in the sunflower oil diet (ANOVA, p < 0.05). In summary, rapeseed oil and sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins, as well as the quantity and lipid content of LDL subfractions, compared to olive oil. Part of the difference may be attributed to variations in squalene and phytosterol content among the different oils. /Experimental Therapy/ Olive oil is a major component of the Mediterranean diet, which is believed to help combat Alzheimer's disease. …6947 older participants underwent a short baseline food frequency questionnaire and repeated cognitive tests. Olive oil intake was categorized into three groups: no intake (22.7%), moderate intake (used for cooking or seasoning, 39.9%), and high intake (used for cooking and seasoning, 37.4%). The study examined the association between olive oil and cognitive outcomes, taking into account socioeconomic factors, health behaviors, health indicators, and other dietary intakes. …Participants who consumed moderate or high amounts of olive oil had a lower likelihood of cognitive deficits in verbal fluency and visual memory compared to participants who never consumed olive oil. During a 4-year follow-up period, multivariate analysis showed a significant association between high-intensity use and cognitive decline, particularly in visual memory (adjusted OR = 0.83, 95% CI: 0.69–0.99), but no significant association in verbal fluency (OR = 0.85, 95% CI: 0.70–1.03). Dietary habits play a crucial role in healthy aging. We investigated the impact of dietary patterns on overall mortality in older Italians. These older adults came from five EPIC cohorts in northern (Varese and Turin), central (Florence), and southern (Naples and Ragusa) Italy. A total of 5,611 participants aged 60 years and older (72.6% women) were enrolled between 1993 and 1998 and underwent prospective follow-up (median 6.2 years), of whom 152 died (98 women). Based on dietary information collected at enrollment, four major dietary patterns were identified through exploratory factor analysis. The association between these dietary patterns and all-cause mortality was assessed using a Cox proportional hazards model, adjusted for potential confounding factors. The “olive oil and salad” dietary pattern, characterized by high intakes of olive oil, raw vegetables, soups, and poultry, was negatively associated with all-cause mortality in both the unadjusted and adjusted models. After adjusting for sex, age, and calorie intake, all-cause mortality was reduced by approximately 50% in the top quartile, exhibiting a significant trend (p = 0.008). This association persisted after adjusting for several other confounding factors (hazard ratio (HR) 0.50; 95% confidence interval 0.29–0.86; trend test p = 0.02). One study also showed that the “pasta and meat” dietary pattern (characterized by pasta, tomato sauce, red meat, processed meats, added animal fats, white bread, and wine) was associated with increased overall mortality, but this association was observed only in the top quartile in the multivariate model. Dietary recommendations for older Italians should support a dietary pattern characterized by high intakes of olive oil, raw vegetables, and poultry.
For more complete data on the therapeutic uses of olive oil (42 types), please visit the HSDB record page.

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Drug Warning
/Preterm Infants/ Preterm infants require parenteral nutrition in early life… As part of parenteral nutrition, lipid emulsions (LEs) are known potent immunomodulators and may therefore affect the immune status of parenteral-fed infants. This study aimed to compare the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in peripheral blood mononuclear cells (PBMCs) of preterm infants after parenteral feeding with two lipid emulsions. Methods: Preterm infants with a gestational age <32 weeks and a birth weight <1500 g were randomly assigned to two groups within 48 hours of birth and received one of two lipid emulsions in a double-blind manner: olive oil (OO) group and soybean oil (SO) group. Blood samples were collected at baseline and 14 days later, PBMCs were isolated, and cultured for 48 hours in culture medium containing only culture medium and culture medium containing anti-CD3 antibody. A total of 44 infants were recruited, of whom 38 completed the study (18 in the OO group and 20 in the SO group). Prior to the introduction of LE, the cytokine synthesis profiles of the two groups (unstimulated and anti-CD3-induced PBMCs) were identical. During the subsequent 14 days of parenteral nutrition, the levels of TNF-α, IL-6, and IL-10 in the unstimulated PBMCs of both groups remained unchanged. In contrast, the SO group showed significantly higher IL-6 production. SO-based LE may promote excessive IL-6 production, particularly in the T-cell-dependent PBMC activation pathway (via anti-CD3). The OO emulsion appeared to be more immune-neutral than the 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.)