{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:43:45Z","timestamp":1774658625080,"version":"3.50.1"},"reference-count":100,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology (FCT)","doi-asserted-by":"publisher","award":["UIDB\/05021\/2020"],"award-info":[{"award-number":["UIDB\/05021\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Applied Sciences"],"abstract":"<jats:p>This review explores the critical role of advanced metabolomic methodologies in interpreting the complex relationship between the bioactive compounds in olive oil and their health benefits. Olive oil, the cornerstone of the Mediterranean diet, is renowned for its numerous health benefits, including anti-inflammatory, antioxidant, and cardioprotective properties. This review begins with an overview of the importance of olive oil for nutrition and health, followed by a detailed discussion of the key metabolites that contribute to its therapeutic potential. It further explores the evolution of analytical techniques in metabolomics from traditional methods to cutting-edge technologies, such as mass spectrometry and nuclear magnetic resonance spectroscopy, which have enhanced our understanding of the complex composition of olive oil. This review highlights how these advanced analytical findings correlate with the known health properties of olive oil and presents case studies in which these methodologies have led to new insights. Finally, we address the challenges in standardizing these techniques and discuss future research directions, underscoring the significance of metabolomics in nutritional science and public health. This comprehensive analysis aims to provide a deeper understanding of the health benefits of olive oil, informed by the latest advancements in analytical methodologies.<\/jats:p>","DOI":"10.3390\/app14104203","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T11:31:52Z","timestamp":1715772712000},"page":"4203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Narrative Review of Metabolomic Insights into Olive Oil\u2019s Nutritional Value"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6353-5184","authenticated-orcid":false,"given":"Marta","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, School of Medicine and Biomedical Sciences (ICBAS), University of Porto (U.Porto), Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9949-5861","authenticated-orcid":false,"given":"Mar\u00eda","family":"Rodr\u00edguez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Biochemistry Area, Faculty of Environmental Sciences and Biochemistry, University of Castilla-La Mancha, Avenue Carlos III s\/n, 45071 Toledo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6075-0845","authenticated-orcid":false,"given":"Anna","family":"Calabr\u00f2","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90134 Palermo, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6942-3023","authenticated-orcid":false,"given":"Emma","family":"Burgos-Ramos","sequence":"additional","affiliation":[{"name":"Biochemistry Area, Faculty of Environmental Sciences and Biochemistry, University of Castilla-La Mancha, Avenue Carlos III s\/n, 45071 Toledo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-9529","authenticated-orcid":false,"given":"Giulia","family":"Accardi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90134 Palermo, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-6006","authenticated-orcid":false,"given":"Paula","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, School of Medicine and Biomedical Sciences (ICBAS), University of Porto (U.Porto), Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"iNOVA Media Lab, ICNOVA-NOVA Institute of Communication, NOVA School of Social Sciences and Humanities, Universidade NOVA de Lisboa, 1069-061 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"ref_1","unstructured":"Guzm\u00e1n \u00c1lvarez, J., Hern\u00e1ndez Rodr\u00edguez, P., G\u00f3mez Calero, J.A., and Lora Gonz\u00e1lez, A. (2020). Olivares de Espa\u00f1a: Recorrido por la Biograf\u00eda del Olivar, su Memoria y sus Paisajes, Almuzara."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/CIRCGENETICS.114.000635","article-title":"Pro12Ala polymorphism of the PPAR\u03b32 gene interacts with a mediterranean diet to prevent telomere shortening in the PREDIMED-NAVARRA randomized trial","volume":"8","author":"Razquin","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1136\/jnnp-2012-304792","article-title":"Mediterranean diet improves cognition: The PREDIMED-NAVARRA randomised trial","volume":"84","author":"Clavero","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1041203","DOI":"10.3389\/fnut.2022.1041203","article-title":"Olive oil consumption and risk of cardiovascular disease and all-cause mortality: A meta-analysis of prospective cohort studies","volume":"9","author":"Xia","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1016\/S0140-6736(22)00122-2","article-title":"Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): A randomised controlled trial","volume":"399","author":"Fuentes","year":"2022","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"801","DOI":"10.3233\/JAD-200405","article-title":"A Randomized Clinical Trial of Greek High Phenolic Early Harvest Extra Virgin Olive Oil in Mild Cognitive Impairment: The MICOIL Pilot Study","volume":"78","author":"Tsolaki","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1080\/004982599238047","article-title":"\u2018Metabonomics\u2019: Understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data","volume":"29","author":"Nicholson","year":"1999","journal-title":"Xenobiotica"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1800384","DOI":"10.1002\/mnfr.201800384","article-title":"Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies","volume":"63","author":"Ulaszewska","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cca.2022.12.016","article-title":"Insulin resistance in Alzheimer\u2019s disease: The genetics and metabolomics links","volume":"539","author":"Amin","year":"2023","journal-title":"Clin. Chim. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shibutami, E., and Takebayashi, T. (2021). A Scoping Review of the Application of Metabolomics in Nutrition Research: The Literature Survey 2000\u20132019. Nutrients, 13.","DOI":"10.3390\/nu13113760"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Ca\u00f1as, V., and Sim\u00f3, C. (2019). Food Metabolomics\u2014An Overview, Elsevier.","DOI":"10.1016\/B978-0-08-100596-5.22666-8"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12263-017-0587-x","article-title":"A scheme for a flexible classification of dietary and health biomarkers","volume":"12","author":"Gao","year":"2017","journal-title":"Genes Amp. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Boskou, D. (2015). Olive and Olive Oil Bioactive Constituents, AOCS Press.","DOI":"10.1016\/B978-1-63067-041-2.50007-0"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1097\/FJC.0b013e3181c5e7fd","article-title":"Olive oil and cardiovascular health","volume":"54","author":"Covas","year":"2009","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Jimenez-Lopez, C., Carpena, M., Louren\u00e7o-Lopes, C., Gallardo-Gomez, M., Lorenzo, J.M., Barba, F.J., Prieto, M.A., and Simal-Gandara, J. (2020). Bioactive Compounds and Quality of Extra Virgin Olive Oil. Foods, 9.","DOI":"10.3390\/foods9081014"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Simopoulos, A.P., and Visioli, F. (2007). More on Mediterranean Diets, Karger.","DOI":"10.1159\/isbn.978-3-318-01429-7"},{"key":"ref_17","first-page":"201","article-title":"An overview of the modulatory effects of oleic acid in health and disease","volume":"13","author":"Souza","year":"2013","journal-title":"Mini. Rev. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13811","DOI":"10.1073\/pnas.0807500105","article-title":"Oleic acid content is responsible for the reduction in blood pressure induced by olive oil","volume":"105","author":"Benet","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1080\/10408398.2020.1854673","article-title":"Dietary oleic acid supplementation and blood inflammatory markers: A systematic review and meta-analysis of randomized controlled trials","volume":"62","author":"Wang","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s11154-020-09549-6","article-title":"Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning against insulin resistance and diabetes","volume":"21","author":"Rehman","year":"2020","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6053492","DOI":"10.1155\/2018\/6053492","article-title":"Omega-9 Oleic Acid, the Main Compound of Olive Oil, Mitigates Inflammation during Experimental Sepsis","volume":"2018","author":"Kurz","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"M\u00fcller, A.K., Albrecht, F., Rohrer, C., Koeberle, A., Werz, O., Schl\u00f6rmann, W., Glei, M., Lorkowski, S., and Wallert, M. (2021). Olive Oil Extracts and Oleic Acid Attenuate the LPS-Induced Inflammatory Response in Murine RAW264.7 Macrophages but Induce the Release of Prostaglandin E2. Nutrients, 13.","DOI":"10.3390\/nu13124437"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Santa-Mar\u00eda, C., L\u00f3pez-Enr\u00edquez, S., Montserrat-de la Paz, S., Geniz, I., Reyes-Quiroz, M.E., Moreno, M., Palomares, F., Sobrino, F., and Alba, G. (2023). Update on Anti-Inflammatory Molecular Mechanisms Induced by Oleic Acid. Nutrients, 15.","DOI":"10.3390\/nu15010224"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000448357","article-title":"Fatty Acid Oxidation and Its Relation with Insulin Resistance and Associated Disorders","volume":"68","author":"Lopaschuk","year":"2016","journal-title":"Ann. Nutr. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1161\/CIRCRESAHA.107.165472","article-title":"Role of mitochondrial dysfunction in insulin resistance","volume":"102","author":"Kim","year":"2008","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8152","DOI":"10.1002\/jcp.27603","article-title":"Insulin resistance: Review of the underlying molecular mechanisms","volume":"234","author":"Yaribeygi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.chemphyslip.2017.04.002","article-title":"Comparison of the effects of major fatty acids present in the Mediterranean diet (oleic acid, docosahexaenoic acid) and in hydrogenated oils (elaidic acid) on 7-ketocholesterol-induced oxiapoptophagy in microglial BV-2 cells","volume":"207","author":"Debbabi","year":"2017","journal-title":"Chem. Phys. Lipids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1750-3639.2010.00449.x","article-title":"Oleic acid ameliorates amyloidosis in cellular and mouse models of Alzheimer\u2019s disease","volume":"21","author":"Amtul","year":"2011","journal-title":"Brain Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4416","DOI":"10.1021\/acschemneuro.0c00639","article-title":"Elucidating the Neuroprotective Role of Formulated Camel \u03b1-Lactalbumin\u2013Oleic Acid Complex by Curating the SIRT1 Pathway in Parkinson\u2019s Disease Model","volume":"11","author":"Ubaid","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1081190","DOI":"10.3389\/fncel.2023.1081190","article-title":"Free fatty acids support oligodendrocyte survival in a mouse model of amyotrophic lateral sclerosis","volume":"17","author":"Maruyama","year":"2023","journal-title":"Front. Cell. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3389\/fnmol.2018.00131","article-title":"Profile of Arachidonic Acid-Derived Inflammatory Markers and Its Modulation by Nitro-Oleic Acid in an Inherited Model of Amyotrophic Lateral Sclerosis","volume":"11","author":"Trostchansky","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_32","first-page":"1860","article-title":"Antitumor effect of oleic acid; mechanisms of action: A review","volume":"27","author":"Carrillo","year":"2012","journal-title":"Nutr. Hosp."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s11947-012-0836-3","article-title":"The Production, Benefits, and Applications of Monoacylglycerols and Diacylglycerols of Nutritional Interest","volume":"6","author":"Feltes","year":"2013","journal-title":"Food Bioprocess Technol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.tifs.2019.12.032","article-title":"Diacylglycerol in food industry: Synthesis methods, functionalities, health benefits, potential risks and drawbacks","volume":"97","author":"Lee","year":"2020","journal-title":"Trends Food Sci. Technol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7313","DOI":"10.3390\/molecules15107313","article-title":"Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties","volume":"15","author":"Dai","year":"2010","journal-title":"Molecules"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Serreli, G., and Deiana, M. (2018). Biological Relevance of Extra Virgin Olive Oil Polyphenols Metabolites. Antioxidants, 7.","DOI":"10.3390\/antiox7120170"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s12967-014-0219-9","article-title":"Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: Focus on protection against cardiovascular and metabolic diseases","volume":"12","author":"Bulotta","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.jff.2014.09.001","article-title":"Biological activities of the natural antioxidant oleuropein: Exceeding the expectation\u2014A mini-review","volume":"18","author":"Hassen","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_39","first-page":"2218495","article-title":"Oleuropein: Chemistry, extraction techniques and nutraceutical perspectives-An update","volume":"2023","author":"Khalil","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s12012-014-9271-1","article-title":"Oleuropein Offers Cardioprotection in Rats with Acute Myocardial Infarction","volume":"15","author":"Janahmadi","year":"2015","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1093\/jn\/138.8.1411","article-title":"Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells","volume":"138","author":"Fabiani","year":"2008","journal-title":"J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jsps.2010.05.005","article-title":"Cardioprotective and neuroprotective roles of oleuropein in olive","volume":"18","author":"Omar","year":"2010","journal-title":"Saudi. Pharm. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.numecd.2006.09.001","article-title":"The effects of polyphenols in olive leaves on platelet function","volume":"18","author":"Singh","year":"2008","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/nbm.1370","article-title":"Metabonomic identification of novel biomarkers in doxorubicin cardiotoxicity and protective effect of the natural antioxidant oleuropein","volume":"22","author":"Andreadou","year":"2009","journal-title":"NMR Biomed."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Marcelino, G., Hiane, P.A., Freitas, K.C., Santana, L.F., Pott, A., Donadon, J.R., and Guimar\u00e3es, R.C.A. (2019). Effects of Olive Oil and Its Minor Components on Cardiovascular Diseases, Inflammation, and Gut Microbiota. Nutrients, 11.","DOI":"10.3390\/nu11081826"},{"key":"ref_46","first-page":"54","article-title":"Oleuropein as a novel anti-diabetic nutraceutical. An overview","volume":"1","author":"Annunziata","year":"2018","journal-title":"Arch. Diabetes Obes."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Butt, M.S., Tariq, U., Iahtisham Ul, H., Naz, A., and Rizwan, M. (2021). Neuroprotective effects of oleuropein: Recent developments and contemporary research. J. Food Biochem., 45.","DOI":"10.1111\/jfbc.13967"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.freeradbiomed.2013.11.029","article-title":"Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates mitochondrial abnormalities in obese mice","volume":"67","author":"Cao","year":"2014","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1039\/C3FO60677E","article-title":"Comparative evaluation of the metabolic effects of hydroxytyrosol and its lipophilic derivatives (hydroxytyrosyl acetate and ethyl hydroxytyrosyl ether) in hypercholesterolemic rats","volume":"5","author":"Tabernero","year":"2014","journal-title":"Food Funct."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"104506","DOI":"10.1016\/j.jff.2021.104506","article-title":"Potential role of hydroxytyrosol in neuroprotection","volume":"82","author":"Chen","year":"2021","journal-title":"J. Funct. Foods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1111\/1750-3841.14198","article-title":"Antitumor Perspectives of Oleuropein and Its Metabolite Hydroxytyrosol: Recent Updates","volume":"83","author":"Imran","year":"2018","journal-title":"J. Food. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"96","DOI":"10.3109\/19390211.2012.682644","article-title":"Mechanisms of action of phenolic compounds in olive","volume":"9","author":"Rafehi","year":"2012","journal-title":"J. Diet. Suppl."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Pojero, F., Aiello, A., Gervasi, F., Caruso, C., Ligotti, M.E., Calabr\u00f2, A., Procopio, A., Candore, G., Accardi, G., and Allegra, M. (2022). Effects of Oleuropein and Hydroxytyrosol on Inflammatory Mediators: Consequences on Inflammaging. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010380"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/ptr.2686","article-title":"Effects of hydroxytyrosol-20 on carrageenan-induced acute inflammation and hyperalgesia in rats","volume":"23","author":"Gong","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00210-009-0399-7","article-title":"Hydroxytyrosol inhibits pro-inflammatory cytokines, iNOS, and COX-2 expression in human monocytic cells","volume":"379","author":"Zhang","year":"2009","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s00210-005-1078-y","article-title":"Hydroxytyrosol, a phenolic compound from virgin olive oil, prevents macrophage activation","volume":"371","author":"Maiuri","year":"2005","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.jnutbio.2012.12.011","article-title":"Effect of olive oil phenols on the production of inflammatory mediators in freshly isolated human monocytes","volume":"24","author":"Rosignoli","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1700283","DOI":"10.1002\/mnfr.201700283","article-title":"Olive Oil Phenolics Prevent Oxysterol-Induced Proinflammatory Cytokine Secretion and Reactive Oxygen Species Production in Human Peripheral Blood Mononuclear Cells, Through Modulation of p38 and JNK Pathways","volume":"61","author":"Serra","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Souza, P.A., Marcadenti, A., and Portal, V.L. (2017). Effects of Olive Oil Phenolic Compounds on Inflammation in the Prevention and Treatment of Coronary Artery Disease. Nutrients, 9.","DOI":"10.3390\/nu9101087"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"754","DOI":"10.2174\/138161211795428911","article-title":"Molecular mechanisms of inflammation. Anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal","volume":"17","author":"Lucas","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.4103\/1673-5374.251327","article-title":"New neuroprotective perspectives in fighting oxidative stress and improving cellular energy metabolism by oleocanthal","volume":"14","author":"Angeloni","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Pang, K.-L., and Chin, K.-Y. (2018). The Biological Activities of Oleocanthal from a Molecular Perspective. Nutrients, 10.","DOI":"10.3390\/nu10050570"},{"key":"ref_63","unstructured":"Campos, M.R.S. (2019). Bioactive Compounds, Woodhead Publishing."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jff.2016.07.005","article-title":"The biological activities of natural lignans from olives and virgin olive oils: A review","volume":"26","author":"Gaforio","year":"2016","journal-title":"J. Funct. Foods"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/1438-9312(200210)104:9\/10<685::AID-EJLT685>3.0.CO;2-Q","article-title":"Nutritional and health aspects of olive oil","volume":"104","author":"Harwood","year":"2002","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lanza, B., and Ninfali, P. (2020). Antioxidants in Extra Virgin Olive Oil and Table Olives: Connections between Agriculture and Processing for Health Choices. Antioxidants, 9.","DOI":"10.3390\/antiox9010041"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.biopha.2005.06.005","article-title":"Alpha-tocopherol: Roles in prevention and therapy of human disease","volume":"59","author":"Tucker","year":"2005","journal-title":"Biomed. Pharmacother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/clc.22422","article-title":"Tocopherols in the Prevention and Treatment of Atherosclerosis and Related Cardiovascular Disease","volume":"38","author":"Mathur","year":"2015","journal-title":"Clin. Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/iub.2020","article-title":"Vitamin E: Regulatory role in the cardiovascular system","volume":"71","author":"Sozen","year":"2019","journal-title":"IUBMB Life"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"21","DOI":"10.21307\/ane-2021-003","article-title":"Effects of vitamin E on neurodegenerative diseases: An update","volume":"81","author":"Icer","year":"2021","journal-title":"Acta. Neurobiol. Exp."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.trac.2004.11.021","article-title":"Metabolomics: Current analytical platforms and methodologies","volume":"24","author":"Dunn","year":"2005","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_72","unstructured":"Bajoub, A., Carrasco-Pancorbo, A., Ouazzani, N., and Fern\u00e1ndez-Guti\u00e9rrez, A. (2014). Ultra Performance Liquid Chromatography Mass Spectrometry, CRC Press."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1021\/jf00055a010","article-title":"GC-MS evaluation of phenolic compounds in virgin olive oil","volume":"43","author":"Angerosa","year":"1995","journal-title":"J. Agric. Food Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6852","DOI":"10.3390\/molecules18066852","article-title":"Application and Analysis of the Folin Ciocalteu Method for the Determination of the Total Phenolic Content from Limonium Brasiliense L.","volume":"18","author":"Blainski","year":"2013","journal-title":"Molecules"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0021-9673(00)00455-6","article-title":"Chromatographic analysis of unsaponifiable compounds of olive oils and fat-containing foods","volume":"881","author":"Lercker","year":"2000","journal-title":"J. Chromatogr. A"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Lioupi, A., Nenadis, N., and Theodoridis, G. (2020). Virgin olive oil metabolomics: A review. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 1150.","DOI":"10.1016\/j.jchromb.2020.122161"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jchromb.2007.10.022","article-title":"LC-MS-based metabonomics analysis","volume":"866","author":"Lu","year":"2008","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.jbiotec.2005.12.012","article-title":"Current challenges and developments in GC\u2013MS based metabolite profiling technology","volume":"124","author":"Kopka","year":"2006","journal-title":"J. Biotechnol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Janson, J.C., and J\u00f6nsson, J.\u00c5. (2011). Protein Purification: Principles, High Resolution Methods, and Applications, Wiley.","DOI":"10.1002\/9780470939932"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Kazakevich, Y., and LoBrutto, R. (2007). HPLC for Pharmaceutical Scientists, John Wiley & Sons, Inc.","DOI":"10.1002\/0470087951"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/1541-4337.12408","article-title":"Nuclear Magnetic Resonance (NMR) Spectroscopy in Food Science: A Comprehensive Review","volume":"18","author":"Hatzakis","year":"2019","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1002\/mrc.1985","article-title":"31P NMR spectroscopy in the quality control and authentication of extra-virgin olive oil: A review of recent progress","volume":"45","author":"Dais","year":"2007","journal-title":"Magn. Reson. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1080\/19440049.2015.1084539","article-title":"Advances in high-resolution mass spectrometry based on metabolomics studies for food\u2014A review","volume":"32","author":"Rubert","year":"2015","journal-title":"Food Addit. Contam. Part A"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.foodres.2014.05.009","article-title":"Metabolite profiling of olive oil and thyme phenols after a sustained intake of two phenol-enriched olive oils by humans: Identification of compliance markers","volume":"65","author":"Romero","year":"2014","journal-title":"Food Res. Int."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00394-015-1071-2","article-title":"Gender differences in plasma and urine metabolites from Sprague-Dawley rats after oral administration of normal and high doses of hydroxytyrosol, hydroxytyrosol acetate, and DOPAC","volume":"56","author":"Ferreres","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s00394-020-02295-0","article-title":"Pharmacokinetics and bioavailability of hydroxytyrosol are dependent on the food matrix in humans","volume":"60","author":"Medina","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Sakavitsi, M.E., Breynaert, A., Nikou, T., Lauwers, S., Pieters, L., Hermans, N., and Halabalaki, M. (2022). Availability and Metabolic Fate of Olive Phenolic Alcohols Hydroxytyrosol and Tyrosol in the Human GI Tract Simulated by the In Vitro GIDM-Colon Model. Metabolites, 12.","DOI":"10.3390\/metabo12050391"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"125029","DOI":"10.1016\/j.talanta.2023.125029","article-title":"Qualitative and quantitative determination of phenols and their metabolites in urine by in-syringe solid-phase extraction and LC-MS\/MS analysis for evaluation of virgin olive oil metabolism","volume":"266","year":"2024","journal-title":"Talanta"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1124\/dmd.110.032821","article-title":"Antioxidant Activities of Hydroxytyrosol Main Metabolites Do Not Contribute to Beneficial Health Effects after Olive Oil Ingestion","volume":"38","author":"Khymenets","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Qusa, M.H., Abdelwahed, K.S., Hill, R.A., and El Sayed, K.A. (2023). S-(\u2212)-Oleocanthal Ex Vivo Modulatory Effects on Gut Microbiota. Nutrients, 15.","DOI":"10.3390\/nu15030618"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1021\/pr5007894","article-title":"Metabolomic pattern analysis after mediterranean diet intervention in a nondiabetic population: A 1- and 3-year follow-up in the PREDIMED study","volume":"14","author":"Llorach","year":"2015","journal-title":"J. Proteome. Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Menendez, J.A., Vazquez-Martin, A., Garcia-Villalba, R., Carrasco-Pancorbo, A., Oliveras-Ferraros, C., Fernandez-Gutierrez, A., and Segura-Carretero, A. (2008). tabAnti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO). BMC Cancer, 8.","DOI":"10.1186\/1471-2407-8-377"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jpba.2012.01.033","article-title":"Application of nanoLC-ESI-TOF-MS for the metabolomic analysis of phenolic compounds from extra-virgin olive oil in treated colon-cancer cells","volume":"63","author":"Ferragut","year":"2012","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.fct.2019.01.016","article-title":"Comparison survey of EVOO polyphenols and exploration of healthy aging-promoting properties of oleocanthal and oleacein","volume":"125","author":"Nikou","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"131918","DOI":"10.1016\/j.foodchem.2021.131918","article-title":"Influence of the extraction method on the recovery of bioactive phenolic compounds from food industry by-products","volume":"378","author":"Romero","year":"2022","journal-title":"Food Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"116153","DOI":"10.1016\/j.trac.2020.116153","article-title":"Chromatography-MS based metabolomics applied to the study of virgin olive oil bioactive compounds: Characterization studies, agro-technological investigations and assessment of healthy properties","volume":"135","year":"2021","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Vazquez-Aguilar, A., Sanchez-Rodriguez, E., Rodriguez-Perez, C., Rangel-Huerta, O.D., and Mesa, M.D. (2023). Metabolomic-Based Studies of the Intake of Virgin Olive Oil: A Comprehensive Review. Metabolites, 13.","DOI":"10.3390\/metabo13040472"},{"key":"ref_98","first-page":"109","article-title":"Metabolic flux analysis in systems biology of mammalian cells","volume":"127","author":"Niklas","year":"2012","journal-title":"Adv. Biochem. Eng. Biotechnol."},{"key":"ref_99","first-page":"E537","article-title":"Longitudinal studies","volume":"7","author":"Caruana","year":"2015","journal-title":"J. Thorac. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pcad.2015.04.003","article-title":"Benefits of the Mediterranean Diet: Insights From the PREDIMED Study","volume":"58","author":"Estruch","year":"2015","journal-title":"Prog. Cardiovasc. Dis."}],"container-title":["Applied Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3417\/14\/10\/4203\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:42:59Z","timestamp":1760107379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3417\/14\/10\/4203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":100,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["app14104203"],"URL":"https:\/\/doi.org\/10.3390\/app14104203","relation":{},"ISSN":["2076-3417"],"issn-type":[{"value":"2076-3417","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]}}}