{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T04:54:55Z","timestamp":1776488095527,"version":"3.51.2"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["Ricerca Corrente 2025\/2026"],"award-info":[{"award-number":["Ricerca Corrente 2025\/2026"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) refers to fatty liver disease associated with metabolic syndrome. MASLD causes alterations in lipid metabolism, which can be regulated with a diet rich in polyphenols. The present study aims to evaluate the effects of daily consumption of 400 g of \u201cNavelina\u201d oranges for 4 weeks on serum lipid profiles in a group of 60 patients with MASLD, to identify specific lipid species associated with improvements in hepatic steatosis. Methods: Blood samples were collected from all participants, and biochemical measurements and a serum lipidomic profile were performed. Finally, a Spearman correlation analysis was used to assess the relationships between serum lipidomic fatty acids and biochemical lipid markers. Results: In the experimental treatment arm, serum lipidomic analysis showed a slight decrease in Arachidonic acid (AA) and the Arachidonic acid\/Eicosapentaenoic acid ratio (AA\/EPA ratio) but no significant interaction between time and treatment was detected. In the same group, Oleic acid, MUFAs and the AA\/EPA ratio were significantly and negatively correlated with HDL (r = \u22120.368, p = 0.046), (r = \u22120.384, p = 0.036), and (r = \u22120.522, p = 0.003), respectively. Conversely, EPA and n-3 PUFAs were positively and significantly correlated with HDL (r = 0.447, p = 0.013) and (r = 0.403, p = 0.027) respectively. Conclusions: Furthermore, this study represents one of the first clinical trials to shed a light on the potential association of \u201cNavelina\u201d orange polyphenols on serum fatty acid profiles in patients with MASLD, supporting studies on the nutraceutical effect of oranges on lipid metabolism.<\/jats:p>","DOI":"10.3390\/nu18081254","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:14:46Z","timestamp":1776334486000},"page":"1254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of 4-Week Consumption of \u201cNavelina\u201d Oranges on Serum Lipid Profile in Patients with MASLD: Evidence from a Randomized Clinical Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7912-9023","authenticated-orcid":false,"given":"Valentina","family":"De Nunzio","sequence":"first","affiliation":[{"name":"Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, 70013 Castellana Grotte, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9042-7082","authenticated-orcid":false,"given":"Giuliano","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, 70013 Castellana Grotte, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3291-3686","authenticated-orcid":false,"given":"Davide","family":"Guido","sequence":"additional","affiliation":[{"name":"Data Science Unit, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, 70013 Castellana Grotte, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2969-5052","authenticated-orcid":false,"given":"Emanuela","family":"Aloisio Caruso","sequence":"additional","affiliation":[{"name":"Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, 70013 Castellana Grotte, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-7832","authenticated-orcid":false,"given":"Miriam","family":"Cofano","sequence":"additional","affiliation":[{"name":"Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, 70013 Castellana Grotte, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5909-057X","authenticated-orcid":false,"given":"Ilenia","family":"Saponara","sequence":"additional","affiliation":[{"name":"Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, 70013 Castellana Grotte, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1218-599X","authenticated-orcid":false,"given":"Matteo","family":"Centonze","sequence":"additional","affiliation":[{"name":"Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, 70013 Castellana Grotte, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Grazia","family":"Refolo","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pathology, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, 70013 Castellana Grotte, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-2198","authenticated-orcid":false,"given":"Maria","family":"Notarnicola","sequence":"additional","affiliation":[{"name":"Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, 70013 Castellana Grotte, Italy"},{"name":"Laboratory of Clinical Pathology, National Institute of Gastroenterology IRCCS \u201cSaverio de Bellis\u201d, 70013 Castellana Grotte, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1016\/j.cgh.2020.10.046","article-title":"Impact of the New Definition of Metabolic Associated Fatty Liver Disease on the Epidemiology of the Disease","volume":"19","author":"Wong","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Boccatonda, A., Andreetto, L., D\u2019Ardes, D., Cocco, G., Rossi, I., Vicari, S., Schiavone, C., Cipollone, F., and Guagnano, M.T. (2023). From NAFLD to MASLD: Definition, Pathophysiological Basis and Cardiovascular Implications. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030883"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"154170","DOI":"10.1016\/j.metabol.2020.154170","article-title":"Complications, morbidity and mortality of nonalcoholic fatty liver disease","volume":"111S","author":"Mantovani","year":"2020","journal-title":"Metabolism"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Notarnicola, M., Tutino, V., De Nunzio, V., Cisternino, A.M., Cofano, M., Donghia, R., Giannuzzi, V., Zappimbulso, M., Milella, R.A., and Giannelli, G. (2024). Daily Orange Consumption Reduces Hepatic Steatosis Prevalence in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Exploratory Outcomes of a Randomized Clinical Trial. Nutrients, 16.","DOI":"10.3390\/nu16183191"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Tatoli, R., Caterina, B., Donghia, R., Pesole, P.L., Fontana, L., and Giannelli, G. (2025). Dietary Omega-3 Fatty Acids from Fish and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease in a Mediterranean Population: Findings from the NUTRIHEP Cohort. Nutrients, 17.","DOI":"10.3390\/nu17213372"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101238","DOI":"10.1016\/j.molmet.2021.101238","article-title":"Metabolic-associated fatty liver disease and lipoprotein metabolism","volume":"50","author":"Heeren","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s43556-025-00321-3","article-title":"Cholesterol metabolism: Molecular mechanisms, biological functions, diseases, and therapeutic targets","volume":"6","author":"Cui","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2005.10.024","article-title":"LDL-cholesterol lowering or HDL-cholesterol raising for cardiovascular prevention. A lesson from cholesterol turnover studies and others","volume":"186","author":"Sirtori","year":"2006","journal-title":"Atherosclerosis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/978-1-0716-2341-1_12","article-title":"Lipidomic Analysis of Extracellular Vesicles Isolated from Human Plasma and Serum","volume":"2504","author":"Sun","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/ansa.202300009","article-title":"Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022","volume":"4","author":"Gehin","year":"2023","journal-title":"Anal. Sci. Adv."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ding, M., and Rexrode, K.M. (2020). A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins. Metabolites, 10.","DOI":"10.3390\/metabo10040163"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hliwa, A., Ramos-Molina, B., Laski, D., Mika, A., and Sledzinski, T. (2021). The Role of Fatty Acids in Non-Alcoholic Fatty Liver Disease Progression: An Update. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136900"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/JIR.S229691","article-title":"Saturated Fatty Acids in Obesity-Associated Inflammation","volume":"13","author":"Zhou","year":"2020","journal-title":"J. Inflamm. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100756","DOI":"10.1016\/j.jhepr.2023.100756","article-title":"Saturated fatty acid-enriched small extracellular vesicles mediate a crosstalk inducing liver inflammation and hepatocyte insulin resistance","volume":"5","author":"Alen","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.3748\/wjg.15.1809","article-title":"Olive oil consumption and non-alcoholic fatty liver disease","volume":"15","author":"Assy","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.lfs.2018.04.049","article-title":"Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance\u2014A review","volume":"203","author":"Saini","year":"2018","journal-title":"Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"127855","DOI":"10.1016\/j.talanta.2025.127855","article-title":"Transformative potentials, challenges and innovative solutions of lipidomics in multiple clinical applications","volume":"291","author":"Malarvannan","year":"2025","journal-title":"Talanta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1743-7075-8-65","article-title":"The intake of high fat diet with different trans fatty acid levels differentially induces oxidative stress and non alcoholic fatty liver disease (NAFLD) in rats","volume":"8","author":"Dhibi","year":"2011","journal-title":"Nutr. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Notarnicola, M., De Nunzio, V., Lippolis, T., Tutino, V., Cisternino, A.M., Iacovazzi, P.A., Milella, R.A., Gasparro, M., Negro, R., and Polignano, M. (2022). Beneficial Effects of Table Grape Use on Serum Levels of Omega-3 Index and Liver Function: A Randomized Controlled Clinical Trial. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092310"},{"key":"ref_21","first-page":"1700","article-title":"Polyphenols and their benefits: A review","volume":"20","author":"Rasouli","year":"2017","journal-title":"Int. J. Food Prop."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lippolis, T., Cofano, M., Caponio, G.R., De Nunzio, V., and Notarnicola, M. (2023). Bioaccessibility and Bioavailability of Diet Polyphenols and Their Modulation of Gut Microbiota. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043813"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tutino, V., Gigante, I., Scavo, M.P., Refolo, M.G., Nunzio, V., Milella, R.A., Caruso, M.G., and Notarnicola, M. (2020). Stearoyl-CoA Desaturase-1 Enzyme Inhibition by Grape Skin Extracts Affects Membrane Fluidity in Human Colon Cancer Cell Lines. Nutrients, 12.","DOI":"10.3390\/nu12030693"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cofano, M., Saponara, I., De Nunzio, V., Pinto, G., Aloisio Caruso, E., Centonze, M., and Notarnicola, M. (2025). Hesperidin Is a Promising Nutraceutical Compound in Counteracting the Progression of NAFLD In Vitro. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26135982"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yan, J., and Fine, J. (2004). Estimating equations for association structures. Stat. Med., 23, 859\u2013874; discussion 857\u2013875, 879\u2013880.","DOI":"10.1002\/sim.1650"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Shults, J., and Hilbe, J. (2014). Quasi-Least Squares Regression, Chapman and Hall\/CRC.","DOI":"10.1201\/b16446"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1159\/000330228","article-title":"An overview of longitudinal data analysis methods for neurological research","volume":"1","author":"Locascio","year":"2011","journal-title":"Dement. Geriatr. Cogn. Dis. Extra"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Shoukri, M.M. (2018). Analysis of Correlated Data with SAS and R, Chapman and Hall\/CRC. [4th ed.].","DOI":"10.1201\/9781315277738"},{"key":"ref_29","unstructured":"Cohen, J. (1988). Statistical Power Analysis for the Behavioral Sciences, Academic Press. [2nd ed.]."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1037\/0003-066X.45.12.1304","article-title":"Things I have learned (so far)","volume":"45","author":"Cohen","year":"1990","journal-title":"Am. Psychol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v015.i02","article-title":"The R Package geepack for Generalized Estimating Equations","volume":"15","author":"Halekoh","year":"2006","journal-title":"J. Stat. Softw."},{"key":"ref_32","first-page":"12","article-title":"Geepack: Yet Another Package for Generalized Estimating Equations","volume":"2","author":"Yan","year":"2002","journal-title":"R-News"},{"key":"ref_33","unstructured":"Harrell, J.R. (2025, April 08). Hmisc: Harrell Miscellaneous. R Package Version 5.2-0. Available online: https:\/\/CRAN.R-project.org\/package=Hmisc."},{"key":"ref_34","unstructured":"Champely, S. (2026, January 09). _pwr: Basic Functions for Power Analysis_. R Package Version 1.3-0. Available online: https:\/\/CRAN.R-project.org\/package=pwr."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_36","unstructured":"Crespi, C.M. (2020). Power and Sample Size in R, Chapman & Hall."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1198\/000313001300339897","article-title":"The Abuse of Power: The Pervasive Fallacy of Power Calculations for Data Analysis","volume":"55","author":"Hoening","year":"2001","journal-title":"Am. Stat."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Saponara, I., Caruso, E.A., Cofano, M., De Nunzio, V., Pinto, G., Centonze, M., and Notarnicola, M. (2025). Anti-Inflammatory and Anti-Fibrotic Effects of a Mixture of Polyphenols Extracted from \u201cNavelina\u201d Orange in Human Hepa-RG and LX-2 Cells Mediated by Cannabinoid Receptor 2. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020512"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zupo, R., Castellana, F., Crupi, P., Desantis, A., Rondanelli, M., Corbo, F., and Clodoveo, M.L. (2023). Olive Oil Polyphenols Improve HDL Cholesterol and Promote Maintenance of Lipid Metabolism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Metabolites, 13.","DOI":"10.3390\/metabo13121187"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rudrapal, M., Rakshit, G., Singh, R.P., Garse, S., Khan, J., and Chakraborty, S. (2024). Dietary Polyphenols: Review on Chemistry\/Sources, Bioavailability\/Metabolism, Antioxidant Effects, and Their Role in Disease Management. Antioxidants, 13.","DOI":"10.3390\/antiox13040429"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"115682","DOI":"10.1016\/j.foodres.2025.115682","article-title":"Plant polyphenols as natural bioactives for alleviating lipid metabolism disorder: Mechanisms and application challenges","volume":"203","author":"Wei","year":"2025","journal-title":"Food Res. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"264","DOI":"10.4103\/hm.HM-D-24-00106","article-title":"Effects of a Diet Rich in Polyphenols on Lipid Metabolism: An Updated Narrative Review","volume":"9","author":"Scavuzzi","year":"2025","journal-title":"Heart Mind"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e0802","DOI":"10.1097\/HC9.0000000000000802","article-title":"Arachidonic acid metabolism in metabolic dysfunction-associated steatotic liver disease and liver fibrosis","volume":"9","author":"Ma","year":"2025","journal-title":"Hepatol. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/j.1365-2125.2012.04374.x","article-title":"Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology?","volume":"75","author":"Calder","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.biopha.2006.07.080","article-title":"Evolutionary aspects of diet, the omega-6\/omega-3 ratio and genetic variation: Nutritional implications for chronic diseases","volume":"60","author":"Simopoulos","year":"2006","journal-title":"Biomed. Pharmacother."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tutino, V., De Nunzio, V., Caruso, M.G., Veronese, N., Lorusso, D., Di Masi, M., Benedetto, M.L., and Notarnicola, M. (2019). Elevated AA\/EPA Ratio Represents an Inflammatory Biomarker in Tumor Tissue of Metastatic Colorectal Cancer Patients. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20082050"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e000385","DOI":"10.1136\/openhrt-2015-000385","article-title":"The importance of a balanced omega-6 to omega-3 ratio in the prevention and management of obesity","volume":"3","author":"Simopoulos","year":"2016","journal-title":"Open Heart"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/ajcn\/85.3.709","article-title":"Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans","volume":"85","author":"Baba","year":"2007","journal-title":"Am. J. Clin. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/8\/1254\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T04:20:50Z","timestamp":1776486050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/8\/1254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["nu18081254"],"URL":"https:\/\/doi.org\/10.3390\/nu18081254","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]}}}