{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:32:03Z","timestamp":1791873123145,"version":"4.3.4"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although the symptoms are absent or poorly expressed in most cases, some patients may progress to end-stage liver disease. The pathogenesis of NAFLD is known to be multifactorial. Current therapeutic recommendations focus on lifestyle changes in order to reduce the incidence of risk factors and drugs targeting major molecular pathways potentially involved in the development of this disease. Given that a pharmacological treatment, completely safe and effective, is not currently known in recent years more research has been done on the effects that some bio-active natural compounds, derived from plants, have in preventing the onset and progression of NAFLD. Numerous studies, in animals and humans, have shown that phytosterols (PSs) play an important role in this pathology. Phytosterols are natural products that are found naturally in plant. More than 250 phytosterols have been identified, but the most common in the diet are stigmasterol, \u03b2-sitosterol, and campesterol. Consumption of dietary PSs can reduce serum cholesterol levels. Due to these properties, most studies have focused on their action on lipid metabolism and the evolution of NAFLD. PSs may reduce steatosis, cytotoxicity oxidative stress, inflammation, and apoptosis. The purpose of this review is to provide an overview of the importance of dietary phytosterols, which are a window of opportunity in the therapeutic management of NAFLD.<\/jats:p>","DOI":"10.3390\/nu14112187","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:14:14Z","timestamp":1653437654000},"page":"2187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["The Role of Phytosterols in Nonalcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5836-1517","authenticated-orcid":false,"given":"Otilia","family":"Frasinariu","sequence":"first","affiliation":[{"name":"Department of Mother and Child, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Serban","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Mihaela","family":"Trandafir","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9825-6711","authenticated-orcid":false,"given":"Ingrith","family":"Miron","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3937-7425","authenticated-orcid":false,"given":"Magdalena","family":"Starcea","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Vasiliu","sequence":"additional","affiliation":[{"name":"Department of Physiology, \u201cGrigore T. 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Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tarantino, G., Citro, V., and Capone, D. (2019). Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010015"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease","volume":"158","author":"Eslam","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/S2468-1253(21)00183-7","article-title":"Defining paediatric metabolic (dysfunction)-associated fatty liver disease: An international expert consensus statement","volume":"6","author":"Eslam","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Flisiak-Jackiewicz, M., Bobrus-Chociej, A., Wasilewska, N., and Lebensztejn, D. (2021). From Nonalcoholic Fatty Liver Disease (NAFLD) to Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)\u2014New Terminology in Pediatric Patients as a Step in Good Scientific Direction?. J. Clin. Med., 10.","DOI":"10.20944\/preprints202101.0516.v1"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Drescher, H.K., Weiskirchen, S., and Weiskirchen, R. (2019). Current Status in Testing for Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH). Cells, 8.","DOI":"10.3390\/cells8080845"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1002\/hep.30251","article-title":"Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis","volume":"69","author":"Younossi","year":"2019","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Anderson, E.L., Howe, L., Jones, H., Higgins, J., Lawlor, D.A., and Fraser, A. (2015). The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140908"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/S0016-5085(98)70599-2","article-title":"Steatohepatitis: A tale of two \u201chits\u201d?","volume":"114","author":"Day","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1007\/s13238-017-0436-0","article-title":"New insight into inter-organ crosstalk contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"9","author":"Zhang","year":"2017","journal-title":"Protein Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.3748\/wjg.v24.i27.2974","article-title":"Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From \u201ctwo hit theory\u201d to \u201cmultiple hit model\u201d","volume":"24","author":"Fang","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"26087","DOI":"10.3390\/ijms161125942","article-title":"The Role of Oxidative Stress and Antioxidants in Liver Diseases","volume":"16","author":"Li","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S1499-3872(13)60021-1","article-title":"Therapeutic approaches to non-alcoholic fatty liver disease: Past achievements and future challenges","volume":"12","author":"Xiao","year":"2013","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"53","DOI":"10.21037\/tgh.2019.06.06","article-title":"Emerging medical therapies for non-alcoholic fatty liver disease and for alcoholic hepatitis","volume":"4","author":"Wong","year":"2019","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.nut.2011.11.017","article-title":"Non-alcoholic fatty liver disease in children now: Lifestyle changes and pharmacologic treatments","volume":"28","author":"Alisi","year":"2012","journal-title":"Nutrition"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/hep.25762","article-title":"The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association","volume":"55","author":"Chalasani","year":"2012","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.jhep.2010.04.008","article-title":"A position statement on NAFLD\/NASH based on the EASL 2009 special conference","volume":"53","author":"Ratziu","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105517","DOI":"10.1016\/j.phrs.2021.105517","article-title":"Current innovations in nutraceuticals and functional foods for intervention of non-alcoholic fatty liver disease","volume":"166","author":"Zhao","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/hep.22009","article-title":"Behavior therapy for nonalcoholic fatty liver disease: The need for a multidisciplinary approach","volume":"47","author":"Bellentani","year":"2007","journal-title":"Hepatology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Berardo, C., Di Pasqua, L.G., Cagna, M., Richelmi, P., Vairetti, M., and Ferrigno, A. (2020). Nonalcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis: Current Issues and Future Perspectives in Preclinical and Clinical Research. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249646"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Salvoza, N., Giraudi, P.J., Tiribelli, C., and Rosso, N. (2022). Natural Compounds for Counteracting Nonalcoholic Fatty Liver Disease (NAFLD): Advantages and Limitations of the Suggested Candidates. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052764"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"697","DOI":"10.5740\/jaoacint.SGEPlat","article-title":"Mechanisms Underlying the Health Benefits of Plant Sterol and Stanol Ester Consumption","volume":"98","author":"Plat","year":"2015","journal-title":"J. AOAC Int."},{"key":"ref_25","first-page":"10","article-title":"A review on dietary phytosterols: Their occurrence, metabolism and health benefits","volume":"5","author":"Ogbe","year":"2015","journal-title":"Asian J. Plant Sci. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, X., Xin, Y., Mo, Y., Marozik, P., He, T., and Guo, H. (2022). The Bioavailability and Biological Activities of Phytosterols as Modulators of Cholesterol Metabolism. Molecules, 27.","DOI":"10.3390\/molecules27020523"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"599959","DOI":"10.3389\/fphar.2020.599959","article-title":"Phytosterols: From Preclinical Evidence to Potential Clinical Applications","volume":"11","author":"Salehi","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1016\/j.bbamem.2014.03.019","article-title":"A comparative calorimetric study of the effects of cholesterol and the plant sterols campesterol and brassicasterol on the thermotropic phase behavior of dipalmitoylphosphatidylcholine bilayer membranes","volume":"1838","author":"Benesch","year":"2014","journal-title":"Biochim. et Biophys. Acta (BBA)-Biomembr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"127430","DOI":"10.1016\/j.foodchem.2020.127430","article-title":"Formation of phytosterol photooxidation products: A chemical reaction mechanism for light-induced oxidation","volume":"333","author":"Yang","year":"2020","journal-title":"Food Chem."},{"key":"ref_30","first-page":"2259","article-title":"Stigmasterol: A Comprehensive Review","volume":"2","author":"Kaur","year":"2011","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"110702","DOI":"10.1016\/j.biopha.2020.110702","article-title":"An update on \u03b2-sitosterol: A potential herbal nutraceutical for diabetic management","volume":"131","author":"Babu","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_32","first-page":"475","article-title":"Phytosterols in the Treatment of Hypercholesterolemia and Prevention of Cardiovascular Diseases","volume":"109","author":"Cabral","year":"2017","journal-title":"Arq. Bras. de Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Thomas, A. (2000). Fats and Fatty Oils. Ullmann\u2019s Encycl. Ind. Chem.","DOI":"10.1002\/14356007.a10_173"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chen, J., Li, D., Tang, G., Zhou, J., Liu, W., and Bi, Y. (2020). Thermal-Oxidation Stability of Soybean Germ Phytosterols in Different Lipid Matrixes. Molecules, 25.","DOI":"10.3390\/molecules25184079"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1681\/ASN.2006091006","article-title":"Lipoprotein Metabolism and Lipid Management in Chronic Kidney Disease","volume":"18","author":"Kwan","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Poli, A., Marangoni, F., Corsini, A., Manzato, E., Marrocco, W., Martini, D., Medea, G., and Visioli, F. (2021). Phytosterols, Cholesterol Control, and Cardiovascular Disease. Nutrients, 13.","DOI":"10.3390\/nu13082810"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"767","DOI":"10.3389\/fphys.2020.00767","article-title":"The Emerging Role of Hepatocellular eNOS in Non-alcoholic Fatty Liver Disease Development","volume":"11","author":"Cunningham","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.37358\/RC.18.10.6649","article-title":"The Effects of Two Nitric Oxide Donors in Acute Inflammation in Rats Experimental data","volume":"69","author":"Buca","year":"2018","journal-title":"Rev. Chim."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Plat, J., Hendrikx, T., Bieghs, V., Jeurissen, M.L.J., Walenbergh, S.M.A., Van Gorp, P.J., De Smet, E., Konings, M., Vreugdenhil, A.C.E., and Guichot, Y.D. (2014). Protective Role of Plant Sterol and Stanol Esters in Liver Inflammation: Insights from Mice and Humans. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110758"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jff.2014.12.046","article-title":"Flaxseed oil containing flaxseed oil ester of plant sterol attenuates high-fat diet-induced hepatic steatosis in apolipoprotein-E knockout mice","volume":"13","author":"Han","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"srep41604","DOI":"10.1038\/srep41604","article-title":"Phytosterol esters attenuate hepatic steatosis in rats with non-alcoholic fatty liver disease rats fed a high-fat diet","volume":"7","author":"Song","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1039\/C9FO01570A","article-title":"The regulatory effects of phytosterol esters (PSEs) on gut flora and faecal metabolites in rats with NAFLD","volume":"11","author":"Song","year":"2019","journal-title":"Food Funct."},{"key":"ref_43","first-page":"1274","article-title":"Intake of stigmasterol and \u03b2-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet","volume":"1863","author":"Feng","year":"2018","journal-title":"Biochim. et Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1021\/acs.jafc.7b06146","article-title":"Effects of Stigmasterol and \u03b2-Sitosterol on Nonalcoholic Fatty Liver Disease in a Mouse Model: A Lipidomic Analysis","volume":"66","author":"Feng","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1139\/cjpp-2019-0295","article-title":"\u03b2-Sitosterol mitigates the development of high-fructose diet-induced nonalcoholic fatty liver disease in growing male Sprague\u2013Dawley rats","volume":"98","author":"Gumede","year":"2020","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1089\/jmf.2019.0120","article-title":"\u03b2-Sitosterol Shows Potential to Protect Against the Development of High-Fructose Diet-Induced Metabolic Dysfunction in Female Rats","volume":"23","author":"Gumede","year":"2020","journal-title":"J. Med. Food"},{"key":"ref_47","first-page":"1","article-title":"Plant Sterol Ester of \u03b1-Linolenic Acid Attenuates Nonalcoholic Fatty Liver Disease by Rescuing the Adaption to Endoplasmic Reticulum Stress and Enhancing Mitochondrial Biogenesis","volume":"2019","author":"Han","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1080\/07315724.2018.1466739","article-title":"Effects of Phytosterol Supplementation on Serum Levels of Lipid Profiles, Liver Enzymes, Inflammatory Markers, Adiponectin, and Leptin in Patients Affected by Nonalcoholic Fatty Liver Disease: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial","volume":"37","author":"Shahi","year":"2018","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jff.2014.12.025","article-title":"Phytosterols increase circulating endothelial progenitor cells and insulin-like growth factor-1 levels in patients with nonalcoholic fatty liver disease: A randomized crossover study","volume":"13","author":"Chen","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1017\/S0007114520000495","article-title":"Combined effect of n-3 fatty acids and phytosterol esters on alleviating hepatic steatosis in non-alcoholic fatty liver disease subjects: A double-blind placebo-controlled clinical trial","volume":"123","author":"Song","year":"2020","journal-title":"Br. J. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.atherosclerosis.2016.01.035","article-title":"Effects of phytosterols on markers of inflammation: A systematic review and meta-analysis","volume":"248","author":"Rocha","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"BSR2017127","DOI":"10.1042\/BSR20171274","article-title":"Serum, liver and bile sitosterol and sitostanol in obese patients with and without NAFLD","volume":"38","author":"Tauriainen","year":"2018","journal-title":"Biosci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"BSR20180505","DOI":"10.1042\/BSR20180505","article-title":"Comment on Tauriainen et al.: Serum, liver and bile sitosterol and sitostanol in obese patients with and without NAFLD","volume":"38","author":"Plat","year":"2018","journal-title":"Biosci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1039\/D1FO03921K","article-title":"Changes in the serum metabolomic profiles of subjects with NAFLD in response to n-3 PUFAs and phytosterol ester: A double-blind randomized controlled trial","volume":"13","author":"Ding","year":"2022","journal-title":"Food Funct."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/11\/2187\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:17:50Z","timestamp":1760138270000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/11\/2187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,24]]},"references-count":54,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["nu14112187"],"URL":"https:\/\/doi.org\/10.3390\/nu14112187","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,24]]}}}