{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:43:05Z","timestamp":1787625785113,"version":"build-2736575974"},"reference-count":129,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"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>Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The dietary imposed dyslipidemia promotes redox imbalance by the generation of excess levels of reactive oxygen species and induces adipocyte dysfunction and reprogramming, leading to a low grade systemic inflammation and ectopic lipid deposition, e.g., in the liver, hereby promoting a vicious circle in which dietary factors initiate a metabolic change that further exacerbates the negative consequences of an adverse life-style. Large epidemiological studies and findings from controlled in vivo animal studies have provided evidence supporting an association between poor vitamin C (VitC) status and propagation of life-style associated diseases. In addition, overweight per se has been shown to result in reduced plasma VitC, and the distribution of body fat in obesity has been shown to have an inverse relationship with VitC plasma levels. Recently, a number of epidemiological studies have indicated a VitC intake below the recommended daily allowance (RDA) in NAFLD-patients, suggesting an association between dietary habits, disease and VitC deficiency. In the general population, VitC deficiency (defined as a plasma concentration below 23 \u03bcM) affects around 10% of adults, however, this prevalence is increased by an adverse life-style, deficiency potentially playing a broader role in disease progression in specific subgroups. This review discusses the currently available data from human surveys and experimental models in search of a putative role of VitC deficiency in the development of NAFLD and NASH.<\/jats:p>","DOI":"10.3390\/nu6125473","type":"journal-article","created":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T02:07:08Z","timestamp":1417486028000},"page":"5473-5499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Does Vitamin C Deficiency Promote Fatty Liver  Disease Development?"],"prefix":"10.3390","volume":"6","author":[{"given":"David","family":"Ipsen","sequence":"first","affiliation":[{"name":"Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences,  University of Copenhagen, Ridebanevej 9, Frederiksberg C, 1870 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernille","family":"Tveden-Nyborg","sequence":"additional","affiliation":[{"name":"Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences,  University of Copenhagen, Ridebanevej 9, Frederiksberg C, 1870 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6514-8407","authenticated-orcid":false,"given":"Jens","family":"Lykkesfeldt","sequence":"additional","affiliation":[{"name":"Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences,  University of Copenhagen, Ridebanevej 9, Frederiksberg C, 1870 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0140-6736(14)60460-8","article-title":"Global, regional, and national prevalence of overweight and obesity in children and adults during 1980\u20132013: A systematic analysis for the global burden of disease study 2013","volume":"384","author":"Ng","year":"2014","journal-title":"Lancet"},{"key":"ref_2","first-page":"4","article-title":"Recent advances in the relationship between obesity, inflammation, and insulin resistance","volume":"17","author":"Bastard","year":"2006","journal-title":"Eur. Cytokine Netw."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.metabol.2014.01.009","article-title":"Differences in the redox status of human visceral and subcutaneous adipose tissues\u2014Relationships to obesity and metabolic risk","volume":"63","author":"Jankovic","year":"2014","journal-title":"Metabolism"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1381\/096089204323093453","article-title":"Changes in leptin, plasminogen activator factor and oxidative stress in morbidly obese patients following open and laparoscopic swedish adjustable gastric banding","volume":"14","author":"Uzun","year":"2004","journal-title":"Obes. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/clpt.2009.311","article-title":"Obesity, inflammation, and cardiovascular risk","volume":"87","author":"Mathieu","year":"2010","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.3748\/wjg.v13.i26.3540","article-title":"Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease","volume":"13","author":"Qureshi","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1002\/hep.24001","article-title":"Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis","volume":"52","author":"Tilg","year":"2010","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1471-230X-5-35","article-title":"Measurement of the total antioxidant response using a novel automated method in subjects with nonalcoholic steatohepatitis","volume":"5","author":"Horoz","year":"2005","journal-title":"BMC Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/ejcn.2012.17","article-title":"Proinflammatory and oxidative stress markers in patients submitted to roux-en-y gastric bypass after 1 year of follow-up","volume":"66","author":"Moreira","year":"2012","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1006\/abbi.1993.1074","article-title":"The pecking order of free radicals and antioxidants: Lipid peroxidation, \u03b1-tocopherol, and ascorbate","volume":"300","author":"Buettner","year":"1993","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1749-6632.1985.tb51167.x","article-title":"Post-translational processing of procollagens","volume":"460","author":"Kivirikko","year":"1985","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1749-6632.1987.tb23758.x","article-title":"Serum levels of vitamin C in relation to dietary and supplemental intake of vitamin C in smokers and nonsmokers","volume":"498","author":"Smith","year":"1987","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1080\/07315724.2001.10719040","article-title":"Relation of serum ascorbic acid to mortality among us adults","volume":"20","author":"Simon","year":"2001","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"870","DOI":"10.2105\/AJPH.94.5.870","article-title":"Vitamin C deficiency and depletion in the United States: The third national health and nutrition examination survey, 1988 to 1994","volume":"94","author":"Hampl","year":"2004","journal-title":"Am. J. Public Health"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1136\/jech.54.5.355","article-title":"Plasma vitamin C and food choice in the third glasgow monica population survey","volume":"54","author":"Wrieden","year":"2000","journal-title":"J. Epidemiol. Commun. Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1017\/S0007114509993229","article-title":"Is vitamin C supplementation beneficial? Lessons learned from randomised controlled trials","volume":"103","author":"Lykkesfeldt","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1080\/10408398.2011.649149","article-title":"Authors\u2019 perspective: What is the optimum intake of vitamin C in humans?","volume":"52","author":"Frei","year":"2012","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1089\/ars.2013.5382","article-title":"Does vitamin C deficiency increase lifestyle-associated vascular disease progression? Evidence based on experimental and clinical studies","volume":"19","author":"Lykkesfeldt","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/ajcn\/87.2.362","article-title":"Vitamin status in morbidly obese patients: A cross-sectional study","volume":"87","author":"Aasheim","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1093\/ajcn\/82.6.1203","article-title":"Plasma ascorbic acid concentrations and fat distribution in 19,068 british men and women in the european prospective investigation into cancer and nutrition norfolk cohort study","volume":"82","author":"Canoy","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1093\/jn\/137.7.1757","article-title":"Plasma vitamin C is inversely related to body mass index and waist circumference but not to plasma adiponectin in nonsmoking adults","volume":"137","author":"Johnston","year":"2007","journal-title":"J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jada.2011.02.003","article-title":"Vitamin C status is related to proinflammatory responses and impaired vascular endothelial function in healthy, college-aged lean and obese men","volume":"111","author":"Mah","year":"2011","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1172\/JCI45887","article-title":"Adipose tissue remodeling and obesity","volume":"121","author":"Sun","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.bpobgyn.2013.02.007","article-title":"Glucose homeostasis, obesity and diabetes","volume":"27","author":"Bano","year":"2013","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1172\/JCI21625","article-title":"Increased oxidative stress in obesity and its impact on metabolic syndrome","volume":"114","author":"Furukawa","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1126\/science.1230721","article-title":"Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis","volume":"339","author":"Odegaard","year":"2013","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/S0140-6736(05)61032-X","article-title":"Type 2 diabetes: Principles of pathogenesis and therapy","volume":"365","author":"Stumvoll","year":"2005","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1097\/01.ASN.0000141966.69934.21","article-title":"The inflammatory syndrome: The role of adipose tissue cytokines in metabolic disorders linked to obesity","volume":"15","author":"Wisse","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1126\/science.1160794","article-title":"A stress signaling pathway in adipose tissue regulates hepatic insulin resistance","volume":"322","author":"Sabio","year":"2008","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1038\/sj.ijo.0802399","article-title":"Adipocyte functions are modulated by cell size change: Potential involvement of an integrin\/erk signalling pathway","volume":"27","author":"Farnier","year":"2003","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"755","DOI":"10.2337\/diabetes.51.3.755","article-title":"Extreme insulin resistance of the central adipose depot in vivo","volume":"51","author":"Mittelman","year":"2002","journal-title":"Diabetes"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35279","DOI":"10.1074\/jbc.M706762200","article-title":"A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via toll-like receptors 2 and 4 and JNK-dependent pathways","volume":"282","author":"Nguyen","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/path.4255","article-title":"Emerging role of oxidative stress in metabolic syndrome and cardiovascular diseases: Important role of rac\/nadph oxidase","volume":"231","author":"Elnakish","year":"2013","journal-title":"J. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.2337\/diabetes.52.9.2346","article-title":"The metabolic syndrome and antioxidant concentrations: Findings from the third national health and nutrition examination survey","volume":"52","author":"Ford","year":"2003","journal-title":"Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/sj.ejcn.1600567","article-title":"Swedish obese subjects (SOS): An obesity intervention study with a nutritional perspective","volume":"52","author":"Lissner","year":"1998","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/ejcn.2013.196","article-title":"Dietary factors associated with subclinical inflammation among girls","volume":"67","author":"Maffeis","year":"2013","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1111\/j.1463-1326.2010.01297.x","article-title":"Synergistic effects of ascorbic acid and thiazolidinedione on secretion of high molecular weight adiponectin from human adipocytes","volume":"12","author":"Rose","year":"2010","journal-title":"Diabetes Obes. Metab."},{"key":"ref_38","first-page":"471","article-title":"Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients","volume":"126","year":"2007","journal-title":"Indian J. Med. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.freeradbiomed.2004.12.010","article-title":"Effects of oxidative stress on adiponectin secretion and lactate production in 3T3-L1 adipocytes","volume":"38","author":"Soares","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/hep.20280","article-title":"Beyond insulin resistance in NASH: TNF-\u03b1 or adiponectin?","volume":"40","author":"Hui","year":"2004","journal-title":"Hepatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1053\/j.gastro.2012.04.001","article-title":"The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the american gastroenterological association, american association for the study of liver diseases, and american college of gastroenterology","volume":"142","author":"Chalasani","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.jhep.2011.08.025","article-title":"The interaction of hepatic lipid and glucose metabolism in liver diseases","volume":"56","author":"Bechmann","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrgastro.2010.191","article-title":"Animal models of nonalcoholic fatty liver disease","volume":"8","author":"Hebbard","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jhep.2004.09.012","article-title":"The histological course of nonalcoholic fatty liver disease: A longitudinal study of 103 patients with sequential liver biopsies","volume":"42","author":"Adams","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/hep.21327","article-title":"Long-term follow-up of patients with NAFLD and elevated liver enzymes","volume":"44","author":"Ekstedt","year":"2006","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1053\/gast.2002.34168","article-title":"Expanding the natural history of nonalcoholic steatohepatitis: From cryptogenic cirrhosis to hepatocellular carcinoma","volume":"123","author":"Bugianesi","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1210\/jc.2004-1024","article-title":"Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease","volume":"90","author":"Angelico","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1053\/jhep.2003.50161","article-title":"Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome","volume":"37","author":"Marchesini","year":"2003","journal-title":"Hepatology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/sj.ijo.0800571","article-title":"Liver abnormalities in severely obese subjects: Effect of drastic weight loss after gastroplasty","volume":"22","author":"Luyckx","year":"1998","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.diabres.2008.11.039","article-title":"Prevalence of non-alcoholic fatty liver disease in urban south indians in relation to different grades of glucose intolerance and metabolic syndrome","volume":"84","author":"Mohan","year":"2009","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.mcna.2007.06.001","article-title":"Nonalcoholic fatty liver disease as a complication of insulin resistance","volume":"91","author":"Abdelmalek","year":"2007","journal-title":"Med. Clin. N. Am."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.3390\/nu5051544","article-title":"Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease","volume":"5","author":"Gaggini","year":"2013","journal-title":"Nutrients"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1172\/JCI23621","article-title":"Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease","volume":"115","author":"Donnelly","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1900\/RDS.2012.9.82","article-title":"Dyslipidemia and diabetes: Reciprocal impact of impaired lipid metabolism and beta-cell dysfunction on micro- and macrovascular complications","volume":"9","author":"Bardini","year":"2012","journal-title":"Rev. Diabet. Stud."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jcme.2008.01.002","article-title":"Vitamin C supplementation lowers serum low-density lipoprotein cholesterol and triglycerides: A meta-analysis of 13 randomized controlled trials","volume":"7","author":"McRae","year":"2008","journal-title":"J. Chiropr. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1136\/gut.2010.214577","article-title":"Anti-inflammatory effects of excessive weight loss: Potent suppression of adipose interleukin 6 and tumour necrosis factor alpha expression","volume":"59","author":"Moschen","year":"2010","journal-title":"Gut"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1053\/j.gastro.2003.08.029","article-title":"Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin","volume":"125","author":"Kamada","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"802","DOI":"10.3748\/wjg.v19.i6.802","article-title":"What is the role of adiponectin in obesity related non-alcoholic fatty liver disease?","volume":"19","author":"Finelli","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1172\/JCI31021","article-title":"Obesity-associated improvements in metabolic profile through expansion of adipose tissue","volume":"117","author":"Kim","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cell.2009.12.052","article-title":"Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing Il-6 and TNF expression","volume":"140","author":"Park","year":"2010","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.clinre.2012.06.005","article-title":"Does fructose consumption contribute to non-alcoholic fatty liver disease?","volume":"36","author":"Tappy","year":"2012","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.jnutbio.2014.01.008","article-title":"Dietary \u03b1-tocopherol and atorvastatin reduce high-fat-induced lipid accumulation and down-regulate cd36 protein in the liver of guinea pigs","volume":"25","author":"Podszun","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"602","DOI":"10.3109\/10715762.2013.806796","article-title":"A high-fat and cholesterol diet causes fatty liver in guinea pigs. The role of iron and oxidative damage","volume":"47","author":"Ye","year":"2013","journal-title":"Free Radic. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1271\/bbb.120722","article-title":"Effect of blueberry feeding on lipids and oxidative stress in the serum, liver and aorta of guinea pigs fed on a high-cholesterol diet","volume":"77","author":"Coban","year":"2013","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"113","DOI":"10.4162\/nrp.2012.6.2.113","article-title":"Lutein decreases oxidative stress and inflammation in liver and eyes of guinea pigs fed a hypercholesterolemic diet","volume":"6","author":"Kim","year":"2012","journal-title":"Nutr. Res. Pract."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.cmet.2006.07.006","article-title":"Mitochondrial free cholesterol loading sensitizes to TNF- and FAS-mediated steatohepatitis","volume":"4","author":"Mari","year":"2006","journal-title":"Cell Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/hep.20283","article-title":"Free fatty acids promote hepatic lipotoxicity by stimulating TNF-\u03b1 expression via a lysosomal pathway","volume":"40","author":"Feldstein","year":"2004","journal-title":"Hepatology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.3748\/wjg.v19.i8.1158","article-title":"From fatty liver to fibrosis: A tale of \u201csecond hit\u201d","volume":"19","author":"Basaranoglu","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1111\/j.1440-1746.2006.04640.x","article-title":"Role of mitochondria in non-alcoholic fatty liver disease","volume":"22","author":"Pessayre","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"E275","DOI":"10.1152\/ajpendo.00644.2005","article-title":"Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells","volume":"291","author":"Wei","year":"2006","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_71","first-page":"2","article-title":"Ezetimibe and atorvastatin ameliorate liver injury in foz\/foz mice with NASH","volume":"26","author":"Larter","year":"2011","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00535-012-0527-x","article-title":"Inflammation and fibrogenesis in steatohepatitis","volume":"47","author":"Fujii","year":"2012","journal-title":"J. Gastroenterol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/hep.20177","article-title":"Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis","volume":"39","author":"Laurent","year":"2004","journal-title":"Hepatology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"149","DOI":"10.5009\/gnl.2012.6.2.149","article-title":"Nash is an inflammatory disorder: Pathogenic, prognostic and therapeutic implications","volume":"6","author":"Farrell","year":"2012","journal-title":"Gut Liver"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.clinbiochem.2010.04.003","article-title":"Oxidative stress is independently associated with non-alcoholic fatty liver disease (NAFLD) in subjects with and without type 2 diabetes","volume":"43","author":"Narasimhan","year":"2010","journal-title":"Clin. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1179\/135100010X12826446921464","article-title":"Vitamin C, resveratrol and lipoic acid actions on isolated rat liver mitochondria: All antioxidants but different","volume":"15","author":"Valdecantos","year":"2010","journal-title":"Redox Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1053\/jhep.2003.50132","article-title":"Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis","volume":"37","author":"Musso","year":"2003","journal-title":"Hepatology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"11","DOI":"10.6061\/clinics\/2013(01)OA03","article-title":"Dietary patterns in brazilian patients with nonalcoholic fatty liver disease: A cross-sectional study","volume":"68","author":"Ferolla","year":"2013","journal-title":"Clinics"},{"key":"ref_79","first-page":"57","article-title":"Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis","volume":"34","author":"Koruk","year":"2004","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1042\/CS20030285","article-title":"Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients","volume":"106","author":"Videla","year":"2004","journal-title":"Clin. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/j.1742-7843.2009.00420.x","article-title":"Role of marginal vitamin C deficiency in atherogenesis: In vivo models and clinical studies","volume":"104","author":"Lykkesfeldt","year":"2009","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_82","first-page":"139","article-title":"Association between hyperlipidemia and hepatic cytochrome p-450 in guinea pigs","volume":"97","author":"Roomi","year":"1997","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S0026-0495(98)90131-7","article-title":"Regulation of apolipoprotein B-containing lipoproteins by vitamin C level and dietary fat saturation in guinea pigs","volume":"47","author":"Montano","year":"1998","journal-title":"Metabolism"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1093\/ajcn\/24.10.1238","article-title":"Lowered cholesterol catabolism in guinea pigs with chronic ascorbic acid deficiency","volume":"24","author":"Ginter","year":"1971","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/j.1749-6632.1975.tb29299.x","article-title":"Ascorbic acid in cholesterol and bile acid metabolism","volume":"258","author":"Ginter","year":"1975","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_86","first-page":"307","article-title":"Effect of vitamin C deficiency and excess on the liver: A histopathological and biochemical study in guinea pigs fed normal or high cholesterol diet","volume":"33","author":"Sharma","year":"1990","journal-title":"Indian J. Pathol. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1017\/S0007114510003077","article-title":"High dietary fat and cholesterol exacerbates chronic vitamin C deficiency in guinea pigs","volume":"105","author":"Birck","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1093\/jn\/117.6.1036","article-title":"Effect of dietary ascorbic acid, cholesterol and PCB on cholesterol concentrations in serum and liver in a rat mutant unable to synthesize ascorbic acid","volume":"117","author":"Horio","year":"1987","journal-title":"J. Nutr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1093\/jn\/120.10.1140","article-title":"Effect of vitamin C depletion on serum cholesterol and lipoprotein levels in ODS (od\/od) rats unable to synthesize ascorbic acid","volume":"120","author":"Uchida","year":"1990","journal-title":"J. Nutr."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/jn\/131.1.10","article-title":"Guinea pigs as models for cholesterol and lipoprotein metabolism","volume":"131","author":"Fernandez","year":"2001","journal-title":"J. Nutr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1248\/bpb.34.1046","article-title":"Hyperlipidemic guinea pig model: Mechanisms of triglyceride metabolism disorder and comparison to rat","volume":"34","author":"Yang","year":"2011","journal-title":"Biol. Pharm. Bull."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0891-5849(94)90108-2","article-title":"Dietary vitamin C decreases endogenous protein oxidative damage, malondialdehyde, and lipid peroxidation and maintains fatty acid unsaturation in the guinea pig liver","volume":"17","author":"Barja","year":"1994","journal-title":"Free Radic. Biol. Med."},{"key":"ref_93","first-page":"209","article-title":"Examination for lipid peroxidation in liver microsomes of guinea pigs as a causal factor in the decrease in the content of cytochrome p-450 due to ascorbic acid deficiency","volume":"75","author":"Mori","year":"1992","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3177\/jnsv.59.489","article-title":"Effects of ascorbic acid deficiency on protein and lipid oxidation in livers from SMP30\/GNL knockout mice","volume":"59","author":"Amano","year":"2013","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1179\/1476830512Y.0000000042","article-title":"Combined vitamin C and E deficiency induces motor defects in gulo(\u2212\/\u2212)\/SVCT2(+\/\u2212) mice","volume":"16","author":"Pierce","year":"2013","journal-title":"Nutr. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.brainres.2010.06.037","article-title":"Low ascorbic acid and increased oxidative stress in gulo(\u2212\/\u2212) mice during development","volume":"1349","author":"Harrison","year":"2010","journal-title":"Brain Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3177\/jnsv.52.28","article-title":"Ascorbic acid deficiency stimulates hepatic expression of inflammatory chemokine, cytokine-induced neutrophil chemoattractant-1, in scurvy-prone ODS rats","volume":"52","author":"Horio","year":"2006","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jhep.2011.05.029","article-title":"The SOD2 C47T polymorphism influences NAFLD fibrosis severity: Evidence from case-control and intra-familial allele association studies","volume":"56","author":"Anstee","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0168-8278(02)00073-9","article-title":"In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases","volume":"37","author":"Seki","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1423-0127-19-26","article-title":"Amelioration of diet-induced nonalcoholic steatohepatitis in rats by Mn-salen complexes via reduction of oxidative stress","volume":"19","author":"Rezazadeh","year":"2012","journal-title":"J. Biomed. Sci."},{"key":"ref_101","first-page":"41","article-title":"Prevention of nonalcoholic steatohepatitis in rats by two manganese-salen complexes","volume":"18","author":"Rezazadeh","year":"2014","journal-title":"Iran. Biomed. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1475-2891-2-9","article-title":"Vitamin C and vitamin E in prevention of nonalcoholic fatty liver disease (NAFLD) in choline deficient diet fed rats","volume":"2","author":"Oliveira","year":"2003","journal-title":"Nutr. J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/0021-9150(75)90024-6","article-title":"Ascorbic acid and glycosaminoglycan and lipid metabolism in guinea pigs fed normal and atherogenic diets","volume":"22","author":"Nambisan","year":"1975","journal-title":"Atherosclerosis"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1093\/ajcn\/81.4.736","article-title":"Vitamins E and C are safe across a broad range of intakes","volume":"81","author":"Hathcock","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_105","unstructured":"The National Academies, and Institute of Medicine (2000). Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids, The National Academies Press."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/S0002-8223(00)00189-9","article-title":"Dietary reference intakes for the antioxidant nutrients: Vitamin C, vitamin E, selenium, and carotenoids","volume":"100","author":"Monsen","year":"2000","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"63s","DOI":"10.1038\/oby.2002.192","article-title":"Dietary intake\u2014How do we measure what people are really eating?","volume":"10","author":"Johnson","year":"2002","journal-title":"Obes. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1111\/jgh.12520","article-title":"Associations between intakes of individual nutrients or whole food groups and non-alcoholic fatty liver disease among korean adults","volume":"29","author":"Han","year":"2014","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/MPG.0b013e318229da1a","article-title":"Correlation of vitamin E, uric acid, and diet composition with histologic features of pediatric NAFLD","volume":"54","author":"Vos","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/ejcn.2010.35","article-title":"Dietary and physical activity patterns in children with fatty liver","volume":"64","author":"Mager","year":"2010","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.jand.2014.01.009","article-title":"A cross-sectional study assessing dietary intake and physical activity in canadian patients with nonalcoholic fatty liver disease vs. healthy controls","volume":"114","author":"Arendt","year":"2014","journal-title":"J. Acad. Nutr. Diet."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1097\/01.mcg.0000212608.59090.08","article-title":"Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD)","volume":"40","author":"Madan","year":"2006","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_113","first-page":"277","article-title":"Clinical, biochemical and histological correlations in a group of non-drinker subjects with non-alcoholic fatty liver disease","volume":"70","author":"Canbakan","year":"2007","journal-title":"Acta Gastro-Enterol. Belgica"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1475-2891-6-41","article-title":"Is plasma vitamin C an appropriate biomarker of vitamin C intake? A systematic review and meta-analysis","volume":"6","author":"Dehghan","year":"2007","journal-title":"Nutr. J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1073\/pnas.93.8.3704","article-title":"Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance","volume":"93","author":"Levine","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ahj.2011.05.007","article-title":"Plasma vitamin C predicts incident heart failure in men and women in european prospective investigation into cancer and nutrition-norfolk prospective study","volume":"162","author":"Pfister","year":"2011","journal-title":"Am. Heart J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1111\/j.1365-2036.2006.03161.x","article-title":"Effect of vitamin E on aminotransferase levels and insulin resistance in children with non-alcoholic fatty liver disease","volume":"24","author":"Nobili","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/hep.22336","article-title":"Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: A randomized, controlled trial","volume":"48","author":"Nobili","year":"2008","journal-title":"Hepatology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1111\/j.1572-0241.2003.08699.x","article-title":"Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis","volume":"98","author":"Harrison","year":"2003","journal-title":"Am. J. Gastroenterol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1016\/j.amjgastroenterol.2003.08.001","article-title":"Vitamins E and C for the treatment of NASH: Duplication of results but lack of demonstration of efficacy","volume":"98","author":"Adams","year":"2003","journal-title":"Am. J. Gastroenterol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1542\/peds.113.S3.1097","article-title":"Liver","volume":"113","year":"2004","journal-title":"Pediatrics"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.clnu.2007.02.002","article-title":"Update on non-alcoholic fatty liver disease in children","volume":"26","author":"Papandreou","year":"2007","journal-title":"Clin. Nutr."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2147\/HMER.S41258","article-title":"Treatment of nonalcoholic steatohepatitis with vitamins E and C: A pilot study","volume":"5","author":"Kawanaka","year":"2013","journal-title":"Hepat. Med."},{"key":"ref_124","first-page":"124","article-title":"Management of fatty liver disease with vitamin E and C compared to ursodeoxycholic acid treatment","volume":"16","author":"Gunsar","year":"2005","journal-title":"Turkish J. Gastroenterol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/ajg.2010.299","article-title":"Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: The St. Francis Heart Study randomized clinical trial","volume":"106","author":"Foster","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1038\/oby.2008.64","article-title":"Nash predicts plasma inflammatory biomarkers independently of visceral fat in men","volume":"16","author":"Targher","year":"2008","journal-title":"Obesity"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1002\/hep.23593","article-title":"Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: The framingham heart study","volume":"51","author":"Speliotes","year":"2010","journal-title":"Hepatology"},{"key":"ref_128","first-page":"131","article-title":"Efficacy of omega-3 fatty acids, atorvastatin and orlistat in non-alcoholic fatty liver disease with dyslipidemia","volume":"23","author":"Hatzitolios","year":"2004","journal-title":"Indian J. Gastroenterol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1053\/gast.2002.35354","article-title":"The utility of radiological imaging in nonalcoholic fatty liver disease","volume":"123","author":"Saadeh","year":"2002","journal-title":"Gastroenterology"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/6\/12\/5473\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:10:12Z","timestamp":1760217012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/6\/12\/5473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,1]]},"references-count":129,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2014,12]]}},"alternative-id":["nu6125473"],"URL":"https:\/\/doi.org\/10.3390\/nu6125473","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,1]]}}}