Micronutrients in Nonalcoholic Fatty Liver Disease Pathogenesis

Octavia Pickett-Blakely, Kimberly Young, Rotonya M Carr, Octavia Pickett-Blakely, Kimberly Young, Rotonya M Carr

Abstract

Micronutrients include electrolytes, minerals, vitamins, and carotenoids, and are required in microgram or milligram quantities for cellular metabolism. The liver plays an important role in micronutrient metabolism and this metabolism often is altered in chronic liver diseases. Here, we review how the liver contributes to micronutrient metabolism; how impaired micronutrient metabolism may be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a systemic disorder of energy, glucose, and lipid homeostasis; and how insights gained from micronutrient biology have informed NAFLD therapeutics. Finally, we highlight some of the challenges and opportunities that remain with investigating the contribution of micronutrients to NAFLD pathology and suggest strategies to incorporate our understanding into the care of NAFLD patients.

Keywords: ALT, alanine aminotransferase; BMI, body mass index; FXR, farnesoid X receptor; IL, interleukin; Micronutrients; NAFLD; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; Obesity; ROS, reactive oxygen species; TGF, transforming growth factor; Vitamins; carotenoids; minerals.

Figures

Figure 1
Figure 1
Micronutrients and the liver in NAFLD. Hepatic contribution to metabolism of the micronutrients involved in NAFLD pathogenesis. Vit., vitamin.

References

    1. Carr R.M., Oranu A., Khungar V. Nonalcoholic fatty liver disease: pathophysiology and management. Gastroenterol Clin North Am. 2016;45:639–652.
    1. Speliotes E.K., Yerges-Armstrong L.M., Wu J., Hernaez R., Kim L.J., Palmer C.D., Gudnason V., Eiriksdottir G., Garcia M.E., Launer L.J., Nalls M.A., Clark J.M., Mitchell B.D., Shuldiner A.R., Butler J.L., Tomas M., Hoffmann U., Hwang S.J., Massaro J.M., O'Donnell C.J., Sahani D.V., Salomaa V., Schadt E.E., Schwartz S.M., Siscovick D.S., Voight B.F., Carr J.J., Feitosa M.F., Harris T.B., Fox C.S., Smith A.V., Kao W.H., Hirschhorn J.N., Borecki I.B. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7 e1001324.
    1. Romeo S., Kozlitina J., Xing C., Pertsemlidis A., Cox D., Pennacchio L.A., Boerwinkle E., Cohen J.C., Hobbs H.H. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–1465.
    1. Abul-Husn N.S., Cheng X., Li A.H., Xin Y., Schurmann C., Stevis P., Liu Y., Kozlitina J., Stender S., Wood G.C., Stepanchick A.N., Still M.D., McCarthy S., O'Dushlaine C., Packer J.S., Balasubramanian S., Gosalia N., Esopi D., Kim S.Y., Mukherjee S., Lopez A.E., Fuller E.D., Penn J., Chu X., Luo J.Z., Mirshahi U.L., Carey D.J., Still C.D., Feldman M.D., Small A., Damrauer S.M., Rader D.J., Zambrowicz B., Olson W., Murphy A.J., Borecki I.B., Shuldiner A.R., Reid J.G., Overton J.D., Yancopoulos G.D., Hobbs H.H., Cohen J.C., Gottesman O., Teslovich T.M., Baras A., Mirshahi T., Gromada J., Dewey F.E. A protein-truncating HSD17B13 variant and protection from chronic liver disease. N Engl J Med. 2018;378:1096–1106.
    1. Browning J.D., Szczepaniak L.S., Dobbins R., Nuremberg P., Horton J.D., Cohen J.C., Grundy S.M., Hobbs H.H. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395.
    1. Williams C.D., Stengel J., Asike M.I., Torres D.M., Shaw J., Contreras M., Landt C.L., Harrison S.A. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140:124–131.
    1. Hales C.M., Fryar C.D., Carroll M.D., Freedman D.S., Ogden C.L. Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007-2008 to 2015-2016. JAMA. 2018;319:1723–1725.
    1. Margariti E., Deutsch M., Manolakopoulos S., Papatheodoridis G.V. Non-alcoholic fatty liver disease may develop in individuals with normal body mass index. Ann Gastroenterol. 2012;25:45–51.
    1. Hagstrom H., Nasr P., Ekstedt M., Hammar U., Stal P., Hultcrantz R., Kechagias S. Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease: long-term follow-up study. Hepatol Commun. 2018;2:48–57.
    1. Wei J.L., Leung J.C., Loong T.C., Wong G.L., Yeung D.K., Chan R.S., Chan H.L., Chim A.M., Woo J., Chu W.C., Wong V.W. Prevalence and severity of nonalcoholic fatty liver disease in non-obese patients: a population study using proton-magnetic resonance spectroscopy. Am J Gastroenterol. 2015;110:1306–1314. quiz 1315.
    1. Bril F., Portillo-Sanchez P., Liu I.C., Kalavalapalli S., Dayton K., Cusi K. Clinical and histologic characterization of nonalcoholic steatohepatitis in African American patients. Diabetes Care. 2018;41:187–192.
    1. Foster T., Anania F.A., Li D., Katz R., Budoff M. The prevalence and clinical correlates of nonalcoholic fatty liver disease (NAFLD) in African Americans: the multiethnic study of atherosclerosis (MESA) Dig Dis Sci. 2013;58:2392–2398.
    1. Zhou X., Han D., Xu R., Li S., Wu H., Qu C., Wang F., Wang X., Zhao Y. A model of metabolic syndrome and related diseases with intestinal endotoxemia in rats fed a high fat and high sucrose diet. PLoS One. 2014;9:e115148.
    1. Bergheim I., Weber S., Vos M., Kramer S., Volynets V., Kaserouni S., McClain C.J., Bischoff S.C. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J Hepatol. 2008;48:983–992.
    1. Henao-Mejia J., Elinav E., Jin C., Hao L., Mehal W.Z., Strowig T., Thaiss C.A., Kau A.L., Eisenbarth S.C., Jurczak M.J., Camporez J.P., Shulman G.I., Gordon J.I., Hoffman H.M., Flavell R.A. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482:179–185.
    1. Spruss A., Kanuri G., Wagnerberger S., Haub S., Bischoff S.C., Bergheim I. Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology. 2009;50:1094–1104.
    1. Ye D., Li F.Y., Lam K.S., Li H., Jia W., Wang Y., Man K., Lo C.M., Li X., Xu A. Toll-like receptor-4 mediates obesity-induced non-alcoholic steatohepatitis through activation of X-box binding protein-1 in mice. Gut. 2012;61:1058–1067.
    1. Sharifnia T., Antoun J., Verriere T.G., Suarez G., Wattacheril J., Wilson K.T., Peek R.M., Jr., Abumrad N.N., Flynn C.R. Hepatic TLR4 signaling in obese NAFLD. Am J Physiol Gastrointest Liver Physiol. 2015;309:G270–G278.
    1. Marra F., Bertolani C. Adipokines in liver diseases. Hepatology. 2009;50:957–969.
    1. Garcia O.P., Long K.Z., Rosado J.L. Impact of micronutrient deficiencies on obesity. Nutr Rev. 2009;67:559–572.
    1. Gernand A.D., Schulze K.J., Stewart C.P., West K.P., Jr., Christian P. Micronutrient deficiencies in pregnancy worldwide: health effects and prevention. Nat Rev Endocrinol. 2016;12:274–289.
    1. Joint FAO/WHO Expert Consultation on Human Vitamin and Mineral Requirements and World Health Organization. Department of Nutrition for Health and Development. Vitamin and mineral requirements in human nutrition. 2nd ed. World Health Organization; Geneva: 2005.
    1. Shenkin A. The key role of micronutrients. Clin Nutr. 2006;25:1–13.
    1. Choi Y., Lee J.E., Chang Y., Kim M.K., Sung E., Shin H., Ryu S. Dietary sodium and potassium intake in relation to non-alcoholic fatty liver disease. Br J Nutr. 2016;116:1447–1456.
    1. Kwok R.M., Torres D.M., Harrison S.A. Vitamin D and nonalcoholic fatty liver disease (NAFLD): is it more than just an association? Hepatology. 2013;58:1166–1174.
    1. Dudek SG. Nutrition essentials for nursing practice. Philadelphia, PA, Lippincott Williams & Wilkins, Wolters Kluwer.
    1. Sies H., Stahl W., Sundquist A.R. Antioxidant functions of vitamins. Vitamins E and C, beta-carotene, and other carotenoids. Ann N Y Acad Sci. 1992;669:7–20.
    1. Chen G., Ni Y., Nagata N., Xu L., Ota T. Micronutrient antioxidants and nonalcoholic fatty liver disease. Int J Mol Sci. 2016;17
    1. Fat-soluble vitamins and micronutrients: Vitamins A and E and carotenoids. Available from: . Accessed July 3, 2018.
    1. Tang G. Bioconversion of dietary provitamin A carotenoids to vitamin A in humans. Am J Clin Nutr. 2010;91:1468S–1473S.
    1. Tang G., Qin J., Dolnikowski G.G., Russell R.M. Short-term (intestinal) and long-term (postintestinal) conversion of beta-carotene to retinol in adults as assessed by a stable-isotope reference method. Am J Clin Nutr. 2003;78:259–266.
    1. Blomhoff R., Green M.H., Berg T., Norum K.R. Transport and storage of vitamin A. Science. 1990;250:399–404.
    1. Saeed A., Dullaart R.P.F., Schreuder T., Blokzijl H., Faber K.N. Disturbed vitamin A metabolism in non-alcoholic fatty liver disease (NAFLD) Nutrients. 2017;10
    1. Hendriks H.F., Verhoofstad W.A., Brouwer A., de Leeuw A.M., Knook D.L. Perisinusoidal fat-storing cells are the main vitamin A storage sites in rat liver. Exp Cell Res. 1985;160:138–149.
    1. Blindauer C.A., Harvey I., Bunyan K.E., Stewart A.J., Sleep D., Harrison D.J., Berezenko S., Sadler P.J. Structure, properties, and engineering of the major zinc binding site on human albumin. J Biol Chem. 2009;284:23116–23124.
    1. Nagamine T., Nakajima K. Significance of metallothionein expression in liver disease. Curr Pharm Biotechnol. 2013;14:420–426.
    1. Carr R.M., Reid A.E. FXR agonists as therapeutic agents for non-alcoholic fatty liver disease. Curr Atheroscler Rep. 2015;17:500.
    1. Schmidt D.R., Holmstrom S.R., Fon Tacer K., Bookout A.L., Kliewer S.A., Mangelsdorf D.J. Regulation of bile acid synthesis by fat-soluble vitamins A and D. J Biol Chem. 2010;285:14486–14494.
    1. Fuchs M., Sanyal A.J. Lipotoxicity in NASH. J Hepatol. 2012;56:291–293.
    1. Hirsova P., Gores G.J. Death receptor-mediated cell death and proinflammatory signaling in nonalcoholic steatohepatitis. Cell Mol Gastroenterol Hepatol. 2015;1:17–27.
    1. de Luis D.A., Pacheco D., Izaola O., Terroba M.C., Cuellar L., Cabezas G. Micronutrient status in morbidly obese women before bariatric surgery. Surg Obes Relat Dis. 2013;9:323–327.
    1. Toh S.Y., Zarshenas N., Jorgensen J. Prevalence of nutrient deficiencies in bariatric patients. Nutrition. 2009;25:1150–1156.
    1. Sanchez A., Rojas P., Basfi-Fer K., Carrasco F., Inostroza J., Codoceo J., Valencia A., Papapietro K., Csendes A., Ruz M. Micronutrient deficiencies in morbidly obese women prior to bariatric surgery. Obes Surg. 2016;26:361–368.
    1. Li J., Cordero P., Nguyen V., Oben J.A. The role of vitamins in the pathogenesis of non-alcoholic fatty liver disease. Integr Med Insights. 2016;11:19–25.
    1. Liu Y., Chen H., Wang J., Zhou W., Sun R., Xia M. Association of serum retinoic acid with hepatic steatosis and liver injury in nonalcoholic fatty liver disease. Am J Clin Nutr. 2015;102:130–137.
    1. Cao H. Adipocytokines in obesity and metabolic disease. J Endocrinol. 2014;220:T47–T59.
    1. de Oliveira C., de Mattos A.B., Silva C.B., Mota J.F., Zemdegs J.C. Nutritional and hormonal modulation of adiponectin and its receptors adipoR1 and adipoR2. Vitam Horm. 2012;90:57–94.
    1. Landrier J.F., Gouranton E., El Yazidi C., Malezet C., Balaguer P., Borel P., Amiot M.J. Adiponectin expression is induced by vitamin E via a peroxisome proliferator-activated receptor gamma-dependent mechanism. Endocrinology. 2009;150:5318–5325.
    1. Zolfaghari H., Askari G., Siassi F., Feizi A., Sotoudeh G. Intake of nutrients, fiber, and sugar in patients with nonalcoholic fatty liver disease in comparison to healthy individuals. Int J Prev Med. 2016;7:98.
    1. Toshimitsu K., Matsuura B., Ohkubo I., Niiya T., Furukawa S., Hiasa Y., Kawamura M., Ebihara K., Onji M. Dietary habits and nutrient intake in non-alcoholic steatohepatitis. Nutrition. 2007;23:46–52.
    1. Da Silva H.E., Arendt B.M., Noureldin S.A., Therapondos G., Guindi M., Allard J.P. A cross-sectional study assessing dietary intake and physical activity in Canadian patients with nonalcoholic fatty liver disease vs healthy controls. J Acad Nutr Diet. 2014;114:1181–1194.
    1. Chen M.D., Lin P.Y. Zinc-induced hyperleptinemia relates to the amelioration of sucrose-induced obesity with zinc repletion. Obes Res. 2000;8:525–529.
    1. Kennedy M.L., Failla M.L., Smith J.C., Jr. Influence of genetic obesity on tissue concentrations of zinc, copper, manganese and iron in mice. J Nutr. 1986;116:1432–1441.
    1. Jayawardena R., Ranasinghe P., Galappatthy P., Malkanthi R., Constantine G., Katulanda P. Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr. 2012;4:13.
    1. Brand I.A., Kleineke J. Intracellular zinc movement and its effect on the carbohydrate metabolism of isolated rat hepatocytes. J Biol Chem. 1996;271:1941–1949.
    1. Carr R.M., Correnti J. Insulin resistance in clinical and experimental alcoholic liver disease. Ann N Y Acad Sci. 2015;1353:1–20.
    1. Kang X., Zhong W., Liu J., Song Z., McClain C.J., Kang Y.J., Zhou Z. Zinc supplementation reverses alcohol-induced steatosis in mice through reactivating hepatocyte nuclear factor-4alpha and peroxisome proliferator-activated receptor-alpha. Hepatology. 2009;50:1241–1250.
    1. Mousavi S.N., Faghihi A., Motaghinejad M., Shiasi M., Imanparast F., Amiri H.L., Shidfar F. Zinc and selenium co-supplementation reduces some lipid peroxidation and angiogenesis markers in a rat model of NAFLD-fed high fat diet. Biol Trace Elem Res. 2018;181:288–295.
    1. Riggio O., Merli M., Capocaccia L., Caschera M., Zullo A., Pinto G., Gaudio E., Franchitto A., Spagnoli R., D'Aquilino E., Seri S., Moretti R., Cantafora A. Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis. Hepatology. 1992;16:785–789.
    1. Aigner E., Strasser M., Haufe H., Sonnweber T., Hohla F., Stadlmayr A., Solioz M., Tilg H., Patsch W., Weiss G., Stickel F., Datz C. A role for low hepatic copper concentrations in nonalcoholic fatty liver disease. Am J Gastroenterol. 2010;105:1978–1985.
    1. Aigner E., Theurl I., Haufe H., Seifert M., Hohla F., Scharinger L., Stickel F., Mourlane F., Weiss G., Datz C. Copper availability contributes to iron perturbations in human nonalcoholic fatty liver disease. Gastroenterology. 2008;135:680–688.
    1. Nobili V., Siotto M., Bedogni G., Rava L., Pietrobattista A., Panera N., Alisi A., Squitti R. Levels of serum ceruloplasmin associate with pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2013;56:370–375.
    1. Antonucci L., Porcu C., Iannucci G., Balsano C., Barbaro B. Non-alcoholic fatty liver disease and nutritional implications: special focus on copper. Nutrients. 2017;9
    1. Lai C.C., Huang W.H., Klevay L.M., Gunning W.T., 3rd, Chiu T.H. Antioxidant enzyme gene transcription in copper-deficient rat liver. Free Radic Biol Med. 1996;21:233–240.
    1. Lai C.C., Huang W.H., Askari A., Wang Y., Sarvazyan N., Klevay L.M., Chiu T.H. Differential regulation of superoxide dismutase in copper-deficient rat organs. Free Radic Biol Med. 1994;16:613–620.
    1. al-Othman A.A., Rosenstein F., Lei K.Y. Copper deficiency increases in vivo hepatic synthesis of fatty acids, triacylglycerols, and phospholipids in rats. Proc Soc Exp Biol Med. 1993;204:97–103.
    1. Fields M., Holbrook J., Scholfield D., Smith J.C., Jr., Reiser S. Effect of fructose or starch on copper-67 absorption and excretion by the rat. J Nutr. 1986;116:625–632.
    1. Church S.J., Begley P., Kureishy N., McHarg S., Bishop P.N., Bechtold D.A., Unwin R.D., Cooper G.J. Deficient copper concentrations in dried-defatted hepatic tissue from ob/ob mice: a potential model for study of defective copper regulation in metabolic liver disease. Biochem Biophys Res Commun. 2015;460:549–554.
    1. Britton L.J., Subramaniam V.N., Crawford D.H. Iron and non-alcoholic fatty liver disease. World J Gastroenterol. 2016;22:8112–8122.
    1. MacDonald G.A., Bridle K.R., Ward P.J., Walker N.I., Houglum K., George D.K., Smith J.L., Powell L.W., Crawford D.H., Ramm G.A. Lipid peroxidation in hepatic steatosis in humans is associated with hepatic fibrosis and occurs predominately in acinar zone 3. J Gastroenterol Hepatol. 2001;16:599–606.
    1. Ryan J.D., Armitage A.E., Cobbold J.F., Banerjee R., Borsani O., Dongiovanni P., Neubauer S., Morovat R., Wang L.M., Pasricha S.R., Fargion S., Collier J., Barnes E., Drakesmith H., Valenti L., Pavlides M. Hepatic iron is the major determinant of serum ferritin in NAFLD patients. Liver Int. 2018;38:164–173.
    1. Kowdley K.V., Belt P., Wilson L.A., Yeh M.M., Neuschwander-Tetri B.A., Chalasani N., Sanyal A.J., Nelson J.E. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2012;55:77–85.
    1. Britton L., Jaskowski L.A., Bridle K., Secondes E., Wallace D., Santrampurwala N., Reiling J., Miller G., Mangiafico S., Andrikopoulos S., Subramaniam V.N., Crawford D. Ferroportin expression in adipocytes does not contribute to iron homeostasis or metabolic responses to a high calorie diet. Cell Mol Gastroenterol Hepatol. 2018;5:319–331.
    1. Ellervik C., Birgens H., Tybjaerg-Hansen A., Nordestgaard B.G. Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66,000 cases and 226,000 controls. Hepatology. 2007;46:1071–1080.
    1. Valenti L., Rametta R., Dongiovanni P., Motta B.M., Canavesi E., Pelusi S., Pulixi E.A., Fracanzani A.L., Fargion S. The A736V TMPRSS6 polymorphism influences hepatic iron overload in nonalcoholic fatty liver disease. PLoS One. 2012;7:e48804.
    1. Nelson J.E., Wilson L., Brunt E.M., Yeh M.M., Kleiner D.E., Unalp-Arida A., Kowdley K.V. Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease. Hepatology. 2011;53:448–457.
    1. Valenti L., Fracanzani A.L., Bugianesi E., Dongiovanni P., Galmozzi E., Vanni E., Canavesi E., Lattuada E., Roviaro G., Marchesini G., Fargion S. HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology. 2010;138:905–912.
    1. Brunt E.M., Janney C.G., Di Bisceglie A.M., Neuschwander-Tetri B.A., Bacon B.R. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–2474.
    1. Handa P., Morgan-Stevenson V., Maliken B.D., Nelson J.E., Washington S., Westerman M., Yeh M.M., Kowdley K.V. Iron overload results in hepatic oxidative stress, immune cell activation, and hepatocellular ballooning injury, leading to nonalcoholic steatohepatitis in genetically obese mice. Am J Physiol Gastrointest Liver Physiol. 2016;310:G117–G127.
    1. Maliken B.D., Nelson J.E., Klintworth H.M., Beauchamp M., Yeh M.M., Kowdley K.V. Hepatic reticuloendothelial system cell iron deposition is associated with increased apoptosis in nonalcoholic fatty liver disease. Hepatology. 2013;57:1806–1813.
    1. Valenti L., Fracanzani A.L., Dongiovanni P., Bugianesi E., Marchesini G., Manzini P., Vanni E., Fargion S. Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia: evidence from a case-control study. Am J Gastroenterol. 2007;102:1251–1258.
    1. Valenti L., Fracanzani A.L., Dongiovanni P., Rovida S., Rametta R., Fatta E., Pulixi E.A., Maggioni M., Fargion S. A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia. World J Gastroenterol. 2014;20:3002–3010.
    1. Khodadoostan M., Zamanidoost M., Shavakhi A., Sanei H., Shahbazi M., Ahmadian M. Effects of phlebotomy on liver enzymes and histology of patients with nonalcoholic fatty liver disease. Adv Biomed Res. 2017;6:12.
    1. Adams L.A., Crawford D.H., Stuart K., House M.J., St Pierre T.G., Webb M., Ching H.L., Kava J., Bynevelt M., MacQuillan G.C., Garas G., Ayonrinde O.T., Mori T.A., Croft K.D., Niu X., Jeffrey G.P., Olynyk J.K. The impact of phlebotomy in nonalcoholic fatty liver disease: a prospective, randomized, controlled trial. Hepatology. 2015;61:1555–1564.
    1. Keller H., Dreyer C., Medin J., Mahfoudi A., Ozato K., Wahli W. Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers. Proc Natl Acad Sci U S A. 1993;90:2160–2164.
    1. Issemann I., Prince R.A., Tugwood J.D., Green S. The peroxisome proliferator-activated receptor: retinoid X receptor heterodimer is activated by fatty acids and fibrate hypolipidaemic drugs. J Mol Endocrinol. 1993;11:37–47.
    1. Shiota G. Loss of function of retinoic acid in liver leads to steatohepatitis and liver tumor: a NASH animal model. Hepatol Res. 2005;33:155–160.
    1. Lavigne P.M., Karas R.H. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. J Am Coll Cardiol. 2013;61:440–446.
    1. Green R., Allen L.H., Bjorke-Monsen A.L., Brito A., Gueant J.L., Miller J.W., Molloy A.M., Nexo E., Stabler S., Toh B.H., Ueland P.M., Yajnik C. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3:17040.
    1. Ganji S.H., Qin S., Zhang L., Kamanna V.S., Kashyap M.L. Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells. Atherosclerosis. 2009;202:68–75.
    1. Ganji S.H., Kukes G.D., Lambrecht N., Kashyap M.L., Kamanna V.S. Therapeutic role of niacin in the prevention and regression of hepatic steatosis in rat model of nonalcoholic fatty liver disease. Am J Physiol Gastrointest Liver Physiol. 2014;306:G320–G327.
    1. Ganji S.H., Kashyap M.L., Kamanna V.S. Niacin inhibits fat accumulation, oxidative stress, and inflammatory cytokine IL-8 in cultured hepatocytes: impact on non-alcoholic fatty liver disease. Metabolism. 2015;64:982–990.
    1. Hu M., Chu W.C., Yamashita S., Yeung D.K., Shi L., Wang D., Masuda D., Yang Y., Tomlinson B. Liver fat reduction with niacin is influenced by DGAT-2 polymorphisms in hypertriglyceridemic patients. J Lipid Res. 2012;53:802–809.
    1. Polyzos S.A., Kountouras J., Patsiaoura K., Katsiki E., Zafeiriadou E., Zavos C., Deretzi G., Tsiaousi E., Slavakis A. Serum vitamin B12 and folate levels in patients with non-alcoholic fatty liver disease. Int J Food Sci Nutr. 2012;63:659–666.
    1. Koplay M., Gulcan E., Ozkan F. Association between serum vitamin B12 levels and the degree of steatosis in patients with nonalcoholic fatty liver disease. J Investig Med. 2011;59:1137–1140.
    1. Vos M.B., Colvin R., Belt P., Molleston J.P., Murray K.F., Rosenthal P., Schwimmer J.B., Tonascia J., Unalp A., Lavine J.E. Correlation of vitamin E, uric acid, and diet composition with histologic features of pediatric NAFLD. J Pediatr Gastroenterol Nutr. 2012;54:90–96.
    1. Madan K., Bhardwaj P., Thareja S., Gupta S.D., Saraya A. Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD) J Clin Gastroenterol. 2006;40:930–935.
    1. Harrison S.A., Torgerson S., Hayashi P., Ward J., Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2003;98:2485–2490.
    1. Skaaby T., Husemoen L.L., Borglykke A., Jorgensen T., Thuesen B.H., Pisinger C., Schmidt L.E., Linneberg A. Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine. 2014;47:213–220.
    1. Seo J.A., Eun C.R., Cho H., Lee S.K., Yoo H.J., Kim S.G., Choi K.M., Baik S.H., Choi D.S., Yim H.J., Shin C., Kim N.H. Low vitamin D status is associated with nonalcoholic fatty liver disease independent of visceral obesity in Korean adults. PLoS One. 2013;8:e75197.
    1. Jablonski K.L., Jovanovich A., Holmen J., Targher G., McFann K., Kendrick J., Chonchol M. Low 25-hydroxyvitamin D level is independently associated with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. 2013;23:792–798.
    1. Patel Y.A., Henao R., Moylan C.A., Guy C.D., Piercy D.L., Diehl A.M., Abdelmalek M.F. Vitamin D is not associated with severity in NAFLD: results of a paired clinical and gene expression profile analysis. Am J Gastroenterol. 2016;111:1591–1598.
    1. Bril F., Maximos M., Portillo-Sanchez P., Biernacki D., Lomonaco R., Subbarayan S., Correa M., Lo M., Suman A., Cusi K. Relationship of vitamin D with insulin resistance and disease severity in non-alcoholic steatohepatitis. J Hepatol. 2015;62:405–411.
    1. Barchetta I., Angelico F., Del Ben M., Baroni M.G., Pozzilli P., Morini S., Cavallo M.G. Strong association between non alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes. BMC Med. 2011;9:85.
    1. Liangpunsakul S., Chalasani N. Serum vitamin D concentrations and unexplained elevation in ALT among US adults. Dig Dis Sci. 2011;56:2124–2129.
    1. Roth C.L., Elfers C.T., Figlewicz D.P., Melhorn S.J., Morton G.J., Hoofnagle A., Yeh M.M., Nelson J.E., Kowdley K.V. Vitamin D deficiency in obese rats exacerbates nonalcoholic fatty liver disease and increases hepatic resistin and Toll-like receptor activation. Hepatology. 2012;55:1103–1111.
    1. Beilfuss A., Sowa J.P., Sydor S., Beste M., Bechmann L.P., Schlattjan M., Syn W.K., Wedemeyer I., Mathe Z., Jochum C., Gerken G., Gieseler R.K., Canbay A. Vitamin D counteracts fibrogenic TGF-beta signalling in human hepatic stellate cells both receptor-dependently and independently. Gut. 2015;64:791–799.
    1. Erhardt A., Stahl W., Sies H., Lirussi F., Donner A., Haussinger D. Plasma levels of vitamin E and carotenoids are decreased in patients with nonalcoholic steatohepatitis (NASH) Eur J Med Res. 2011;16:76–78.
    1. Leo M.A., Rosman A.S., Lieber C.S. Differential depletion of carotenoids and tocopherol in liver disease. Hepatology. 1993;17:977–986.
    1. Podszun M.C., Grebenstein N., Spruss A., Schlueter T., Kremoser C., Bergheim I., Frank J. Dietary alpha-tocopherol and atorvastatin reduce high-fat-induced lipid accumulation and down-regulate CD36 protein in the liver of guinea pigs. J Nutr Biochem. 2014;25:573–579.
    1. Nan Y.M., Wu W.J., Fu N., Liang B.L., Wang R.Q., Li L.X., Zhao S.X., Zhao J.M., Yu J. Antioxidants vitamin E and 1-aminobenzotriazole prevent experimental non-alcoholic steatohepatitis in mice. Scand J Gastroenterol. 2009;44:1121–1131.
    1. Raso G.M., Esposito E., Iacono A., Pacilio M., Cuzzocrea S., Canani R.B., Calignano A., Meli R. Comparative therapeutic effects of metformin and vitamin E in a model of non-alcoholic steatohepatitis in the young rat. Eur J Pharmacol. 2009;604:125–131.
    1. Chung M.Y., Yeung S.F., Park H.J., Volek J.S., Bruno R.S. Dietary alpha- and gamma-tocopherol supplementation attenuates lipopolysaccharide-induced oxidative stress and inflammatory-related responses in an obese mouse model of nonalcoholic steatohepatitis. J Nutr Biochem. 2010;21:1200–1206.
    1. Parola M., Leonarduzzi G., Biasi F., Albano E., Biocca M.E., Poli G., Dianzani M.U. Vitamin E dietary supplementation protects against carbon tetrachloride-induced chronic liver damage and cirrhosis. Hepatology. 1992;16:1014–1021.
    1. Nieto N., Friedman S.L., Greenwel P., Cederbaum A.I. CYP2E1-mediated oxidative stress induces collagen type I expression in rat hepatic stellate cells. Hepatology. 1999;30:987–996.
    1. Parola M., Muraca R., Dianzani I., Barrera G., Leonarduzzi G., Bendinelli P., Piccoletti R., Poli G. Vitamin E dietary supplementation inhibits transforming growth factor beta 1 gene expression in the rat liver. FEBS Lett. 1992;308:267–270.
    1. Chalasani N.P., Sanyal A.J., Kowdley K.V., Robuck P.R., Hoofnagle J., Kleiner D.E., Unalp A., Tonascia J. Pioglitazone versus vitamin E versus placebo for the treatment of non-diabetic patients with non-alcoholic steatohepatitis: PIVENS trial design. Contemp Clin Trials. 2009;30:88–96.
    1. Cao Y., Wang C., Liu J., Liu Z.M., Ling W.H., Chen Y.M. Greater serum carotenoid levels associated with lower prevalence of nonalcoholic fatty liver disease in Chinese adults. Sci Rep. 2015;5:12951.
    1. Ruhl C.E., Everhart J.E. Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States. Gastroenterology. 2003;124:1821–1829.
    1. Sugiura M., Nakamura M., Ogawa K., Ikoma Y., Yano M. High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study. Br J Nutr. 2016;115:1462–1469.
    1. Xiao M.L., Chen G.D., Zeng F.F., Qiu R., Shi W.Q., Lin J.S., Cao Y., Li H.B., Ling W.H., Chen Y.M. Higher serum carotenoids associated with improvement of non-alcoholic fatty liver disease in adults: a prospective study. Eur J Nutr. March 29, 2018 Epub ahead of print.
    1. Seif El-Din S.H., El-Lakkany N.M., El-Naggar A.A., Hammam O.A., Abd El-Latif H.A., Ain-Shoka A.A., Ebeid F.A. Effects of rosuvastatin and/or beta-carotene on non-alcoholic fatty liver in rats. Res Pharm Sci. 2015;10:275–287.
    1. Kobori M., Ni Y., Takahashi Y., Watanabe N., Sugiura M., Ogawa K., Nagashimada M., Kaneko S., Naito S., Ota T. beta-Cryptoxanthin alleviates diet-induced nonalcoholic steatohepatitis by suppressing inflammatory gene expression in mice. PLoS One. 2014;9:e98294.
    1. Ni Y., Nagashimada M., Zhan L., Nagata N., Kobori M., Sugiura M., Ogawa K., Kaneko S., Ota T. Prevention and reversal of lipotoxicity-induced hepatic insulin resistance and steatohepatitis in mice by an antioxidant carotenoid, beta-cryptoxanthin. Endocrinology. 2015;156:987–999.
    1. Ni Y., Nagashimada M., Zhuge F., Zhan L., Nagata N., Tsutsui A., Nakanuma Y., Kaneko S., Ota T. Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: a comparison with vitamin E. Sci Rep. 2015;5:17192.
    1. Ikeuchi M., Koyama T., Takahashi J., Yazawa K. Effects of astaxanthin in obese mice fed a high-fat diet. Biosci Biotechnol Biochem. 2007;71:893–899.
    1. Miranda-Vilela A.L., Akimoto A.K., Alves P.C., Pereira L.C., Goncalves C.A., Klautau-Guimaraes M.N., Grisolia C.K. Dietary carotenoid-rich pequi oil reduces plasma lipid peroxidation and DNA damage in runners and evidence for an association with MnSOD genetic variant -Val9Ala. Genet Mol Res. 2009;8:1481–1495.
    1. Dasarathy J., Varghese R., Feldman A., Khiyami A., McCullough A.J., Dasarathy S. Patients with nonalcoholic fatty liver disease have a low response rate to vitamin D supplementation. J Nutr. 2017;147:1938–1946.
    1. Sanyal A.J., Chalasani N., Kowdley K.V., McCullough A., Diehl A.M., Bass N.M., Neuschwander-Tetri B.A., Lavine J.E., Tonascia J., Unalp A., Van Natta M., Clark J., Brunt E.M., Kleiner D.E., Hoofnagle J.H., Robuck P.R. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–1685.
    1. Lavine J.E., Schwimmer J.B., Van Natta M.L., Molleston J.P., Murray K.F., Rosenthal P., Abrams S.H., Scheimann A.O., Sanyal A.J., Chalasani N., Tonascia J., Unalp A., Clark J.M., Brunt E.M., Kleiner D.E., Hoofnagle J.H., Robuck P.R. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011;305:1659–1668.
    1. Chalasani N., Younossi Z., Lavine J.E., Charlton M., Cusi K., Rinella M., Harrison S.A., Brunt E.M., Sanyal A.J. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328–357.
    1. Blond E., Disse E., Cuerq C., Drai J., Valette P.J., Laville M., Thivolet C., Simon C., Caussy C. EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease in severely obese people: do they lead to over-referral? Diabetologia. 2017;60:1218–1222.
    1. Venu M., Martin E., Saeian K., Gawrieh S. High prevalence of vitamin A deficiency and vitamin D deficiency in patients evaluated for liver transplantation. Liver Transplant. 2013;19:627–633.
    1. Cipriani S., Mencarelli A., Palladino G., Fiorucci S. FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats. J Lipid Res. 2010;51:771–784.
    1. Neuschwander-Tetri B.A., Loomba R., Sanyal A.J., Lavine J.E., Van Natta M.L., Abdelmalek M.F., Chalasani N., Dasarathy S., Diehl A.M., Hameed B., Kowdley K.V., McCullough A., Terrault N., Clark J.M., Tonascia J., Brunt E.M., Kleiner D.E., Doo E. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015;385:956–965.
    1. Pickett-Blakely O., Newberry C. Future therapies in obesity. Gastroenterol Clin North Am. 2016;45:705–714.
    1. Romero-Gomez M., Zelber-Sagi S., Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017;67:829–846.
    1. Zelber-Sagi S., Salomone F., Mlynarsky L. The Mediterranean dietary pattern as the diet of choice for non-alcoholic fatty liver disease: evidence and plausible mechanisms. Liver Int. 2017;37:936–949.
    1. Eslamparast T., Tandon P., Raman M. Dietary composition independent of weight loss in the management of non-alcoholic fatty liver disease. Nutrients. 2017;9

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