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These impairments ultimately lead to the generation of several hallmark features of alcoholic liver injury including steatosis. Guanidinoacetate methyltransferase (<jats:styled-content style=\"fixed-case\">GAMT<\/jats:styled-content>) is an important enzyme that catalyzes the final reaction in the creatine biosynthetic process. The liver is a major site for creatine synthesis which places a substantial methylation burden on this organ as <jats:styled-content style=\"fixed-case\">GAMT<\/jats:styled-content>\u2010mediated reactions consume as much as 40% of all the <jats:styled-content style=\"fixed-case\">SAM<\/jats:styled-content>\u2010derived methyl groups. We hypothesized that dietary creatine supplementation could potentially spare <jats:styled-content style=\"fixed-case\">SAM<\/jats:styled-content>, preserve the hepatocellular <jats:styled-content style=\"fixed-case\">SAM<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">SAH<\/jats:styled-content> ratio, and thereby prevent the development of alcoholic steatosis and other consequences of impaired methylation reactions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For these studies, male Wistar rats were pair\u2010fed the Lieber\u2010DeCarli control or ethanol (EtOH) diet with or without 1% creatine supplementation. At the end of 4 to 5\u00a0weeks of feeding, relevant biochemical and histological analyses were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed that creatine supplementation neither prevented alcoholic steatosis nor attenuated the alcohol\u2010induced impairments in proteasome activity. The lower hepatocellular <jats:styled-content style=\"fixed-case\">SAM<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">SAH<\/jats:styled-content> ratio seen in the EtOH\u2010fed rats was also not normalized or <jats:styled-content style=\"fixed-case\">SAM<\/jats:styled-content> levels spared when these rats were fed the creatine\u2010supplemented EtOH diet. However, a &gt;10\u2010fold increased level of creatine was observed in the liver, serum, and hearts of rats fed the creatine\u2010supplemented diets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, dietary creatine supplementation did not prevent alcoholic liver injury despite its known efficacy in preventing high\u2010fat\u2010diet\u2010induced steatosis. Betaine, a promethylating agent that maintains the hepatocellular <jats:styled-content style=\"fixed-case\">SAM<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\">SAH<\/jats:styled-content>, still remains our best option for treating alcoholic steatosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13214","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T18:24:17Z","timestamp":1472754257000},"page":"2312-2319","source":"Crossref","is-referenced-by-count":12,"title":["Creatine Supplementation Does Not Prevent the Development of Alcoholic Steatosis"],"prefix":"10.1111","volume":"40","author":[{"given":"Murali","family":"Ganesan","sequence":"first","affiliation":[{"name":"Research Service Veterans Affairs Nebraska\u2010Western Iowa Health Care System Omaha Nebraska"},{"name":"Department of Internal Medicine University of Nebraska Medical Center Omaha 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