S-adenosyl-L-methionine Treatment for Alcoholic Liver Disease: A Double-Blinded, Randomized, Placebo-Controlled Trial

Authors

  • Valentina Medici,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • Maria C. Virata,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • Janet M. Peerson,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • Sally P. Stabler,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • Samuel W. French,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • Jesse F. Gregory III,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • Anthony Albanese,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • Christopher L. Bowlus,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • Sridevi Devaraj,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • Edward A. Panacek,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • John R. Richards,

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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  • Charles H. Halsted

    1. From the Department of Internal Medicine (VM, MCV, CLB, CHH), University of California Davis, Sacramento, California; Department of Nutrition (JMP), University of California Davis, Sacramento, California; University of Colorado School of Medicine (SPS), Aurora, Colorado; Department of Pathology (SWF), UCLA/Harbor Medical Center, Torrance, California; Food Science and Human Nutrition Department (JFG), Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida; Gastroenterology Section (AA), Sacramento Veterans Affairs Medical Center, Mather, California; Department of Pathology (SD), University of California Davis, Sacramento, California; Department of Emergency Medicine (EAP, JRR), University of California Davis, Sacramento, California.
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Reprint requests: Valentina Medici, Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of California Davis, 4150 V Street, Suite 3500, Sacramento, CA 95817; Tel.: 916-734-3751; Fax: 916-734-7908; E-mail valentina.medici@ucdmc.ucdavis.edu

Abstract

Background:  S-adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione, the main cellular antioxidant. Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases (ALDs). The aim of this study was to determine the efficacy of SAM in treatment for ALD in a 24-week trial. The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores, and the secondary endpoints were changes in serum levels of methionine metabolites.

Methods:  We randomized 37 patients with ALD to receive 1.2 g of SAM by mouth or placebo daily. Subjects were required to remain abstinent from alcohol drinking. A baseline liver biopsy was performed in 24 subjects, and a posttreatment liver biopsy was performed in 14 subjects.

Results:  Fasting serum SAM levels were increased over timed intervals in the SAM treatment group. The entire cohort showed an overall improvement of AST, ALT, and bilirubin levels after 24 weeks of treatment, but there were no differences between the treatment groups in any clinical or biochemical parameters nor any intra- or intergroup differences or changes in liver histopathology scores for steatosis, inflammation, fibrosis, and Mallory-Denk hyaline bodies.

Conclusions:  Whereas abstinence improved liver function, 24 weeks of therapy with SAM was no more effective than placebo in the treatment for ALD.

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