Prior studies in animal models have established that the pathogenesis of alcoholic liver disease (ALD) is regulated in part by the effects of chronic alcohol abuse on hepatic methionine metabolism. The hypothesis of the clinical study was that provision of the methionine metabolite S-adenosylmethionine (SAM) would correct abnormal hepatic methionine metabolism thereby effectively treating ALD. The two goals of the clinical research were a)to determine the clinical relationship of aberrant hepatic methionine metabolism to ALD by comparisons of patterns of serum methionine metabolites in groups of ALD patients, alcoholics without liver disease, and normal healthy subjects, and b) to determine the treatment effects of SAM on patterns of serum methionine metabolites and on the histopathology and biochemical features of liver injury in ALD patients.

We assessed a total of 297 potential ALD candidates, from whom 40 were enrolled in the study. In addition, we enrolled 26 gender matched active alcohol drinkers without liver disease (AD) and 28 age and gender matched healthy control subjects (HS). Of the original 40 ALD subjects who provided initial enrollment data, 3 declined to proceed with the trial. Therefore, 37 ALD patients were randomized to receive SAM at a dose of 400 mg or placebo three times daily for 24 weeks. However 11 of these dropped out after initial evaluation, leaving 26 ALD patients, 13 in each arm, who completed the 24 week trial.

Inclusion Criteria

• ALD) a history of chronic alcoholism according to established AUDIT and WHO criteria with the presence of clinical and laboratory features of established liver disease. Also, willingness to undergo liver biopsies at start and completion of the study, and to comply with study medication or placebo and required clinic visits and blood sampling.
• a history of chronic alcoholism without evidence of liver disease;
• healthy subjects without history of alcoholism or presence of liver disease.

Exclusion Criteria:

• viral Hepatitis B or C
• hemochromatosis
• Wilson Disease
• sclerosing cholangitis
• primary biliary cirrhosis
• other chronic disease
• renal insufficiency

294 patients were screened of whom 37 were selected for the SAMe v sugar pill trial. Of those excluded, 128 did not meet inclusion criteria, 105 met inclusion criteria but were excluded because of lack of reliable contact information, and 24 subjects declined to participate, leaving 37 subjects, 18 and 19 in each respective group at baseline.

Adverse events were only measured in participants with alcoholic liver disease who were randomized to receive intervention.

Relatively small numbers of subjects analyzed with 13 each completers in the treatment and placebo groups. Within each group, violation of protocal by resumption of alcohol intake accounted for dropouts.