Transmetil (SAMe) Does Not Improve Survival in Alcoholic Cirrhosis
Based on the highest quality evidence, S-adenosyl-L-methionine (SAMe, marketed as Transmetil) should not be prescribed for alcoholic cirrhosis as it has not demonstrated unequivocal efficacy on mortality or liver-related outcomes. 1, 2
Evidence Summary
Guideline Consensus: No Proven Benefit
The most authoritative guidelines uniformly conclude against SAMe use:
The European Association for the Study of the Liver (EASL) explicitly states that no specific pharmacological therapy for alcoholic cirrhosis, including SAMe, has demonstrated unequivocal efficacy (2012 and 2018 guidelines). 1
The American Association for the Study of Liver Diseases reviewed a Cochrane meta-analysis of 9 randomized controlled trials (434 patients) that found no significant benefit of SAMe on total mortality, liver-related mortality, complications, or liver transplantation. 1, 2
The Single Positive Trial vs. Meta-Analysis
While one 1999 trial by Mato et al. showed improved survival in Child-Pugh A and B patients (mortality/transplantation 12% vs 29%, p=0.025), this finding was not replicated in subsequent meta-analyses. 3, 4
The 2006 Cochrane review found no significant effects on:
- All-cause mortality (RR 0.62,95% CI 0.30-1.26)
- Liver-related mortality (RR 0.68,95% CI 0.31-1.48)
- Mortality or transplantation combined (RR 0.55,95% CI 0.27-1.09)
- Complications (RR 1.35,95% CI 0.84-2.16) 4
A 2011 double-blind RCT found no differences between SAMe and placebo in any clinical, biochemical, or histopathological parameters after 24 weeks of treatment. 5
Clinical Approach
What to Prioritize Instead
Alcohol abstinence is the major therapeutic goal with the strongest evidence for mortality reduction—SAMe should not be prescribed as primary therapy. 2, 6
Focus on proven interventions:
- Complete alcohol abstinence (reduces complications and mortality) 1
- Aggressive nutritional therapy with frequent interval feedings, emphasizing nighttime snacks and morning feeding to improve nitrogen balance 1
- Standard cirrhosis management including screening and prophylaxis for varices, hepatocellular carcinoma surveillance, and management of ascites/encephalopathy 1
If SAMe Is Considered Despite Lack of Evidence
If a patient insists or you choose to trial SAMe as adjunctive therapy:
- Dose: 1200 mg orally daily (typically divided into doses) 6, 3
- Duration: 6 months to 2 years based on trial protocols 6
- Clearly counsel the patient that mortality benefit is unproven and SAMe should not substitute for alcohol abstinence or standard cirrhosis management 6, 7
Important Caveats
- Do not use SAMe expecting mortality reduction or prevention of decompensation based on current evidence 6
- SAMe demonstrates favorable tolerability with primarily mild, transient gastrointestinal complaints 2, 7
- Avoid in bipolar disorder (increases cycling) and use caution with other serotonergic medications due to potential serotonin syndrome 7
Why the Discrepancy Between Theory and Practice?
Despite strong theoretical rationale (SAMe serves as a methyl donor and glutathione precursor, addressing oxidative stress in alcoholic liver disease), clinical trials have failed to demonstrate consistent benefits on hard endpoints. 1, 2 Animal models showed promise, but this has not translated to human efficacy. 8