SAMe,
does it really help with Reduced risk of death or liver transplantation in alcoholic cirrhosis?
research showsSAMe is rated at the bottom of C for death or liver transplantation in alcoholic cirrhosis. The pivotal 123-person, two-year trial found a large direct hard-outcome signal, with death or transplantation of 30% on placebo versus 16% on SAMe, but the primary endpoint was nonsignificant at p=0.077 and the study was underpowered. The 29% versus 12%, p=0.025 result after excluding eight Child class C participants was a subgroup analysis, not confirmation. The Cochrane death-or-transplant estimate of RR 0.55 with a 95% CI of 0.27 to 1.09 was imprecise, spanning a large benefit through no effect, and no independent confirmatory trial exists. Under the rule ① ceiling for a null primary endpoint, the large estimate and hard-outcome directness support C with 41 points.
ads claimMarketing turns methyl donation and glutathione synthesis into claims of liver regeneration, longer survival in cirrhosis, and delayed transplantation. The pivotal clinical trial produced an encouraging numerical difference but a statistically nonsignificant overall endpoint, and a mechanism or enzyme change is not the same as fewer deaths or transplants.
Useful facts when choosing a product
- The pivotal alcoholic-cirrhosis trial used oral SAMe 1,200 mg per day for two years but did not obtain a statistically significant overall death-or-transplant result.
- SAMe can be unstable with heat and moisture, and salt form, enteric coating, storage, and actual content vary among supplements, so the trial formulation cannot represent every product.
- Alcohol abstinence, nutrition, prevention and treatment of cirrhosis complications, liver-cancer surveillance, and transplant evaluation remain the core of survival-oriented care and must not be replaced by SAMe.
- Usually mild nausea, abdominal discomfort, insomnia, or anxiety can occur, while people with bipolar disorder face a rare risk of mania or hypomania and should review combinations with serotonergic medicines with a clinician.
What the research actually shows
Mato and colleagues enrolled 123 patients with alcoholic cirrhosis, with histological confirmation in 84%, including 75 in Child class A, 40 in B, and eight in C, and treated them in a multicenter double-blind trial for two years. Death or transplantation in the full analysis was 30% versus 16%, a large difference, but the primary endpoint was nonsignificant at p=0.077 and the trial was underpowered. Excluding Child class C produced 29% versus 12%, p=0.025, with survival-curve p=0.046, but this was a subgroup analysis. The Cochrane death-or-transplant estimate was RR 0.55 with a 95% CI of 0.27 to 1.09, spanning large benefit through no effect. The later 37-person trial was null and not sized for death or transplantation, and no large independent confirmatory trial exists.
Why this is classified as C (41)
The direct pivotal trial showed a large hard-outcome estimate of 30% versus 16% death or transplantation, but the primary result was nonsignificant at p=0.077 and underpowered. The Cochrane RR of 0.55 had an imprecise 95% CI of 0.27 to 1.09, the Child class C-excluded result was an unconfirmed subgroup analysis, and no independent confirmation exists. The null-primary-endpoint ceiling applies, but the limited direct hard-outcome signal supports bottom-of-C with 41 points rather than D. Product variation and adverse effects remain separate.
Counterpoint. A real effect in less advanced Child class A or B disease remains possible. It would require a sufficiently large, prospectively stratified trial on top of modern standard care that tests death, transplantation, and cirrhosis complications; current evidence does not support taking SAMe for a survival benefit.
Rejudgment record. Cross-check incorporated — Applied the rule ① ceiling of C because the 123-person, two-year trial produced a large direct death-or-transplant estimate of 30% versus 16% but the primary endpoint was nonsignificant at p=0.077 and underpowered; the Child class C-excluded result was a subgroup analysis, the Cochrane RR of 0.55 had an imprecise 95% CI of 0.27 to 1.09, and no independent confirmatory trial exists. The limited hard-outcome signal supports the bottom of C rather than D
Sub-claim grades by effect
This ingredient is marketed for several effects. A single overall grade blends strong and weak claims together, so each effect is graded separately here. The overall grade reflects the strongest disconfirming or core claim.
| Effect (sub-claim) | Grade | Basis |
|---|---|---|
| Reduced death or liver transplantation in the full alcoholic-cirrhosis population | C | The pivotal 123-person, two-year trial showed a large hard-outcome signal of 30% versus 16%, but the primary endpoint was nonsignificant at p=0.077, underpowered, and unconfirmed independently. |
| Reduced all-cause mortality in alcoholic cirrhosis | C | The Cochrane all-cause mortality estimate was RR 0.62 with an imprecise 95% CI of 0.30 to 1.26, spanning large benefit through no effect, without a confirmatory trial. |
| Reduced death or transplantation in Child class A or B alcoholic cirrhosis | C | Excluding eight Child class C participants produced 29% versus 12%, p=0.025, but this was a subgroup analysis without independent confirmation. |
Cross-check — Codex and Claude
Evidence Table
| Study | Design | Sample | Funding | Endpoint | Result | Weight |
|---|---|---|---|---|---|---|
| Mato JM et al. 1999 | Multicenter randomized double-blind placebo-controlled trial | 2 | Funding source not reported in the PubMed abstract | All-cause death or liver transplantation | The result was 30% with placebo versus 16% with SAMe but nonsignificant at p=0.077; only exclusion of Child class C produced 29% versus 12%, p=0.025. | Pivotal direct hard outcome with a large estimate but a nonsignificant, underpowered primary analysis |
| Rambaldi A, Gluud C. 2006 | Cochrane systematic review and meta-analysis of randomized trials | 434 | Academic Cochrane Hepato-Biliary Group review | All-cause mortality, liver-related mortality, death or transplantation, and complications | Both all-cause mortality RR 0.62 and death-or-transplant RR 0.55 had confidence intervals crossing no effect. | Imprecise pooled estimate without confirmation |
| Medici V et al. 2011 | Randomized double-blind placebo-controlled trial | 24 | Funding source not reported in the PubMed abstract | Liver enzymes, clinical and biochemical measures, and liver histology | The cohort improved with abstinence, but no clinical, biochemical, or histological difference appeared between SAMe and placebo. | Later small null trial |
Receipt — 3 References
All 3 cited sources were verified for existence at the original page (as of 2026-07-21).
Reviewed and approved: Chamgap Editorial Team · Approval date: 2026-07-21 · Corrections: none
Cite this verdict
[Chamgap] SAMe x reduced death or liver transplantation in alcoholic cirrhosis — Evidence Grade C·41. 3 cited sources checked. Source: https://chamgap.com/en/verdicts/liver/same-alcoholic-cirrhosis-death-liver-transplantation/ · CC BY 4.0CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.
What this document does and does not do
Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.