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Sam7.0
SAMe Research
Mixed evidence
93 peer-reviewed studies
What the evidence says
Mixed evidence
Studies are split: SAMe helped in 1 of 3 cases, with the rest inconclusive or showing no benefit.
Most evidence is from high-quality meta-analyses and randomised trials published 1984–2026 with a typical study size of 656 participants.
Based on 93 studies · 16 meta-analyses · 62 RCTs · 6,474 total participants
Confidence
High confidence
What the studies found
1helped2unclear· 90 more without graded effect data
By outcome
Depression & moodSignificant improvement in depressive symptoms · 2-6 weeks
Mixed evidence79 studies
Therapeutic & clinical
Mostly mechanism / observational26 studies
Liver health
Mostly mechanism / observational23 studies
Women's health
Mostly mechanism / observational14 studies
Joint pain & arthritisComparable to NSAIDs for osteoarthritis pain in clinical trials · 4-8 weeks
Mostly mechanism / observational13 studies
Cognitive function
Mostly mechanism / observational4 studies
Neuroprotection & brain aging
Mostly mechanism / observational3 studies
Energy & fatigue
Too few graded studies2 studies
Heart & blood pressure
Too few graded studies1 study
Safety profile
Too few graded studies1 study
By the numbers
Pulled from 14 studies with measurable effects
People studied
6,474
typical study: 656 people
Strongest designs
78
16 pooled, 62 randomised
Showed benefit
33%
1/3 studies
How long studies ran
1–3 months
2
Populations Studied
Patients with depression2
Adults with mild depression1
Participants receiving SAM supplementation1
Patients with liver diseases1
Steady research
19 studies in the last 5 years · Latest meta-analysis: 2025
198420052026
1Depression response ratesMeta-Analysisn=1,049 · large study2025
This review demonstrates that certain supplements, such as eicosapentaenoic acids and Rhodiola rosea, are therapeutic options for mild depression.
Urata M et al. · Neuropsychopharmacology reports (2025)
No clear effect
← WorseNo effectBetter →
A meta-analysis found no significant difference in response rates between the two treatments (risk ratio [RR] = 0.96, 95% CI: 0.78-1.18) or dropout rates (RR = 1.08, 95% CI: 0.62-1.88).
Eicosapentaenoic acid and Rhodiola rosea demonstrated significant improvements in depressive symptoms compared to placebo.
Conversely, S-adenosylmethionine did not produce significant improvements relative to placebo.
17Pain reductionMeta-AnalysisCited 40×n=656 · large study2009
The current systematic review is inconclusive, hampered by the inclusion of mainly small trials of questionable quality.
Rutjes AW et al. · The Cochrane database of systematic reviews (2009)
No clear effect
← WorseNo effectBetter →
For pain, the analysis indicated a small SMD of -0.17 (95% CI -0.34 to 0.01), corresponding to a difference in pain scores between SAMe and placebo of 0.4 cm on a 10 cm VAS, with no between trial heterogeneity (I(2) = 0).
For function, the analysis suggested a SMD of 0.02 (95% CI -0.68 to 0.71) with a moderate degree of between-trial heterogeneity (I2 = 54%).
The current systematic review is inconclusive, hampered by the inclusion of mainly small trials of questionable quality.
The results of SAMe versus placebo as a monotherapy, SAMe versus imipramine or escitalopram as a monotherapy, and SAMe versus placebo as an adjunctive therapy, showed no significant difference in depression with SAMe compared to the comparison treatment.
Conclusions SAMe may provide relief of depression symptoms similar to imipramine or escitalopram.
However, the results of the comparisons should be interpreted with caution due to the small number of studies and the large range of SAMe doses that were used in the included trials.