SAMe
Research reviewed: Up until 03/2026
SAMe (S-Adenosyl Methionine) is a dietary supplement with 10 published peer-reviewed studies involving 607 participants, researched for Depression & Mood, Liver Health, Osteoarthritis and 2 more areas.
Evidence at a Glance
Strength is scored by study design, sample size, study type, and outcomes
Depression & Mood
ModerateLiver Health
StrongOsteoarthritis
WeakFibromyalgia
ModerateMental Health & Cardiovascular
ModerateResearch Visualised
Visual breakdown of the clinical data.
Study Quality Breakdown
What types of studies were conducted
Participants Per Study
Larger samples = more reliable results
Research Timeline
When the studies were published
All Studies
Detailed breakdown of each trial. Click to expand.
Depression & Mood
To compare SAMe to imipramine for major depressive disorder.
Study Type
Randomised, double-blind, controlled
Purpose
To compare SAMe to imipramine for major depressive disorder.
Dose
1,600 mg/day oral SAMe vs 150 mg/day imipramine
Participants
281 patients with major depression
Duration
6 weeks
Results
SAMe produced comparable antidepressant effects to imipramine with significantly fewer adverse effects. HAM-D score reductions were similar between groups, establishing SAMe as an effective antidepressant.
How They Measured It
Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression
To evaluate the efficacy of SAMe for depression compared to placebo and antidepressants.
Study Type
Systematic review and meta-analysis
Purpose
To evaluate the efficacy of SAMe for depression compared to placebo and antidepressants.
Dose
400-1,600 mg/day
Participants
Pooled from 8 RCTs
Duration
3-8 weeks
Results
SAMe was significantly more effective than placebo and comparable to tricyclic antidepressants. As adjunctive therapy to SSRIs, SAMe showed superior response and remission rates versus placebo.
How They Measured It
Pooled HAM-D scores, response and remission rates
To evaluate SAMe as adjunctive therapy for SSRI-resistant depression.
Study Type
Randomised, double-blind, placebo-controlled
Purpose
To evaluate SAMe as adjunctive therapy for SSRI-resistant depression.
Dose
800 mg twice daily SAMe
Participants
73 adults with antidepressant-resistant MDD
Duration
6 weeks
Results
SAMe augmentation significantly improved response rate (36.1% vs 17.6%) and remission rate (25.8% vs 11.7%) compared to placebo. SAMe is a valuable augmentation strategy for treatment-resistant depression.
How They Measured It
HAM-D, MADRS, response and remission rates
Liver Health
To assess SAMe supplementation on liver function in alcoholic liver disease.
Study Type
Randomised, double-blind, placebo-controlled
Purpose
To assess SAMe supplementation on liver function in alcoholic liver disease.
Dose
1,200 mg/day SAMe
Participants
123 patients with alcoholic liver cirrhosis
Duration
2 years
Results
SAMe supplementation significantly reduced liver-related mortality and transplantation rates in patients with less severe disease (Child-Pugh A and B). Liver enzyme improvements were also significant.
How They Measured It
ALT, AST, GGT, bilirubin, mortality at 2-year follow-up
To evaluate SAMe supplementation on intrahepatic cholestasis of pregnancy.
Study Type
Randomised, double-blind, placebo-controlled
Purpose
To evaluate SAMe supplementation on intrahepatic cholestasis of pregnancy.
Dose
1,000 mg/day iv SAMe transitioning to oral
Participants
78 pregnant women with intrahepatic cholestasis
Duration
Until delivery
Results
SAMe significantly reduced serum bile acids and improved pruritus in pregnant women with intrahepatic cholestasis. Perinatal outcomes were improved compared to placebo.
How They Measured It
Serum bile acids, ALT, pruritus score, perinatal outcomes
Osteoarthritis
To evaluate SAMe for pain and function in osteoarthritis.
Study Type
Meta-analysis
Purpose
To evaluate SAMe for pain and function in osteoarthritis.
Dose
600-1,200 mg/day
Participants
Pooled from multiple RCTs
Duration
Various
Results
SAMe significantly reduced pain and improved joint function in osteoarthritis patients. Effect size was comparable to NSAIDs with fewer gastrointestinal side effects, making it a viable alternative.
How They Measured It
Pain VAS, WOMAC, functional assessment across RCTs
Fibromyalgia
To evaluate SAMe supplementation for fibromyalgia symptoms.
Study Type
Randomised, double-blind, placebo-controlled
Purpose
To evaluate SAMe supplementation for fibromyalgia symptoms.
Dose
800 mg/day oral SAMe
Participants
44 patients with fibromyalgia
Duration
6 weeks
Results
SAMe significantly improved tender point count, pain, fatigue, and mood scores in fibromyalgia patients compared to placebo. The multimodal effects of SAMe (analgesia and mood) make it well suited for this condition.
How They Measured It
Tender point count, pain VAS, fatigue score, mood assessment
To examine SAMe's mechanism of action on central sensitisation and pain pathways.
Study Type
Animal study
Purpose
To examine SAMe's mechanism of action on central sensitisation and pain pathways.
Dose
Pharmacological SAMe doses
Participants
Sprague-Dawley rats
Duration
21 days
Results
SAMe increased central serotonin and dopamine synthesis, supporting its dual role as analgesic and antidepressant. Substance P modulation may also contribute to its fibromyalgia benefits.
How They Measured It
Substance P, serotonin and dopamine brain levels, pain behavioural tests
Mental Health & Cardiovascular
To evaluate the efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients.
Study Type
Systematic Review and Meta-Analysis
Purpose
To evaluate the efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients.
Dose
Various doses across included trials (typically 800-1600 mg/day)
Participants
Meta-analysis of patients with depression
Duration
Various
Results
SAMe supplementation demonstrated significant antidepressant efficacy with favorable tolerability profile comparable to conventional antidepressants.
How They Measured It
Depression rating scales (HAM-D, MADRS), remission rates, adverse events
To evaluate lowering plasma S-adenosylhomocysteine (SAH) in healthy adults using SAMe supplementation.
Study Type
Randomized Controlled Trial
Purpose
To evaluate lowering plasma S-adenosylhomocysteine (SAH) in healthy adults using SAMe supplementation.
Dose
SAMe nutritional supplement
Participants
Healthy adults with elevated SAH
Duration
12 weeks
Results
SAMe-based nutritional supplementation significantly lowered plasma SAH levels in healthy adults, potentially reducing cardiovascular risk.
How They Measured It
Plasma SAH levels, homocysteine, methionine cycle markers
Frequently Asked Questions
Common questions about SAMe research
There are currently 10 peer-reviewed studies on SAMe (S-Adenosyl Methionine), involving 607 total participants. Research covers Depression & mood, Liver health, Osteoarthritis and 1 more areas. The overall evidence strength is rated as Strong.
The evidence is currently rated as "Strong Evidence". This rating is based on study design quality (randomisation, blinding, placebo controls), sample sizes, study types (6 human studies, 1 animal study), and reported outcomes.
SAMe has been researched for: Depression & mood, Liver health, Osteoarthritis, Fibromyalgia. Each area has its own body of evidence which you can explore in the study breakdowns above.
Yes, 6 out of 10 studies are human trials. The remaining 1 is an animal study. Human trials carry more weight in our evidence scoring system.
Similar Supplements
Other supplements researched for similar health goals
