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Head-to-head evidence comparison — which supplement is right for you?
SAMe wins 1 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Mostly mechanism / observational
0 of 2 studies with measurable effects showed benefit.
Top outcomes
Verdict
Mixed evidence
4 of 9 studies with measurable effects showed benefit.
Top outcomes
Shared outcomes (2)
Outcomes where both SAMe and St. John's Wort have evidence — compare verdict strength side-by-side.
400-1600mg for mood; 600-1200mg for joints
On empty stomach, Morning and/or midday
Enteric-coated tablets (SAMe tosylate or butanedisulfonate)
300mg 3x daily (900mg total)
With meals, Divided into 2-3 doses
Standardized extract (0.3% hypericin)
2-6 weeks
4-8 weeks
4-8 weeks
4-6 weeks
4-8 weeks
During use
First 1-2 weeks
S-Adenosylmethionine for osteoarthritis of the knee or hip
The Cochrane database of systematic reviews (2009) · Meta analysis · n=656
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).
Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis
Neuropsychopharmacology reports (2025) · Meta analysis · n=1049
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).
S-Adenosylmethionine (SAMe) for Liver Health: A Systematic Review
Nutrients (2024) · Systematic review · n=15
The most common doses were SAMe 1000 mg or 1200 mg per day with or without another treatment or natural supplement.
St John's wort for major depression
Cochrane Database of Systematic Reviews (2008) · Meta analysis · n=5489
As effective as standard antidepressants for mild-moderate depression
Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis
Neuropsychopharmacology reports (2025) · Meta analysis · n=1049
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).
Systematic Review and Network Meta-Analysis of the Effects of Plant Extracts on Cognitive Function and Quality of Life in Stroke Patients
Phytotherapy research : PTR (2025) · Meta analysis
John's Wort extract (SUCRA 71.2%) was the most effective in reducing NIHSS scores, Berberine (SUCRA 84.1%) was most effective in reducing mRS scores, and St.
Meta-analysis of 656 patients showed small effect size (SMD -0.17) corresponding to only 0.4cm improvement on 10cm pain scale. Effect is modest and barely reaches statistical significance threshold.
Based on multiple meta-analyses (n>5000) showing efficacy comparable to SSRIs for mild-moderate depression. Effect plateau around 900-1200mg. Not effective for severe depression. Requires standardized extract (0.3% hypericin).
AI-estimated from published studies. Interpret as directional guidance.
SAMe has a higher evidence score (9/10 vs 9/10) and wins in 1 of 3 categories.
For support mood, St. John's Wort has a higher relevance score (92 vs 90).
No known interactions between SAMe and St. John's Wort have been documented in our database. However, always consult a healthcare provider before combining supplements.