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Head-to-head evidence comparison — which supplement is right for you?
St. John's Wort vs Tryptophan: Tryptophan has the stronger overall evidence (5.5 vs 7.8/10); take care combining them — there's a flagged interaction. Take the 60-second quiz for a pick tailored to your goals.
Tryptophan wins 2 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Mixed evidence
4 of 9 studies with measurable effects showed benefit.
Top outcomes
Verdict
Likely helps
5 of 7 studies with measurable effects showed benefit.
Top outcomes
Shared outcomes (2)
Outcomes where both St. John's Wort and Tryptophan have evidence — compare verdict strength side-by-side.
300mg 3x daily (900mg total)
With meals, Divided into 2-3 doses
Standardized extract (0.3% hypericin)
500-1000mg before bed
30-60 minutes before bed, On empty stomach or with carbohydrates
L-Tryptophan capsules
and 21 more not shown
and 2 more not shown
Risk of serotonin syndrome: agitation, tremor, hyperthermia, tachycardia
Do not combine without medical supervision
4-6 weeks
4-8 weeks
During use
First 1-2 weeks
30-60 minutes
1-2 weeks
1-2 weeks
1-2 hours after dose
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.
The Tryptophan Catabolite or Kynurenine Pathway in a Major Depressive Episode with Melancholia, Psychotic Features and Suicidal Behaviors: A Systematic Review and Meta-Analysis
Cells (2022) · Meta analysis · n=4647
Severe patients showed significant lower (p < 0.0001) TRP (standardized mean difference, SMD = -0.517, 95% confidence interval, CI: -0.735; -0.299) and TRP/CAAs (SMD = -0.617, CI: -0.957; -0.277) levels with moderate effect sizes, while no significant difference in CAAs were found.
Comparative efficacy and tolerability of nutraceuticals for depressive disorder: A systematic review and network meta-analysis
Psychological medicine (2025) · Meta analysis · n=17437
Adjunctive nutraceuticals consistently showed better efficacy than antidepressants (ADT) alone in outcomes including SMD, remission, and response.
Differential Metabolites in Osteoarthritis: A Systematic Review and Meta-Analysis
Nutrients (2023) · Meta analysis · n=495
In the 13 studies, 132 kinds of small molecule differential metabolites were extracted, 58 increased, 57 decreased and 17 had direction conflicts.
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).
Based on meta-analyses showing tryptophan's role in depression and serotonin pathways. Evidence comes from studies of tryptophan depletion and kynurenine pathway research rather than direct supplementation RCTs. Conservative effectiveness due to indirect evidence.
AI-estimated from published studies. Interpret as directional guidance.
Tryptophan has a higher evidence score (5.5/10 vs 7.8/10) and wins in 2 of 3 categories.
For support mood, St. John's Wort has a higher relevance score (92 vs 75).
Caution: Risk of serotonin syndrome: agitation, tremor, hyperthermia, tachycardia Do not combine without medical supervision Always consult a healthcare provider before combining these supplements.
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The right pick depends on your goals. Answer a few quick questions for a personalised recommendation — or dig into the full evidence on each.