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Head-to-head evidence comparison — which supplement is right for you?
St. John's Wort vs Tryptophan: St. John's Wort has the stronger overall evidence (7.8 vs 5.5/10); take care combining them — there's a flagged interaction. Take the 60-second quiz for a pick tailored to your goals.
St. John's Wort wins 2 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Likely helps
6 of 8 studies with measurable effects showed benefit.
Top outcomes
Verdict
Likely helps
3 of 3 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) (a typical label dose, not the dose used in the cited trial, which gave 600 mg once a day or 600 mg twice a day)
With meals, Divided into 2-3 doses
Standardized extract (0.3% hypericin)
500-1000 mg before bed. The cited sleep meta-analysis found the benefit mainly at 1 g a day or more.
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
In nine larger placebo-controlled trials the combined response rate ratio was 1.28 (95% CI 1.10 to 1.49), and in nine smaller trials 1.87 (95% CI 1.22 to 2.87). Placebo-controlled results showed marked heterogeneity.
Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis
Neuropsychopharmacology reports (2025) · Meta analysis · n=1049
Eight RCTs, 1049 participants. St. John's Wort was analysed in two trials, both comparing it to fluoxetine.
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 · n=6599
48 RCTs covering 6599 stroke patients and nine plant extracts.
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
Hundred and ninety-two trials involving 17,437 patients and 44 nutraceuticals were eligible for inclusion.
Differential Metabolites in Osteoarthritis: A Systematic Review and Meta-Analysis
Nutrients (2023) · Meta analysis · n=495
A systematic review and meta-analysis of 13 studies with 495 participants comparing small-molecule metabolites in people with osteoarthritis against healthy people. No supplement was tested.
Both points come from one randomised, double-blind trial of the WS 5570 extract in 332 outpatients with mild or moderate major depression (PMID 16796730). Over 6 weeks, HAM-D scores fell 11.6 points on 600 mg once daily, 10.8 points on 600 mg twice daily and 6.0 points on placebo. Both doses beat placebo with comparable efficacy, so the curve is flat above 600 mg, although remission was more common at 1,200 mg. Adverse events were low in all groups. The Cochrane review (PMID 18843608, 29 trials) supports efficacy over placebo but did not compare doses, and no cited trial reports 300 mg, 900 mg or 1,800 mg a day, so no optimum is named.
AI-estimated from published studies. Interpret as directional guidance.
St. John's Wort has a higher evidence score (7.8/10 vs 5.5/10) 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.