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Head-to-head evidence comparison — which supplement is right for you?
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 7 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 5-HTP and St. John's Wort have evidence — compare verdict strength side-by-side.
50-100mg for sleep; 150-300mg for mood
For sleep: 30-45 minutes before bed, For mood: 2-3 divided doses with meals
Capsules
300mg 3x daily (900mg total)
With meals, Divided into 2-3 doses
Standardized extract (0.3% hypericin)
2-4 weeks
1-2 weeks
2-4 weeks
First 1-2 weeks
4-6 weeks
4-8 weeks
During use
First 1-2 weeks
Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD)
The Cochrane database of systematic reviews (2022) · Systematic review · n=2023
This review provides uncertain evidence only regarding the use of hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare formula, Oxepa formula, or 5-hydroxytryptophan as universal PTSD prevention strategies.
Combination pharmacotherapy for the treatment of fibromyalgia in adults
The Cochrane database of systematic reviews (2018) · Systematic review · n=1474
Two studies only reported any primary outcomes of interest (patient-reported pain relief of 30%, or 50%, or greater).
The Impact of 5-Hydroxytryptophan Supplementation on Cognitive Function and Mood in Singapore Older Adults: A Randomized Controlled Trial
Nutrients (2025) · Rct · n=30
Results: A significant time effect was observed in the MoCA score, which was mainly explained by a significant increase in the 5-HTP group (week 0 vs. week 12: 26.6 ± 1.4 a.u. vs. 27.6 ± 1.4 a.u., p < 0.05).
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.
Limited evidence from small RCTs (n=30, n=166). Effectiveness constrained by mixed study populations and preliminary findings. Higher doses associated with increased nausea risk.
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.
St. John's Wort has a higher evidence score (9/10 vs 8.5/10) and wins in 2 of 3 categories.
For support mood, St. John's Wort has a higher relevance score (92 vs 75).
No known interactions between 5-HTP and St. John's Wort have been documented in our database. However, always consult a healthcare provider before combining supplements.