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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
3 of 3 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 Agmatine and St. John's Wort have evidence — compare verdict strength side-by-side.
500-2500mg daily
Empty stomach for mood/nootropic effects, Pre-workout for pumps, Before bed for neuroprotection
Agmatine Sulfate
300mg 3x daily (900mg total)
With meals, Divided into 2-3 doses
Standardized extract (0.3% hypericin)
2-4 weeks
1-2 weeks
Ongoing
Acute
4-6 weeks
4-8 weeks
During use
First 1-2 weeks
Exploring the Cardiovascular Impacts of Agmatine: A Systematic Review
Medical sciences (Basel, Switzerland) (2025) · Systematic review
The effects exerted by AG depend on the dose and route of administration, as well as on the receptors involved and the pathophysiological pathway used.
Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets
Cells (2024) · Systematic review
Together, neuroinflammation and gut dysbiosis induce alterations in tryptophan metabolism, culminating in decreased serotonin synthesis, impairments in neuroplasticity-related mechanisms, and glutamate-mediated excitotoxicity.
Role of agmatine in neurodegenerative diseases and epilepsy
Frontiers in bioscience (Elite edition) (2014) · Systematic review
Agmatine, a cationic polyamine synthesized after decarboxylation of L-arginine by the enzyme arginine decarboxylase, is an endogenous neuromodulator that emerges as a potential agent to manage diverse central nervous system (CNS) disorders.
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.
Based on single pilot study (n=11) showing 46% pain reduction. Very limited evidence with small sample size. GI discomfort may occur at higher doses. Individual variation noted in study.
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 (7.8/10 vs 4/10) and wins in 2 of 3 categories.
For support mood, St. John's Wort has a higher relevance score (92 vs 65).
No known interactions between Agmatine and St. John's Wort have been documented in our database. However, always consult a healthcare provider before combining supplements.