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Head-to-head evidence comparison — which supplement is right for you?
Agmatine vs St. John's Wort: St. John's Wort has the stronger overall evidence (7.8 vs 4/10); they're alternatives for support mood — the best pick depends on your goals. 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
Mostly mechanism / observational
Top outcomes
Verdict
Likely helps
6 of 8 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) (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)
and 21 more not shown
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
Systematic review of 60 preclinical studies on agmatine and the heart and blood vessels, searched in PubMed, Cochrane and Embase.
Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets
Cells (2024) · 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) · 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
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.
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 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 documented interaction was found in the data searched. This does not establish that this exact combination is safe.
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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.