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Head-to-head evidence comparison — which supplement is right for you?
Vitamin B12 wins 1 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
12 of 17 studies with measurable effects showed benefit.
Top outcomes
Shared outcomes (1)
Outcomes where both St. John's Wort and Vitamin B12 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)
500-1000mcg daily for maintenance; higher for deficiency
Morning (may be energizing), With or without food
Methylcobalamin (sublingual)
4-6 weeks
4-8 weeks
During use
First 1-2 weeks
2-4 weeks
4-8 weeks
Weeks to months
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.
Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis
Irish journal of medical science (2024) · Meta analysis · n=4275
Regarding the hemoglobin level, the pooled effect sizes showed no difference between all routes of administration that could reach statistical significance.
Dosage exploration of combined B-vitamin supplementation in stroke prevention: a meta-analysis and systematic review
The American journal of clinical nutrition (2024) · Meta analysis · n=76664
In areas without and with partial folic acid fortification, combined B-vitamin supplementation significantly reduced the risk of stroke by 34% [RR: 0.66; 95% confidence interval (CI): 0.50, 0.86] and 11% (RR: 0.89; 95% CI: 0.79, 1.00), respectively.
Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis
International journal of molecular sciences (2024) · Meta analysis · n=770
The effect sizes were expressed as standardised mean differences.
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.
Vitamin B12 has a higher evidence score (9/10 vs 9/10) and wins in 1 of 3 categories.
For support mood, St. John's Wort has a higher relevance score (92 vs 55).
No known interactions between St. John's Wort and Vitamin B12 have been documented in our database. However, always consult a healthcare provider before combining supplements.