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Head-to-head evidence comparison — which supplement is right for you?
Vitamin D3 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
Probably helps
15 of 26 studies with measurable effects showed benefit.
Top outcomes
Shared outcomes (1)
Outcomes where both St. John's Wort and Vitamin D3 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)
2000-4000 IU daily
Morning with breakfast
D3 (cholecalciferol) softgel or liquid
May reduce vitamin D effectiveness and serum 25(OH)D levels
Monitor vitamin D status if using St. Johns Wort long-term.
4-6 weeks
4-8 weeks
During use
First 1-2 weeks
4-8 weeks
4-8 weeks
2-4 weeks
4-8 weeks
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.
Vitamin D supplementation vs. placebo and incident type 2 diabetes in an ancillary study of the randomized Vitamin D and Omega-3 Trial
Nature communications (2025) · Meta analysis · n=5205
Mean body mass index (BMI) was 27.5 kg/m2 (SD = 5.3), with 51% female and 17% Black race/ethnicity.
Vitamin D Supplementation for Patients with Dysmenorrhoea: A Meta-Analysis with Trial Sequential Analysis of Randomised Controlled Trials
Nutrients (2024) · Meta analysis · n=687
TSA revealed that the current RCTs provide sufficient information.
Vitamin D and respiratory tract infections
BMJ (2017) · Meta analysis · n=11321
12% reduction in respiratory infections overall
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).
Meta-analysis showed 12% overall reduction in respiratory infections, with greater benefits in severely deficient individuals. Daily dosing more effective than bolus. Conservative estimate assumes most users not severely deficient.
AI-estimated from published studies. Interpret as directional guidance.
Vitamin D3 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 75).
May reduce vitamin D effectiveness and serum 25(OH)D levels Monitor vitamin D status if using St. Johns Wort long-term. Consult a healthcare provider for personalized advice.