Loading…
We use essential cookies (authentication, your saved goals/stack) by default. With your permission we’ll also enable privacy-respecting analytics (Vercel Web Analytics, anonymous load-time metrics) and error-replay diagnostics (Sentry — DOM snapshots only when an error fires) so we can fix bugs faster. Learn more about cookies
Head-to-head evidence comparison — which supplement is right for you?
Huperzine A vs St. John's Wort: St. John's Wort has the stronger overall evidence (7.8 vs 6/10); 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
Too few graded studies
1 of 2 studies with measurable effects showed benefit.
Top outcomes
Verdict
Likely helps
6 of 8 studies with measurable effects showed benefit.
Top outcomes
Shared outcomes (1)
Outcomes where both Huperzine A and St. John's Wort have evidence — compare verdict strength side-by-side.
50-200mcg twice daily
Morning and early afternoon, Avoid evening (may cause vivid dreams)
Huperzine A capsules (standardized extract)
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 1 more not shown
and 21 more not shown
2-4 weeks
30-60 minutes
2-4 weeks
During use
4-6 weeks
4-8 weeks
During use
First 1-2 weeks
The treatment of cognitive dysfunction in dementia: a multiple treatments meta-analysis
Psychopharmacology (2018) · Meta analysis · n=44854
The pooled standardized mean difference of the treatment effects on cognitive dysfunction was 0.439 (95% confidence interval 0.374, 0.504).
Traditional Chinese herbal medicine for vascular dementia
The Cochrane database of systematic reviews (2018) · Systematic review · n=3581
Two TCHMs (NaoMaiTai and TongXinLuo) had a 5% or more increased risk of AEs compared to the 'no Treatment' control, but the quality of this evidence was poor.
Interventions to delay functional decline in people with dementia: a systematic review of systematic reviews
BMJ open (2016) · Systematic review · n=70
The quality of the reviews varied; however most (65%) scored 8/11 or more on the AMSTAR tool, indicating high quality.
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.
Doses are per day. At 200 mcg (0.1 mg twice daily), a double-blind trial in 78 people with mild to moderate vascular dementia improved MMSE, CDR and daily living scores over 12 weeks (PMID 21833673). At 400 mcg (200 mcg twice daily), the primary analysis of a phase II trial in 210 people with Alzheimer's disease found no effect on ADAS-Cog at 16 weeks, so the curve stays flat rather than rising (PMID 21502597). At 800 mcg (400 mcg twice daily), the same trial found a 2.27-point ADAS-Cog gain at 11 weeks that was no longer significant at 16 weeks. A meta-analysis of four trials using 300 to 500 mcg a day found MMSE and daily living gains (PMID 19221692). The trials are in different populations and only one compared doses, so no minimum, optimal or safe ceiling is set.
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 6/10) and wins in 2 of 3 categories.
No documented interaction was found in the data searched. This does not establish that this exact combination is safe.
Which supplements clash with blood thinners, thyroid meds, antibiotics & more — and what to do.
Saffron, EPA omega-3, SAMe have real adjunct evidence — but these aren’t a substitute for care, and some interact dangerously.
What’s safe while nursing, the truth about milk-supply herbs, and what to avoid (it passes into milk).
The right pick depends on your goals. Answer a few quick questions for a personalised recommendation — or dig into the full evidence on each.