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Head-to-head evidence comparison — which supplement is right for you?
Saffron vs St. John's Wort: Saffron has the stronger overall evidence (7.5 vs 7.8/10); 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.
Saffron wins 2 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Likely helps
5 of 5 studies with measurable effects showed benefit.
Top outcomes
Verdict
Likely helps
6 of 8 studies with measurable effects showed benefit.
Top outcomes
Shared outcomes (2)
Outcomes where both Saffron and St. John's Wort have evidence — compare verdict strength side-by-side.
28-30mg daily
Morning or split AM/PM
Affron® 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 21 more not shown
4-8 weeks
4-8 weeks
2 menstrual cycles
4-6 weeks
4-8 weeks
During use
First 1-2 weeks
Comparative efficacy and tolerability of nutraceuticals for depressive disorder: A systematic review and network meta-analysis
Psychological medicine (2025) · Meta analysis · n=17437
Hundred and ninety-two trials involving 17,437 patients and 44 nutraceuticals were eligible for inclusion.
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 eligible randomized controlled trials were included, covering 6599 stroke patients and evaluating nine different plant extract treatments, one of which was Crocus sativus (saffron).
New horizons for the study of saffron (Crocus sativus L.) and its active ingredients in the management of neurological and psychiatric disorders: A systematic review of clinical evidence and mechanisms
Phytotherapy research : PTR (2024) · Systematic review
A random-effects or fixed-effects model was used to calculate the pooled effect sizes.
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 are doses of a standardised saffron extract (affron) in adults with low mood. A 4-week RCT in 128 adults (PMID 28735826) gave 22 or 28 mg a day: mood improved at 28 mg (POMS total mood disturbance versus placebo, d = -1.10) with no effect at 22 mg. A 12-week RCT in 202 adults with subclinical depressive symptoms (PMID 40414301) confirmed a smaller benefit at 28 mg (DASS-21 depression, d = 0.39). Doses above 28 mg were not compared with lower ones in these trials, so no optimal dose or safety ceiling is plotted. The cited depression meta-analyses pool trials without comparing doses.
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.
Saffron has a higher evidence score (7.5/10 vs 7.8/10) and wins in 2 of 3 categories.
For support mood, St. John's Wort has a higher relevance score (92 vs 90).
No documented interaction was found in the data searched. This does not establish that this exact combination is safe.
Saffron, EPA omega-3, SAMe have real adjunct evidence — but these aren’t a substitute for care, and some interact dangerously.
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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.