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Saffron vs St. John's Wort for mood: which has better evidence?

A tie on evidence grade for mood (Saffron Grade B vs St. John's Wort Grade B). For mood, the two are evidence-matched; the difference is in effect and safety.

Reviewed by Substrate editorial, Independent research collective ·

Platform evidence comparison

These existing platform assessments are separate from the source-reported findings below. They do not represent a direct trial comparing these treatments.

SaffronSt. John's Wort
Gradegrade Bgrade B
Certaintymoderatemoderate
Effectmultiple RCTs show benefit for mild-to-moderate depressive symptoms, comparable to low-dose SSRIs in small trialseffective for mild-to-moderate depression in trials
Studied dose30 mg/day300 mg ×3/day
Populationadults with mild-moderate depressionadults, mild-to-moderate depression
Safety0 modeled interaction(s)1 modeled interaction(s)
Grade
B
what does the grade mean?
Certainty
moderate
what does certainty mean?

Grade B / moderate: probably helps, and new studies are unlikely to reverse this — but could shrink the effect size.

Direct comparison evidence

There are no direct RCTs in our corpus comparing Saffron and St. John's Wort head-to-head for mood. What we present above is an indirect comparison: each side's own trials, contrasted. This is standard practice for supplement comparisons — dose, population, and outcome-instrument differences between the two evidence bases add uncertainty on top of each side's own grade.

Can you take both?

No modeled interaction between Saffron and St. John's Wort in our corpus. Absence of a recorded interaction is not proof of additive benefit — combined-effect trials are usually absent for supplement pairs, so treat "stack" claims skeptically.

Decision guidance

sources: PMID:34757208 · PMID:18843608 · PMID:27589952

Grade history

No grade changes yet. Initial grade assigned; re-reviewed on every 12 months (Grade A/B) — next review by . Methodology v1.

Re-review cadence: every 12 months (Grade A/B) · next scheduled by · methodology v1.

Frequently asked

Which has stronger evidence: Saffron or St. John's Wort for mood?

Saffron carries Grade B at moderate certainty; St. John's Wort carries Grade B at moderate. The stronger evidence points to a tie, subject to the caveat that direct head-to-head trials are usually absent for supplement pairings.

Can I take Saffron and St. John's Wort together?

No modeled interaction between Saffron and St. John's Wort; combining is not documented to be problematic, but combined-effect trials are also absent, so treat additive benefit claims skeptically.

Have Saffron and St. John's Wort been compared head-to-head?

Direct RCTs comparing the two for mood are uncommon. This page contrasts each side's own trial evidence — that is an indirect comparison, which introduces confounds from population and dose differences. See the direct-comparison block above.

What decides between Saffron and St. John's Wort for me?

Read the decision guidance below — the split usually comes down to population fit, interaction risk with your other medications, and how much certainty you want behind the recommendation.

Related

Cite this page

Citation is encouraged. The proposed reuse license is CC-BY-4.0; status: pending-governance-ratification.

Plain-text citation
Substrate. Saffron vs St. John's Wort for mood. https://evidencebased.info/compare/saffron-vs-st-johns-wort-for-mood. Updated 2026-07-14.
BibTeX
@misc{substrate_vsstjohnswortformood,
  author = {Substrate editorial},
  title  = {Saffron vs St. John's Wort for mood},
  year   = {2026},
  url    = {https://evidencebased.info/compare/saffron-vs-st-johns-wort-for-mood},
  note   = {evidencebased.info}
}