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

St. John's Wort has the stronger evidence for mood (Creatine Grade C vs St. John's Wort Grade B). For mood, St. John's Wort has the stronger evidence grade.

Reviewed by Substrate editorial, Independent research collective ·

Head to head

CreatineSt. John's Wort
Gradegrade Cgrade B
Certaintylowmoderate
Effectemerging evidence as an adjunct for depressive symptoms; trials smalleffective for mild-to-moderate depression in trials
Studied dose3–5 g/day300 mg ×3/day
Populationadults with depressionadults, mild-to-moderate depression
Safety0 modeled interaction(s)1 modeled interaction(s)
Grade
C
what does the grade mean?
Certainty
low
what does certainty mean?

Grade C / low: hints of benefit in small trials; a well-run RCT could easily push this to B or to null.

Direct comparison evidence

There are no direct RCTs in our corpus comparing Creatine 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 Creatine 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:42180567

Grade history

No grade changes yet. Initial grade assigned; re-reviewed on every 6 months (Grade C+) — next review by . Methodology v1.

Re-review cadence: every 6 months (Grade C+) · next scheduled by · methodology v1.

Frequently asked

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

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

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

No modeled interaction between Creatine 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 Creatine 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 Creatine 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

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