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

A tie on evidence grade for mood (St. John's Wort Grade B vs Vitamin C Grade —). For mood, St. John's Wort has the stronger evidence grade.

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.

St. John's WortVitamin C
Gradegrade Bstudied, no effect
Certaintymoderatemoderate
Effecteffective for mild-to-moderate depression in trialsNot recommended for unipolar depression
Studied dose300 mg ×3/day—
Populationadults, mild-to-moderate depression—
Safety1 modeled interaction(s)0 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 St. John's Wort and Vitamin C 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 St. John's Wort and Vitamin C 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:18843608 · PMID:27589952 · PMID:35311615

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: St. John's Wort or Vitamin C for mood?

St. John's Wort carries Grade B at moderate certainty; Vitamin C carries Grade — 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 St. John's Wort and Vitamin C together?

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

Have St. John's Wort and Vitamin C 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 St. John's Wort and Vitamin C 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. St. John's Wort vs Vitamin C for mood. https://evidencebased.info/compare/st-johns-wort-vs-vitamin-c-for-mood. Updated 2026-07-14.
BibTeX
@misc{substrate_ortvsvitamincformood,
  author = {Substrate editorial},
  title  = {St. John's Wort vs Vitamin C for mood},
  year   = {2026},
  url    = {https://evidencebased.info/compare/st-johns-wort-vs-vitamin-c-for-mood},
  note   = {evidencebased.info}
}