NutriStack
Simvastatin and St. John's Wort, a conflict.
St. John's Wort dramatically reduces simvastatin levels through potent CYP3A4 induction. Simvastatin is highly dependent on CYP3A4 for metabolism, making this one of the most clinically significant statin-herb interactions. Simvastatin AUC may be reduced by over 50%.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Simvastatin and St. John's Wort
- Pair type
- Conflict
- Evidence (highest tier)
- Strong
- Source citations
- 1 source
- Stack Score effect
- −10 to your Stack Score (per scored conflict row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Conflict · Strong evidence
Conflict
What is happening. St. John's Wort dramatically reduces simvastatin levels through potent CYP3A4 induction. Simvastatin is highly dependent on CYP3A4 for metabolism, making this one of the most clinically significant statin-herb interactions. Simvastatin AUC may be reduced by over 50%.
Mechanism. Simvastatin is extensively metabolized by CYP3A4 as a first-pass effect. St. John's Wort's potent CYP3A4 induction via PXR activation dramatically increases simvastatin presystemic metabolism, reducing the amount of active drug reaching systemic circulation.
Recommendation. Do not combine St. John's Wort with simvastatin. This interaction can render simvastatin ineffective for cholesterol management. Discuss alternative mood support with your prescriber.
Stack Score
How this pair moves the number.
Effect on the composite score
If both Simvastatin and St. John's Wort are in the same stack, this pair applies −10 to your Stack Score (per scored conflict row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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