NutriStack
Rosuvastatin and St. John's Wort, a conflict.
St. John's Wort induces CYP3A4 and P-glycoprotein, which can reduce rosuvastatin levels. While rosuvastatin is less dependent on CYP3A4 than other statins, P-glycoprotein induction can still significantly reduce its bioavailability, potentially compromising cholesterol management.
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At a glance
- Substances
- Rosuvastatin and St. John's Wort
- Pair type
- Conflict
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −10 to your Stack Score (per scored conflict row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Conflict · Moderate evidence
Conflict
What is happening. St. John's Wort induces CYP3A4 and P-glycoprotein, which can reduce rosuvastatin levels. While rosuvastatin is less dependent on CYP3A4 than other statins, P-glycoprotein induction can still significantly reduce its bioavailability, potentially compromising cholesterol management.
Mechanism. St. John's Wort upregulates P-glycoprotein (MDR1) via PXR activation. Rosuvastatin is a P-glycoprotein substrate for intestinal efflux. Increased P-gp activity reduces rosuvastatin intestinal absorption and increases biliary excretion, lowering plasma concentrations.
Recommendation. Avoid combining St. John's Wort with rosuvastatin. P-glycoprotein induction may reduce rosuvastatin absorption even though it is not primarily CYP3A4-metabolized.
Sources (2)
- Sugimoto K et al. Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther. 2001;70(6):518-524. PMID 11753267
- Kang Y, Park JM, Lee SH. Moderate-Intensity Rosuvastatin/Ezetimibe Combination versus Quadruple-Dose Rosuvastatin Monotherapy: A Meta-Analysis and Systemic Review. Yonsei Medical Journal. 2024. PMID 38154476
Stack Score
How this pair moves the number.
Effect on the composite score
If both Rosuvastatin 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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