NutriStack
Berberine and Simvastatin, a caution.
Simvastatin is strongly affected by CYP3A4 inhibitors, and berberine has human evidence of inhibiting CYP3A4 activity with repeated dosing. This may increase simvastatin exposure and muscle toxicity risk, although direct clinical trials of this exact supplement-drug pair are lacking. Risk is higher with higher simvastatin doses or additional interacting medications.
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
- Berberine and Simvastatin
- Pair type
- Caution
- Evidence (highest tier)
- Emerging
- Source citations
- 3 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Emerging evidence
Caution
What is happening. Simvastatin is strongly affected by CYP3A4 inhibitors, and berberine has human evidence of inhibiting CYP3A4 activity with repeated dosing. This may increase simvastatin exposure and muscle toxicity risk, although direct clinical trials of this exact supplement-drug pair are lacking. Risk is higher with higher simvastatin doses or additional interacting medications.
Mechanism. Berberine can inhibit CYP3A4 activity in humans. Simvastatin is extensively metabolized by CYP3A4, so inhibition can increase systemic exposure to simvastatin and simvastatin acid.
Recommendation. Avoid high-dose berberine with simvastatin unless your prescriber has reviewed the interaction risk. Stop and seek care promptly for severe muscle pain, weakness, or dark urine.
Sources (3)
- Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-217. PMID 21870106
- Feng P, Zhao L, Guo F, Zhang B, Fang L, Zhan G, et al. The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins. Chem Biol Interact. 2018;293:115-123. PMID 30086269
- Hirota T, Fujita Y, Ieiri I. An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol. 2020;16(9):809-822. PMID 32729746
Stack Score
How this pair moves the number.
Effect on the composite score
If both Berberine and Simvastatin are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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