NutriStack
Berberine and Diltiazem, a caution.
Diltiazem is itself a moderate CYP3A4 inhibitor that depends on the same enzyme for clearance. Adding berberine, which inhibits CYP3A4, CYP2D6, and CYP2C9 in humans, can raise diltiazem levels and amplify its negative chronotropic and vasodilatory effects. The result can be excessive bradycardia, hypotension, or AV block, particularly in older adults or those on other rate-slowing drugs.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. Diltiazem is itself a moderate CYP3A4 inhibitor that depends on the same enzyme for clearance. Adding berberine, which inhibits CYP3A4, CYP2D6, and CYP2C9 in humans, can raise diltiazem levels and amplify its negative chronotropic and vasodilatory effects. The result can be excessive bradycardia, hypotension, or AV block, particularly in older adults or those on other rate-slowing drugs.
Mechanism. Diltiazem is metabolized primarily by CYP3A4 to desacetyldiltiazem. Berberine's inhibition of CYP3A4 reduces both presystemic and hepatic clearance, increasing parent drug exposure and AV-nodal blockade.
Recommendation. Avoid combining berberine with diltiazem unless your prescriber agrees. If used together, check your pulse and blood pressure twice daily for 2 weeks after starting berberine and report a resting heart rate below 50 bpm, lightheadedness, or readings below your usual range.
Minimum separation. 240
Sources (2)
- 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):213-7. PMID 21870106
- Mills TA, Kawji MM, Cataldo VD, et al. Profound sinus bradycardia due to diltiazem, verapamil, and/or beta-adrenergic blocking drugs. J La State Med Soc. 2004;156(6):327-31. PMID 15688675
Stack Score
How this pair moves the number.
Effect on the composite score
If both Berberine and Diltiazem 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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