Black pepper (piperine) — interactions

The reason piperine is in supplement stacks is exactly the reason it is on this page: it inhibits CYP3A4 and P-glycoprotein, so it raises the blood level of whatever it is sold alongside. "Enhanced bioavailability" and "drug interaction" are the same sentence read from two directions.

Also known as: piperine, Piper nigrum, long pepper, BioPerine. Category: seasoning.

What it does, mechanism by mechanism

CYP3A4 inhibition — inhibits, moderate

Slows the enzyme that metabolises roughly half of all prescription drugs. A CYP3A4 substrate taken with a CYP3A4 inhibitor reaches higher blood levels than its dose implies.

Volak et al. characterise piperine as a relatively SELECTIVE CYP3A4 inhibitor among the common spice constituents. Shoba et al. measured a 20-fold increase in curcumin bioavailability in humans from 20 mg piperine.

Sources: Bhardwaj RK 2002, Volak LP 2008, Shoba G 1998 · more on CYP3A4 inhibition

P-glycoprotein inhibition — inhibits, moderate

Blocks the efflux pump that ejects drugs back into the gut lumen and out of the brain. Raises absorption of P-gp substrates like digoxin, and can raise brain exposure independently of blood level.

Sources: Bhardwaj RK 2002 · more on P-glycoprotein inhibition

What it reaches in this dataset

Via CYP3A4 inhibition

Via P-glycoprotein inhibition

This list is what is IN the table. It is not the set of substances this interacts with — that set is larger and partly unknown, and the mechanism is the thing to carry to a substance we have not listed.

Specific combinations

What a clean result means here

A clean result means NO DOCUMENTED INTERACTION IN THIS DATASET. It does not mean safe, and it is not a clearance. Most substances are not in this dataset at all, and for many pairs that are, nobody has ever studied the combination.

In this dataset

  • Monoamine oxidase inhibition (prescription MAOIs, RIMAs, linezolid, methylene blue, harmala alkaloids)
  • Serotonergic drugs and the serotonin-toxicity mechanism
  • Dietary tyramine and L-dopa loads
  • The major cytochrome P450 pathways: CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 — inhibition and induction
  • P-glycoprotein inhibition and induction
  • 11β-HSD2 inhibition (the licorice mechanism) and the potassium consequences that follow it
  • QT prolongation as an additive pharmacodynamic axis
  • Culinary seasonings and common foods with documented pharmacological activity
  • A selected set of narrow-therapeutic-index drugs where those shifts matter most

Not in this dataset

  • Any substance not named in this dataset — which is most substances. There are tens of thousands of marketed drugs and this table holds fewer than a hundred entries.
  • Phase-2 conjugation (UGT, SULT, NAT2, COMT) except where a specific entry names it. The oilahuasca corpus turns heavily on phase 2 and this engine models it only in passing.
  • Pharmacogenomics. CYP2D6 and CYP2C19 are strongly polymorphic; a poor metaboliser and an ultra-rapid metaboliser can have opposite outcomes from the same pair, and this engine does not know your genotype.
  • Dose, timing, duration, formulation and route — all of which change whether a documented interaction is clinically real for you.
  • Renal and hepatic impairment, age, pregnancy, and body composition.
  • Additive sedation, respiratory depression, bleeding risk, hypoglycaemia and most other pharmacodynamic axes beyond the ones listed above.
  • Herb–herb interactions outside the named entries, and essentially the whole botanical world: most plants have no interaction literature at all.
  • Allergy, intolerance, and contamination or adulteration of unregulated products.
  • Anything published after the last-reviewed date below.

72 substances, 20 mechanisms, 64 citations. Last reviewed . Primary literature (every DOI resolved against the Crossref API) and FDA drug labelling. There is no free, openly-licensed, comprehensive drug-interaction dataset to draw on; NLM retired its Drug Interaction API on 2024-01-02 and DrugBank's interaction set is a commercial licence.

References

  1. Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF (2002). Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4. The Journal of Pharmacology and Experimental Therapeutics. doi:10.1124/jpet.102.034728
  2. Volak LP, Ghirmai S, Cashman JR, Court MH (2008). Curcuminoids Inhibit Multiple Human Cytochromes P450, UDP-Glucuronosyltransferase, and Sulfotransferase Enzymes, whereas Piperine is a Relatively Selective CYP3A4 Inhibitor. Drug Metabolism and Disposition. doi:10.1124/dmd.108.020552
  3. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PSSR (1998). Influence of Piperine on the Pharmacokinetics of Curcumin in Animals and Human Volunteers. Planta Medica. doi:10.1055/s-2006-957450

Every DOI above was resolved against the Crossref API on 2026-09-09 and the returned title checked against the one printed here. Three DOIs in the first draft resolved to real but different papers and were corrected before publication.

Last reviewed . All interaction pages.