tuneTypical Dose
5–20 mg per day
Mineral
Piperine
Piperine (1-Piperoylpiperidine, from Piper nigrum)
Evidence TierBWADA NOT PROHIBITED
watchEffect Window
Acute pharmacokinetic effect (same-dose bioavailability enhancement). Standalone health benefits are negligible at supplemental doses.
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
Piperine is the main alkaloid in black pepper that alters intestinal transport and metabolism. It is used chiefly as a bioavailability enhancer, with curcumin as the clearest human example.
Human evidence for piperine is strongest for increasing curcumin exposure after co-administration. Its practical value comes with a trade-off: the same CYP3A and transport effects that enhance supplements can also raise drug exposure, as shown in healthy-volunteer midazolam data. Standalone thermogenic or metabolic benefits are much less convincing than its interaction profile.
Inhibits UDP-glucuronosyltransferases and CYP3A4 first-pass metabolism, preventing rapid clearance of co-administered compounds. Also inhibits intestinal P-glycoprotein efflux pump.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Increases curcumin bioavailability by 2000%
- Can alter exposure of co-administered drugs and supplements
- Inhibits glucuronidation and CYP3A4 first-pass metabolism
Secondary Outcomes
- Mild thermogenic effect at high doses
- Minor anti-inflammatory activity in vitro
Safety
Contraindications and Interactions
Contraindications
- Concurrent narrow-therapeutic-index medications without physician guidance
- Polypharmacy without medical review
Side effects
- GI burning and irritation
- Non-selective enhancement of drug absorption (interaction risk)
Interactions
- Phenytoin (increased levels)
- Propranolol (increased levels)
- Theophylline (increased levels)
- Rifampin (increased levels)
- Methotrexate (increased levels)
- Warfarin (increased levels)
- CYP3A4 substrates broadly
Avoid if
- Taking narrow-therapeutic-index prescription medications without dose adjustment
- Polypharmacy (elderly on multiple medications)
Evidence
Study-level References
piperine-SRC-001Acute pharmacokinetic study
Sourceopen_in_newShoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64(4):353-356. doi:10.1055/s-2006-957450. PMID:9619120.
Population: Healthy human volunteers in the pharmacokinetic arm, with parallel rat experiments.
Dose protocol: 20mg piperine + 2g curcumin, acute single-dose pharmacokinetic study
Key findings: Concomitant administration of piperine 20 mg with curcumin 2 g produced a 2000% increase in the bioavailability of curcumin in humans, with no adverse effects.
Notes: Landmark study establishing piperine as the gold-standard bioavailability enhancer.
Paper content
This is the classic human piperine study. Piperine meaningfully increased curcumin exposure after a single dose, but the evidence is about bioavailability enhancement, not piperine-as-therapy.
piperine-SRC-002Randomized placebo-controlled healthy-volunteer pharmacokinetic study
Sourceopen_in_newRezaee MM, Kazemi S, Kazemi MT, Gharooee S, Yazdani E, Gharooee H. The effect of piperine on midazolam plasma concentration in healthy volunteers, a research on the CYP3A-involving metabolism. Daru. 2014;22(1):8. PMID:24398010.
Population: Twenty healthy volunteers, 14 men and 6 women.
Dose protocol: Piperine 15 mg/day for 3 days before an oral midazolam challenge
Key findings: Piperine pretreatment increased midazolam exposure and reduced clearance in healthy volunteers.
Notes: Direct human interaction evidence. Important for medication safety framing.
Paper content
This healthy-volunteer study directly supports piperine's interaction risk. By increasing midazolam exposure after short pretreatment, it shows that piperine's enzyme effects are not limited to supplements like curcumin.