Piperine is an alkaloid found in black pepper that's partially responsible for black pepper's spicy taste. Piperine is sold as BioPerine for use in increasing the bio-availability of other substances.

Natural Sources

The common spice black pepper (Piper nigrum) contains approximately 10% piperine along with up to 5% piperidine. Piperine is also found in 2 species of long pepper (Piper longum and Piper officinarum) at 1-2%.


Piperine sold under the name BioPerine has a typical dosage recommendation of up to 15 mg daily in 3 doses of 5 mg each distributed evenly throughout the day. Some BioPerine is sold as 10 mg tablets with instructions giving a maximum of 20 mg (2 tablets) per day.

Ground black pepper has been used in doses of up to 8 grams, with 2 grams being to usual maximum dose. 2 grams of black pepper at up to 10% piperine contains up to 200 mg of piperine. The piperine present in black pepper absorbs more slowly than pure piperine because of being present in a biological matrix. For this reason, black pepper produces a slower onset of the effects from piperine, with the overall duration extended, and the potency decreased. This makes it difficult to compare piperine dosage to black pepper dosage since pure piperine absorbs faster, which increases its potency.

Using Black Pepper Medicinally

To use black pepper for its piperine content efficiently the black pepper should be consumed whole in capsules, and not brewed as filtered tea.

Doses of up to 8 grams of black pepper have been used orally. However, if brewed as filtered tea, you would need at least 8 1/2 cups of water to hold this level of piperine. Piperine's solubility in water is extremely low (40 mg/L @18 C). 1 cup of water at @18 C can only hold up to 9.4 mg of piperine, the amount of piperine in about 94 mg of black pepper.

Effects On Enzymes

Piperine is commonly used as a bio-availability enhancer. Concomitant administration of 20 mg piperine taken orally with curcumin was proven to enhance the bio-availability of curcumin by up to 2000%.[11]

Piperine inhibits several enzymes in humans and also induces some.

Piperine exhibits it's inhibition effects on enzymes typically after about 15 minutes, with it's primary enzyme inhibition usually lasting from 1-2 hours, or even longer in some cases.

Pretreatment of piperine by 15 minutes is recommended when used to enhance the bio-availability of other supplements via enzyme inhibition.

While black pepper is also used in herbal remedies as a bio-availability enhancer, because if it's high piperine content. It's important to note that piperine's effects in black pepper have a slower onset and are weaker because the piperine in black pepper is trapped within a biological matrix, requiring some level of digestion to occur before the piperine is liberated and available to perform it's action.

MAO Inhibition

Piperine inhibits rat MAO-A in a dose-dependent manner with an IC50 value of 49.3 microM. It inhibits MAO-B in a dose-dependent manner with an IC50 of 91.3 microM.[8]

Tests showing significant MAO-A and MAO-B enzyme inhibition in humans are currently lacking. Anecdotal reports indicate that MAO-A and MAO-B enzyme inhibition in humans is ineffective at normal doses.

Effects On the Cytochrome P450 Enzyme System

Effects In Humans In Vivo

Studies in human test subjects provide evidence of piperine potently inhibiting CYP3A4. Studies also give evidence that it inhibits CYP2E1 and may inhibit CYP2C19, and CYP2D6. It's effect on CYP1A2 and CYP2C9 are unclear.

Cytochrome P450 enzyme Presumed effects based on test results in humans
CYP1A2 possible inhibition and/or induction
CYP2C19 possible inhibition
CYP2C9 possible inhibition
CYP2D6 possible inhibition
CYP2E1 potent inhibition
CYP3A4 potent inhibition

One study on humans found that 20 mg piperine, taken for 10 days, inhibited CYP2E1 metabolism of chlorzoxazone.[13]

Piperine, at 15 mg orally, taken 3 days in a row, caused a 184% increase in the duration of the effects of a 10 mg oral dose of midazolam. Midazolam is primarily a substrate of CYP3A4. The study supports the action of piperine as a potent inhibitor of CYP3A4.[9] Another test using carbamazepine as a CYP3A4 substrate found that piperine increased carbamazepine activity, suggesting CYP3A4 inhibition.[15]

In humans 20 mg of piperine was found to enhance systemic availability of 40 mg propranolol or 150 mg theophylline.[2] Propanolol is a substrate of CYP1A2, CYP2C19, and CYP2D6 in humans. Because theophylline is a primary substrate of CYP1A2 in humans, this indicates possible inhibition of CYP1A2 by piperine in humans.

In another set of tests performed on human subjects using caffeine as a CYP1A2 substrate, piperine actually increased caffeine clearance, strongly indicating that piperine may actually induce CYP1A2 rather than inhibit it.[10]

Conflicting results exist for CYP2C9. Some tests performed in humans found that piperine had no effect on flurbiprofen, a CYP2C9 substrate, at doses up to 24 mg.[6] Other tests using diclofenac sodium as a CYP2C9 substrate found that 20 mg of piperine significantly enhanced the effects of diclofenac sodium suggesting potential inhibition of CYP2C9 by piperine.[14]

Effects On Human Liver In Vitro

One in vitro test found piperine to be a potent selective inhibitor of CYP3A4 (IC50 5.5 μM) with some effect on CYP1A2 (IC50 29.8 μM) and CYP2C9 (IC50 40.7 μM), and almost no effect on CYP2B6, CYP2C19, CYP2D6, and CYP2E1.[7]

Effects In Mice In Vivo

Piperine was found to improve activity of docetaxel by inhibiting CYP3A4 in vivo in mice.[4]

Effects In Rats In Vivo

In rats in vivo, piperine induced CYP1A (by 15%), CYP2B1 and CYP2B2, and inhibited CYP2E1 by 28-30% (as evident by alteration in 4-Nitrophenol and aniline hyroxylase activity).[1]

Effects on Glucuronosyltransferase (UGT)

Piperine is speculated to inhibit UGT enzymes in humans. Note that searching the PubMed database for tests confirming this action on UGT enzymes in humans has yielded no results. If such studies proving this action in humans isn't just speculation please leave a comment on this page using the discuss link.

In humans, piperine was proven to enhance the bio-availability of curcumin by as much as 20 times.[11] It's believed that inhibition of UGT by piperine is responsible for this ability to increase the potency of curcumin in humans.

Piperine enhances bio-availability of EGCG in mice in vivo. Piperine appeared to increase EGCG bio-availability by inhibiting UGT and gastrointestinal transit.[5]

Effects on Other Enzymes

Piperine was found to inhibit arylhydrocarbon hydroxylase and 7-ethoxycourmarin deethylase in rats. [3]


LD50 data has been gathered from tests on animals. Most animals given a lethal dose died of respiratory paralysis within 3-17 minutes.[12]

route adult male mice LD50 adult female rats LD50
i.v. 15.1 mg/kg[12]
i.p. 43 mg/kg[12] 33.5 mg/kg[12]
s.c. 200 mg/kg[12]
i.g. (oral) 330 mg/kg[12] 514 mg/kg[12]
i.m. 400 mg/kg[12]

No known LD50 exists for humans. Based on a 330 mg/kg oral LD50 for rats, we can roughly estimate that a lethal oral dose in a 75 kg (165 pound) adult human could be approximately 24,750 mg. That's a dose that's over 1000 times the typical 20 mg adult dose of piperine used to increase the bio-availability of curcumin by 2000%.

Black pepper is not known to be toxic in humans. Black pepper doses of up to 8 grams are reported in the literature. 8 grams of black pepper can contain up to 800 mg of piperine, although black pepper's piperine is weaker and has a slower onset because it takes considerable time for the body to extract the piperine from black pepper's biological matrix. Black pepper doses of 2 grams are more typically used. Such a dose would contain up to 200 mg of piperine.

Documented overdoses in humans using pure piperine could not be found, but it's likely possible to overdose on pure piperine if several grams of piperine are ingested. Considering the amounts of piperine present in 2 grams of black pepper, it's unlikely that doses up to 200 mg of piperine would cause toxicity. However, no documented cases of humans ingesting such an amount of pure piperine could be located. If a verified known overdose of black pepper or piperine exists, please leave a comment on this page via the Discuss link at the bottom of this page.

Chemical Structure

Piperine is composed of a 1-(1-Oxobut-2-enyl)piperidine molecule connected to a slightly modified safrole molecule.

Safrole Piperine
safrole.gif piperine.png

Chemical Properties

Although piperine is an alkaloid, it's only able to form salts with very strong acids. For example, a salt such as piperine citrate is not possible, because citric acid is not a strong enough acid to form a salt with piperine. Even hydrochloric acid is not strong enough to form a stable salt with piperine. Piperine hydrochloride is practically insoluble in water because it decomposes into hydrochloric acid and piperine on contact with water.

Synonyms: 1-Piperoyl-piperidine
Cas number: 94-62-2
PubChem Compound ID: 638024
Molecular Weight: 285.33766 [g/mol]
Molecular Formula: C17H19NO3
XLogP3: 3.5
IUPAC Name: (2E,4E)-5-(1,3-benzodioxol-5-yl)-1-piperidin-1-ylpenta-2,4-dien-1-one
InChI: InChI=1S/C17H19NO3/c19-17(18-10-4-1-5-11-18)7-3-2-6-14-8-9-15-16(12-14)21-13-20-15/h2-3,6-9,12H,1,4-5,10-11,13H2/b6-2+,7-3+
Canonical SMILES: C1CCN(CC1)C(=O)C=CC=CC2=CC3=C(C=C2)OCO3
Isomeric SMILES: C1CCN(CC1)C(=O)/C=C/C=C/C2=CC3=C(C=C2)OCO3
Physical state: Solid white or light-green crystals.
Boiling Point: Decomposes.
Melting Point: 130°C (266°F)
Specific Gravity: 1.193 (Water = 1)
Solubility: Very slightly soluble in cold water; Water solubility: 40 mg/L (18 C);
Soluble in 30 parts of alcohol at 15° C. (59° F.), in 1 part of boiling alcohol; Slightly soluble in ether;

1. Xenobiotica. 1994 Dec;24(12):1195-204.
Piperine effects on the expression of P4502E1, P4502B and P4501A in rat. Kang MH, Won SM, Park SS, Kim SG, Novak RF, Kim ND; College of Pharmacy, Seoul National University, Korea; PubMed PMID: 7771106
2. Eur J Clin Pharmacol. 1991;41(6):615-7.
Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Bano G, Raina RK, Zutshi U, Bedi KL, Johri RK, Sharma SC; Department of Pharmacology and Therapeutics, Government Medical College, Jammu-Tawi, India; PubMed PMID: 1815977
3. Indian J Exp Biol. 1991 Jun;29(6):568-73.
In vitro and in vivo inhibition of pulmonary cytochrome P450 activities by piperine, a major ingredient of piper species. Reen RK, Singh J; Biochemistry Section, Regional Research Laboratory, Jammu-Tawi, India. PubMed PMID: 1889831
4. Prostate. 2012 May 1;72(6):661-7. doi: 10.1002/pros.21469. Epub 2011 Jul 27.
Co-administration of piperine and docetaxel results in improved anti-tumor efficacy via inhibition of CYP3A4 activity. Makhov P, Golovine K, Canter D, Kutikov A, Simhan J, Corlew MM, Uzzo RG, Kolenko VM; Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA; PubMed PMID: 21796656
5. J Nutr. 2004 Aug;134(8):1948-52.
Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in mice. Lambert JD, Hong J, Kim DH, Mishin VM, Yang CS; Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey, Piscataway, NJ 08854, USA; PubMed PMID: 15284381; (Download Attached PDF Document)
6. Br J Clin Pharmacol. 2013 Feb;75(2):450-62. doi: 10.1111/j.1365-2125.2012.04364.x;
Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers; Volak LP, Hanley MJ, Masse G, Hazarika S, Harmatz JS, Badmaev V, Majeed M, Greenblatt DJ, Court MH; Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston; PubMed PMID: 22725836
7. Curcuminoids inhibit multiple human cytochromes P450 (CYP), UDP-glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes, while piperine is a relatively selective CYP3A4 inhibitor
Laurie P. Volak, Senait Ghirmai, John R. Cashman, and Michael H. Court PubMed PMC ID: PMC2574793
8. Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones.
Kong LD, Cheng CH, Tan RX. PubMed PMID: 15120460
9. The effect of piperine on midazolam plasma concentration in healthy volunteers, a research on the CYP3A-involving metabolism
Mohammad Mahdi Rezaee, Sohrab Kazemi, Mohammad Taghi Kazemi, Saeed Gharooee, Elham Yazdani, Hoda Gharooee, Mohammad Reza Shiran and Ali Akbar Moghadamnia; DARU Journal of Pharmaceutical Sciences 2014 22:8; DOI: 10.1186/2008-2231-22-8; PMID: 24398010; PMCID: PMC3904487
10. Effect of Piperine on Caffeine Salivary Concentration in Healthy Volunteers
A. Gholampour (MD), M. Hashemi (BSc), M.M. Rezaee (MD), M.R. Shiran (Pharm D, PhD), A.A. Moghadamnia (Pharm D, PhD); J Babol Univ Med Sci; 15(4); Jul 2013; pp: 12-21
11. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS.; Planta Med. 1998 May;64(4):353-6.; PMID: 9619120 DOI: 10.1055/s-2006-957450
12. Acute and subacute toxicity of piperine in mice, rats and hamsters.
Piyachaturawat P, Glinsukon T, Toskulkao C.; Toxicol Lett. 1983 May;16(3-4):351-9.; PMID: 6857729
13. Effect of piperine on CYP2E1 enzyme activity of chlorzoxazone in healthy volunteers.
Bedada SK, Boga PK. Xenobiotica. 2016 Sep 27:1-25. PMID: 27670974; DOI: 10.1080/00498254.2016.1241450
14. Study on influence of piperine treatment on the pharmacokinetics of diclofenac in healthy volunteers.
Bedada SK, Boga PK, Kotakonda HK. PMID: 27052193; DOI: 10.3109/00498254.2016.1163752
15. Effect of Piperine on the Metabolism and Pharmacokinetics of Carbamazepine in Healthy
Bedada SK, Appani R, Boga PK. PMID: [https://www.ncbi.nlm.nih.gov/pubmed/27776366 27776366 DOI: 10.1055/s-0042-118173
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