Piperine (Bioperine)

Overview

Piperine is the pungent alkaloid of black pepper, and Bioperine is a trademarked black pepper extract that supplement makers use as a source of piperine. In small human studies, piperine raised blood levels of curcumin, propranolol, theophylline and phenytoin (PMIDs 9619120, 1815977, 16767797). It also interacts with prescription medicines, most clearly phenytoin, so anyone on medication should ask a clinician first. The human studies are small, and none of the ones read for this page tested piperine with NMN or NR, so the pairing is untested.

What is Piperine (Bioperine)?

Key takeaways

• Piperine raised blood levels of propranolol and theophylline in a 1991 crossover of six volunteers per group, given 20 mg a day for seven days (Bano et al., PMID 1815977).
• Adding 20 mg of piperine raised phenytoin levels on a second study day in 20 patients on steady-state dosing (Pattanaik et al., 2006, PMID 16767797).
• A 1998 study reported a 2,000% rise in curcumin bioavailability with 20 mg of piperine. Its abstract does not give the volunteer count (Shoba et al., PMID 9619120).
• In a randomized trial of 23 adults, piperine raised brain blood flow during tasks when taken with resveratrol, but plasma resveratrol did not change (Wightman et al., 2014, PMID 24804871).
• Lab work points both ways. In 2002, piperine blocked P-glycoprotein and CYP3A4 in cell and liver-microsome tests (PMID 12130727). In 2013, it activated the receptor that turns CYP3A4 on in human cells (PMID 23707768).
• The MAV NMN + NR serving lists 50 mg of Bioperine extract. The product page does not state the piperine share, so that dose cannot yet be placed against the 20 mg studied amount.
• No record read for this page tested piperine with NMN, NR or TMG.

Piperine is an alkaloid, a nitrogen-containing plant compound. Chemically it is the trans-trans isomer of 1-piperoyl-piperidine (Sharma et al., 2010, PMID 20525733), with the formula C17H19NO3. It is the pungent alkaloid that gives black pepper its bite (Tripathi et al., 2025, PMID 41053306). Long pepper carries it too (Hu et al., 2005, PMID 15916450).

Bioperine is the trade name for a black pepper extract. The MAV product page lists it as "Bioperine (Piper nigrum fruit)" and states that Bioperine is a registered trademark of Sabinsa Corporation. Keep that in mind when you read the trials. A 2025 randomized trial of a piperine-containing blend lists authors affiliated with Sabinsa companies (Majeed et al., PMID 41305713).

Piperine does not clear quickly. A 2026 review reports that piperine is metabolized after intake and can remain in circulation for extended periods (Huang et al., PMID 42186276). The studies read for this page did not report a half-life for piperine itself.

Most human work does not study piperine alone. It tests piperine as an add-on for another compound, usually at a fixed milligram amount. The studies read for this page did not test it with NMN or NR. Our NAD+ guide explains the pathway both ingredients feed.

Black pepper in food is not the same as a capsule, and the food evidence is thin. In a 2001 crossover, six healthy volunteers took a 300 mg phenytoin tablet 30 minutes after a soup with or without black pepper. The pepper soup raised phenytoin absorption and slowed its clearance (Velpandian et al., 2001, PMID 11808866). The abstract does not give the piperine content of the soup.

The number people repeat most is 2,000 percent. It comes from a 1998 study in which curcumin alone left blood levels undetectable or very low in healthy volunteers, while curcumin with 20 mg of piperine produced much higher levels (Shoba et al., 1998, PMID 9619120). The authors reported a 2,000 percent rise in bioavailability (PMID 9619120). That figure describes one compound at one curcumin dose, in a group whose size the abstract does not give. It is not a general multiplier for other ingredients.

The 2025 blend data shows that the piperine share matters. In an open-label trial of 14 healthy volunteers, curcumin with 1 percent piperine reached a peak concentration (Cmax) of 10.94 ng/mL. Curcumin with 10 percent piperine reached 663.60 ng/mL, comparable with the 647.97 ng/mL of a separate turmeric extract (Malhotra et al., 2025, PMID 41426786). Several authors list Nisarga Biotech as an affiliation, which readers should weigh when reading that comparison.

How it works

The most-studied mechanism is inhibition of two drug-handling systems. P-glycoprotein (P-gp) is a pump that pushes many drugs back out of gut cells. CYP3A4 is an enzyme that breaks down a large share of prescription drugs in the liver and gut wall. In cell and liver-microsome tests, piperine inhibited P-gp transport of digoxin and cyclosporine A, with IC50 values of 15.5 and 74.1 µM. It also inhibited CYP3A4 formation of two verapamil metabolites, with Ki values of 36 to 77 µM (Bhardwaj et al., 2002, PMID 12130727, DOI 10.1124/jpet.102.034728). These are lab results. They show a plausible mechanism, not a measured change in a person.

The opposite direction also appears in the lab, and the mouse data point the same way as the cells. Wang and colleagues found that piperine activated the human pregnane X receptor (PXR). That raised CYP3A4 and MDR1 (the gene for P-gp) expression in human hepatocytes and intestinal cells, and in a mouse model (Wang et al., 2013, PMID 23707768). The authors say this runs against the enzyme inhibition reported earlier, and they urge caution with piperine during drug treatment. The two lab findings do not agree on direction.

Shoba and colleagues describe piperine as a known inhibitor of glucuronidation in the liver and intestine, the conjugation step that tags many compounds for clearance. They used that idea to explain why curcumin is poorly absorbed and why piperine helped (Shoba et al., 1998, PMID 9619120). That is a proposed mechanism for the curcumin result, not a demonstrated one.

The resveratrol trial shows the effect is not about blood levels. Piperine did not change plasma resveratrol, yet it raised frontal blood flow during tasks when taken with resveratrol. The authors describe a gain in bioefficacy without a change in bioavailability (Wightman et al., 2014, PMID 24804871). Blood flow is a physiological measure. The same trial found no change in cognition, mood or blood pressure.

Review articles add more proposed mechanisms, including changes in intestinal permeability and interference with first-pass metabolism. Tripathi and colleagues call for rigorous clinical trials before those mechanisms can be relied on (Tripathi et al., 2025, PMID 41053306). Piperine is not alone in this. Quercetin, which has its own monograph, modulates P-gp in lab studies, and some flavonols stimulate P-gp-mediated efflux (Zhou et al., 2004, PMID 15072439).

Evidence at a glance

What the evidence doesn't support yet

Five claims outrun the data.

The 2,000 percent figure is not a general multiplier. It came from one 1998 curcumin study, and its abstract gives no volunteer count. No record read for this page reports a similar rise for NMN, NR, zinc or TMG.

Piperine does not reliably switch CYP3A4 down. The 2002 inhibition came from cell and liver microsome tests, not from people. The 2013 cell and mouse work found the opposite direction, with more CYP3A4 and MDR1 expression. No human record read here settles which effect dominates in a person, and none measured CYP3A4 activity in people.

Piperine did not raise plasma resveratrol in the 2014 trial. The gain was in brain blood flow during tasks, in 23 adults given single doses, with no change in cognition or mood.

Black pepper did not add to turmeric's pain effect in a 2026 crossover of 30 adults: pain fell in every arm, and the arm differences were not statistically significant.

No record read for this page tests piperine together with NMN or NR, in people or in animals, so the pairing is an open question. Two records pair piperine with nicotinamide in a formula, which is a different molecule. One is a 2025 mouse study of a five-ingredient formula, and the other a trial protocol with no results yet (Wimer et al., PMID 41086114; Tanwar et al., PMID 42026060). The pairing with NMN or NR is untested.

Related reading

• Resveratrol, the compound in the 2014 brain blood flow trial

Clinical evidence

• Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation — 23 adults took placebo, 250 mg trans-resveratrol, or resveratrol with 20 mg piperine on separate days in a double-blind crossover. Frontal blood flow during tasks rose with the pair compared with placebo and with resveratrol alone. Cognition, mood and blood pressure did not change. Plasma resveratrol did not differ between treatments in a separate group of six. Limitation: single doses, 23 people, and blood flow is not a clinical outcome.
• A Randomized, Controlled, Phase III Clinical Trial to Evaluate the Efficacy and Tolerability of Risorine with Conventional Rifampicin in the Treatment of Newly Diagnosed Pulmonary Tuberculosis Patients — 216 patients with newly diagnosed sputum-positive pulmonary tuberculosis were randomized to standard therapy (117) or a fixed-dose combination of rifampicin 200 mg, isoniazid 300 mg and piperine 10 mg (99). Sputum conversion at 4 weeks was 93% vs 84%. Cure at 24 weeks was 92% vs 82%. Liver-enzyme elevations occurred in 3 patients vs 9. Limitation: the combination changes several things at once, so piperine's own effect cannot be separated, and completion was 75% vs 79%.
• Effect of rifampin with bio-enhancer in the treatment of newly diagnosed sputum positive pulmonary tuberculosis patients: A double-center study — Randomized, parallel-group, two-centre study. 63 patients completed. The piperine arm used rifampicin 200 mg, isoniazid 300 mg and piperine 10 mg, against usual care with rifampicin 450 mg. Sputum conversion was faster and liver-enzyme rises were smaller in the piperine arm. Adverse drug events were reported by 22.2% vs 36.8%. Limitation: small, and the arms differ in more than piperine.
• Bioenhancer Assessment of Black Pepper with Turmeric on Self-Reported Pain Ratings in Adults: A Randomized, Cross-Over, Clinical Trial — 30 adults aged 40 and older with moderate chronic pain took part in a randomized crossover over 21 days, texting pain ratings three times a day. Arms compared turmeric alone with turmeric plus black pepper, at three turmeric amounts. Pain fell from baseline to week 3 in all arms, and between-arm differences were not statistically significant. Limitation: food-level pepper, short trial, self-reported pain only.
• An Open Label, Randomized, Comparative Bioavailability Study of BioTurm Extract Versus Curcuma longa Extract With Piperine in Healthy Adult Volunteers — 14 healthy volunteers, 4 to 5 per arm, took a single oral dose of a proprietary turmeric extract, curcumin 95% with 1% piperine, or curcumin 95% with 10% piperine. Peak concentration (Cmax) was 647.97 ng/mL for the extract, 10.94 ng/mL with 1% piperine, and 663.60 ng/mL with 10% piperine. Limitation: 14 people, single dose, and several authors list the extract maker as an affiliation.
• Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers — Healthy volunteers took 2 g curcumin alone or with 20 mg piperine. Curcumin serum levels were undetectable or very low alone and much higher from 0.25 to 1 hour with piperine. The authors report a 2000% rise in bioavailability and no adverse effects. Rats showed a 154% rise. Limitation: the abstract gives no volunteer count, design or blinding detail.
• Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers — Six subjects per group, crossover. Single oral doses of propranolol 40 mg or theophylline 150 mg were given alone or with piperine 20 mg daily for 7 days. With piperine, propranolol peaked sooner with higher peak level and AUC. Theophylline showed higher peak level, longer half-life and higher AUC. Limitation: small groups and no placebo arm.
• Effect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy — 20 patients with uncontrolled epilepsy on steady-state phenytoin (two groups of 10, given 150 mg or 200 mg twice daily). On one study day they took phenytoin alone; on the next, phenytoin with 20 mg piperine. Piperine raised AUC (0 to 12 h), peak level and absorption rate. Elimination rate and time to peak did not change significantly. Limitation: no randomization and no placebo day.
• Piperine in food: interference in the pharmacokinetics of phenytoin — Six healthy volunteers, crossover design. A 300 mg phenytoin tablet was taken 30 minutes after a soup with or without black pepper. Pepper increased phenytoin absorption rate and AUC and delayed elimination. The abstract gives no piperine content for the soup. The same paper includes mouse and rat work. Limitation: six people, food rather than an extract, and no piperine dose.
• Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4 — Piperine inhibited digoxin and cyclosporine A transport across Caco-2 monolayers (IC50 15.5 and 74.1 µM) and inhibited CYP3A4 formation of two verapamil metabolites in human liver microsomes (Ki 36 to 77 µM). Limitation: cells and microsomes, not people. The authors call the human phenytoin and rifampin reports preliminary and say dietary piperine could affect substrate levels in people.
• Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1 — Piperine activated human PXR and raised CYP3A4 and MDR1 expression in human hepatocytes and intestinal cells, and in a mouse model. Piperine bound the PXR ligand-binding domain in a competitive assay. The authors say the induction runs opposite to reported enzyme inhibition and advise caution during drug treatment. Limitation: cells and a mouse model, no human dosing.

Dosage & forms

• Black pepper extract (Bioperine) capsules:
• Piperine stated as a milligram amount:
• Whole black pepper in food:
• Multi-ingredient capsules with piperine added:
• Prescribed fixed-dose combination with rifampicin:

Safety & interactions

How much to take

The human studies that used a set dose mostly used 20 mg of piperine. Patel and colleagues used 10 mg in a fixed-dose tuberculosis combination (2017). Combination trials of blends used 3.75 to 10 mg a day (Askari et al., 2026, PMID 42021338; Alikiaii et al., 2025, PMID 40514680; Majeed et al., 2025, PMID 41305713). That is the studied range. The human studies read here did not report a piperine dose above 20 mg, so this page cannot say where more piperine stops helping or starts causing harm.

Timing has not been compared. Single-dose studies saw changes within about an hour (Shoba et al., 1998, PMID 9619120). The 1991 study ran seven days of daily piperine, and the 2017 tuberculosis trial ran for 24 weeks. The abstracts read here do not compare timing with meals, with fasting, or at bedtime, so no timing advice is given.

A label that gives only an extract weight does not show the piperine dose. Check the label for piperine in milligrams, not just the extract weight, and ask the brand for that number if it is missing.

No upper limit appeared in the records read for this page. The 2025 review describes dose-dependent toxicity but gives no number in its abstract (Tripathi et al., 2025, PMID 41053306). No overdose pattern was reported in the records read.

Safety profile

In the human trials read here, adverse events were few or not reported. Shoba and colleagues reported no adverse effects with 20 mg of piperine given with curcumin (PMID 9619120). Wightman and colleagues found no change in mood, cognition or blood pressure at 20 mg with resveratrol (PMID 24804871). These trials were small and short, and none was built to catch rare harms, so the absence of reports is not proof of safety.

The tuberculosis trials are harder to read. Patel and colleagues reported liver-enzyme rises in 3 patients on the piperine combination and 9 on standard therapy (PMID 29313577). Nageswari and colleagues reported adverse drug events in 22.2% of the piperine arm and 36.8% of usual care (PMID 31720402). Both trials gave whole regimens, so these numbers cannot be assigned to piperine alone.

Liver injury needs its own note. A 2021 review assessed a small number of liver-injury reports with curcumin products that also contained piperine, using the RUCAM causality method. The authors suggest piperine itself could contribute and say human trials are needed to settle the question (Stati et al., 2021, PMID 34776989).

Reproduction is not settled. Tripathi and colleagues list reproductive concerns but do not give the data in the abstract (PMID 41053306). The records read for this page include no human pregnancy or breastfeeding study. The pregnancy-search records read were animal studies and unrelated work.

Who should ask a clinician first

Ask a clinician or pharmacist before use if you:

• take phenytoin or another anticonvulsant
• take rifampicin or any other medicine for tuberculosis
• take propranolol, theophylline, cyclosporine, digoxin, verapamil, or another drug cleared through CYP3A4 or P-glycoprotein
• are pregnant, planning a pregnancy, or breastfeeding
• have a liver condition
• are considering a piperine product for a child, since no child-specific data were read

Drug and product interactions

If you take any prescription medicine, ask your prescriber or pharmacist before you add a piperine product, and bring the label with you.

Buying guide

The dose that matches the research

The studies used 10 to 20 mg of piperine. A label that gives only an extract weight does not show that amount. Ask for the piperine share, or the piperine milligrams, before you compare a product with the studies. Without that number, the dose cannot be matched.

The form on the label

Look for Bioperine, piperine, black pepper extract, or Piper nigrum. Bioperine is a registered trademark of Sabinsa Corporation, so the trade name alone does not describe the material. Check whether the label states piperine in milligrams, and whether the amount is for the extract or for the active compound.

Proof of testing

Ask for the lot-specific certificate of analysis and read the test list. If a label names piperine, the certificate should show a piperine test. The lot certificate linked from the NMN + NR product page lists NMN, NR, resveratrol, TMG and zinc. It has no piperine or Bioperine line (checked October 20, 2026). Our label-check guide walks through the same checks on any bottle.

Price per day

Price per day is the fair comparison. The Mt. Angel NMN + NR capsule lists 50 mg of Bioperine extract per two-capsule serving, with 30 servings per container. On the live product page (checked October 20, 2026), that works out to $2.00 a day. The price does not tell you the piperine dose, so use it only after the first two checks above, which cover the dose and the label form. See the label and today's price. For a wider view of NMN and NR labels, see our NMN and NR buying guide.

Red flags

• A blend that lists piperine or black pepper extract with no milligram amount.
• A "clinically proven" line with no study named.
• A piperine amount far above the 10 to 20 mg used in studies, since no record read for this page tested a higher amount.
• No lot certificate, or a certificate with no test for an ingredient the label names.

Bottom line. If you take any prescription medicine, ask a clinician before you add piperine, especially with phenytoin or rifampicin. If you are checking a label, look for piperine in milligrams rather than an extract weight, and check the lot certificate for a piperine test. No record read for this page tested piperine with NMN or NR, so a label cannot show that the pair works better together.

Related reading

• The 1998 study that linked piperine to curcumin absorption
• How black pepper became an absorption story, 1985 to 2025

Frequently Asked Questions

What is piperine and where does Bioperine come from?

Piperine is an alkaloid, a nitrogen-containing compound found in black pepper (Piper nigrum) and long pepper (Piper longum). Its formula is C17H19NO3. Bioperine is the trade name of a black pepper extract, and the MAV product page says it is a registered trademark of Sabinsa Corporation. Pepper is a seasoning. The extract is a concentrated supplement ingredient, and most human trials used a set milligram amount of piperine, not the seasoning.

Does piperine increase absorption of other ingredients, and how well is that shown?

In small human studies, yes, for some compounds. Piperine at 20 mg raised blood levels of curcumin, propranolol, theophylline and phenytoin (PMIDs 9619120, 1815977, 16767797). Piperine did not raise plasma resveratrol in a 23-person trial (PMID 24804871), although it changed brain blood flow when taken with resveratrol. Most of these studies were small, single-dose or short, and open-label, so the evidence is preliminary. No record read for this page tested piperine with NMN or NR.

Which medicines can piperine affect?

The clearest human evidence involves phenytoin. Piperine raised phenytoin levels in 20 patients on steady dosing (PMID 16767797), and pepper soup raised them in six volunteers (PMID 11808866). Piperine also raised propranolol and theophylline levels in a 1991 crossover of six per group (PMID 1815977). Rifampicin is used with piperine in a prescribed fixed-dose combination in trials. Lab work also points to CYP3A4 and P-glycoprotein, two systems that handle many prescription drugs in the body. Ask your prescriber before you combine any piperine product with a prescription, and ask the pharmacist to check the piperine amount against your medicine list.

How much piperine is in our serving and how does that compare with the studied doses?

The MAV NMN + NR serving lists 50 mg of Bioperine black pepper extract in two capsules. The product page does not state the piperine share, so the piperine amount is not known. Most single-compound studies used 20 mg of piperine, while the 2017 combination trial used 10 mg of it alongside rifampicin and isoniazid. Until the piperine share is stated, the serving cannot be placed in the studied range. The lot certificate linked from the product page has no piperine test.

Who should ask a clinician before taking a product with piperine?

Anyone taking a prescription medicine should ask first. The drugs most in question are phenytoin, rifampicin and other tuberculosis medicines, propranolol, theophylline, and drugs cleared through CYP3A4 or P-glycoprotein. Pregnant or breastfeeding people should ask too, because a 2025 review lists reproductive concerns without giving human data. People with a liver condition should ask as well, since a 2021 review assessed a small number of liver-injury reports with curcumin products that also contained piperine. Bring the label to that conversation.

How can a reader check whether a label lists black pepper extract?

Read the Supplement Facts panel and the other ingredients line. Look for Bioperine, piperine, black pepper extract, or Piper nigrum on the ingredient list, not only on the front of the bottle. A Bioperine line should show an amount in milligrams. The piperine share, if stated, is the number that matters for comparison. If the label gives only a blend total or a proprietary blend, ask the brand for the piperine milligrams and the lot certificate.

Does black pepper extract help NMN or NR work better?

No record read for this page tested piperine with NMN or NR. The records that pair piperine with nicotinamide involve a different molecule. One is a 2025 mouse study of a five-ingredient formula that included nicotinamide and piperine, given to mice rather than people. The other is a trial protocol with no results yet. So the pairing has not been tested, and no study in this review shows that the two work better together. The [NMN and NR dose comparison](/health/nad-longevity-complete-guide/nmn-nr-doses-vs-the-trials) covers the amounts used in the NMN and NR trials.

Is black pepper in food the same as a piperine capsule?

Not clearly. One 2001 study found that a soup with black pepper raised phenytoin absorption in six volunteers (PMID 11808866), so food pepper can have an effect. That study did not report how much piperine the soup held. Capsules with a stated piperine amount let you compare directly with the 20 mg used in most studies. A seasoning amount cannot be turned into a studied dose from that study.

Do I need piperine at all?

No. This page found no daily requirement for piperine. Its main relevance is as an additive that changes how other compounds are absorbed or cleared. If you take a prescription, that effect is the reason to ask first. If a supplement you already take lists piperine, check whether the amount is stated and whether your clinician knows you take it.