Black pepper extract and piperine

What it is

Piperine is the main pungent compound of black pepper (Piper nigrum). In supplements it is added as a standardised black pepper extract, usually in milligram amounts, mainly to increase the absorption of other ingredients such as curcumin.

What the research says

Piperine does raise blood levels of other substances: in one small human study it raised curcumin absorption about 20-fold. It does this by blocking the gut and liver systems that clear drugs and foreign compounds, including the CYP3A4 enzyme and the P-glycoprotein pump (shown in cell and liver-tissue experiments). The same mechanism means it can raise levels of prescription drugs, and piperine-boosted turmeric products appear in liver injury case series. Direct human interaction evidence is mixed. Trials of curcumin-piperine combinations report improvements in inflammatory and metabolic markers, but they are small and short.

Evidence grade: Limited evidence.

What goes wrong

In human intestinal cells and human liver microsomes, piperine inhibited both the P-glycoprotein drug pump and the CYP3A4 drug-metabolising enzyme, which the authors said could raise blood levels of orally taken drugs. (Source 1)

• Lab study in cells, Low certainty.
• Size: Caco-2 cell monolayers and 2 human liver microsome samples.
• Who: Not applicable (laboratory)
• How long: Not applicable.
• Result: Digoxin transport IC50 15.5 microM; cyclosporine A IC50 74.1 microM.
• Funding: not stated.

Because both proteins are expressed in enterocytes and hepatocytes and contribute to a major extent to first-pass elimination of many drugs, our data indicate that dietary piperine could affect plasma concentrations of P-glycoprotein and CYP3A4 substrates in humans, in particular if these drugs are administered orally.

The same paper cites earlier human data showing piperine raised blood levels of the drugs phenytoin and rifampin. (Source 1)

• Lab study in cells, Low certainty.
• Size: Not stated (cited prior studies)
• Who: Humans in earlier cited studies.
• How long: Not stated.
• Result: Not stated.
• Funding: not stated.

Preliminary data indicate that piperine, a major component of black pepper, inhibits drug-metabolizing enzymes in rodents and increases plasma concentrations of several drugs, including P-glycoprotein substrates (phenytoin and rifampin) in humans.

In the US DILIN turmeric liver injury series, 3 of the 7 products chemically tested also contained piperine, and the authors suggested increased combination with black pepper may explain rising cases. (Source 2)

• Case series, Low certainty.
• Size: 10 cases; 7 products tested.
• Who: Adults with turmeric-associated liver injury.
• How long: 2004-2022.
• Result: 3 of 7 tested products contained piperine.
• Funding: not stated.

Chemical analysis confirmed the presence of turmeric in all 7 products tested; 3 also contained piperine (black pepper).

NIH LiverTox (a position) states that high-bioavailability curcumin products, made using piperine or nanoparticle delivery, were linked to liver injury cases and an Italian outbreak of hepatitis. (Source 3)

• Official position, Certainty not rated.
• Size: Not applicable.
• Who: People taking high-bioavailability curcumin.
• How long: Not applicable.
• Result: Qualitative.
• Funding: independent (NIH)

These high bioavailability forms of purified curcumin were subsequently linked to several cases of liver injury and mentioned as a possible cause of outbreaks of acute hepatitis with jaundice in Italy.

What the evidence supports

In healthy volunteers, adding 20 mg piperine to 2 g curcumin increased curcumin bioavailability by 2000% compared with curcumin alone. (Source 4)

• Randomized trial, Low certainty.
• Size: Small group of healthy human volunteers (plus rats)
• Who: Healthy adult volunteers.
• How long: Single dose.
• Result: Bioavailability increase 2000% in humans; 154% in rats.
• Funding: not stated.

Limit of this finding: The 2000% figure comes from the human arm of this 1998 study, which gave a small group of healthy volunteers a single 2 g dose of curcumin with a flat 20 mg of piperine. The rat arm of the same paper used a different dosing convention (20 mg/kg of piperine) and found a much smaller increase, 154%. Read the 2000% as one single-dose result in a small volunteer group, not as a general multiplier for curcumin supplements.

Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%.

A systematic review of curcumin-piperine trials - counted as 20 in its abstract and 19 in its results section - found most of them reported lower inflammatory markers, but the trials were small (8 to 117 people) and short (1 to 12 weeks). (Source 5)

• Systematic review, Low certainty.
• Size: About 20 RCTs (the review states 20 in its abstract and 19 in its results), 8-117 participants each.
• Who: Adults with inflammatory, metabolic, cardiovascular and other conditions.
• How long: 1 to 12 weeks.
• Result: 15 of the trials reported significant decreases in CRP, hs-CRP or IL-6 (the review describes this as 15 of 20 in the abstract and 15 of 19 in the results); piperine doses 5-15 mg/day.
• Funding: not stated.

Limit of this finding: This review does not agree with itself on how many trials it included: the abstract says 20 randomised trials, while its results section says 19. Its own risk-of-bias tally in the quoted passage (13 low risk plus 6 with moderate issues) adds up to 19, not 20. Treat the trial count as roughly twenty and unsettled; nothing else in the finding depends on which number is right.

There were 20 RCTs with sample sizes ranging from 8 to 117 individuals and durations ranging from 1 to 12 weeks.

What the evidence does not support

In trials summarised by the same review, curcumin-piperine did not change the handling of the probe drugs midazolam, flurbiprofen or paracetamol, and in at least one trial had no effect on BMI, LDL, HDL, insulin or blood pressure. (Source 5)

• Systematic review, Low certainty.
• Size: Individual trials within the review (about 20 RCTs)
• Who: Adults (trial-specific)
• How long: 1 to 12 weeks.
• Result: No change reported (table entries)
• Funding: not stated.

Limit of this finding: This review does not agree with itself on how many trials it included: the abstract says 20 randomised trials, while its results section says 19. Its own risk-of-bias tally in the quoted passage (13 low risk plus 6 with moderate issues) adds up to 19, not 20. Treat the trial count as roughly twenty and unsettled; nothing else in the finding depends on which number is right.

no change in pharmacokinetics of midazolam, flurbiprofen, paracetamol

Where the research disagrees

Whether piperine meaningfully changes drug levels in people

• Bhardwaj et al., J Pharmacol Exp Ther 2002, Cell and human liver microsome experiments: In summary, we showed that piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4. (Source 1)
• Trial summarised in Pan et al., Frontiers in Nutrition 2026, Human trial within a systematic review: no change in pharmacokinetics of midazolam, flurbiprofen, paracetamol (Source 5)

How much

• Reference intake: No recommended intake exists; piperine is not an essential nutrient. None was identified in the sources reviewed. (Source 1)
• Upper limit: No tolerable upper limit for piperine was found in the sources reviewed. (Source 5)
• Studied: Curcumin-piperine trials gave 5-15 mg/day piperine with 500-1,500 mg/day curcumin. (Source 5)
• Studied: A single-dose human pharmacokinetic study gave 20 mg piperine with 2 g curcumin. (Source 4)

A common belief, and what the research shows

The belief: Black pepper extract is just a harmless absorption helper.

What the research shows: It works by blocking the body's drug-clearing systems. Bhardwaj et al. found 'piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4', and DILIN found piperine in 3 of 7 tested turmeric products linked to liver injury.

Questions and answers

What is it?

Piperine is the main pungent compound in black pepper. Supplements add it as a black pepper extract, usually to boost absorption of another ingredient. (Source 1)

What does it do in the body?

It slows how the gut and liver clear compounds, which raises blood levels of other substances. In one human study it raised curcumin absorption about 20-fold. (Source 4)

Is it good or bad for you?

Pepper as a seasoning has no established harm. In supplements, its absorption boost is also its risk: it can raise levels of medicines handled by CYP3A4 and P-glycoprotein, and piperine-containing turmeric products appear in liver injury reports. (Source 1)

How do you get more of it?

It comes from black pepper in food, or from standardised black pepper extract in supplements, where trials used 5-15 mg a day. (Source 5)

If it is harmful, what reduces it?

Its effect on drug clearance applies while it is being taken; in turmeric-related liver injury, reported cases generally recovered after the product was stopped. No study specifically of removing piperine was found. (Source 3)

Why might someone be low in it or missing it?

Does not apply. Piperine is not an essential nutrient, and no deficiency state is described in the literature we searched. (Source 1)

We searched: Europe PMC abstracts on piperine pharmacology and curcumin-piperine trials; no deficiency state described.

Which whole foods contain it or feed it?

Black pepper is the food source of piperine. (Source 1)

What happens if you do not have it?

Nothing is known to happen; piperine is not essential. Without it, curcumin taken by mouth is barely absorbed. (Source 4)

How can you test for it?

No clinical test for piperine levels exists in the literature we searched. (Source 1)

We searched: Europe PMC and web search for piperine pharmacology, curcumin-piperine trials and piperine measurement; only research pharmacokinetic methods found.

References

1. The Journal of Pharmacology and Experimental Therapeutics. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. 2002. PMID 12130727, DOI 10.1124/jpet.102.034728. Read the source
2. The American Journal of Medicine. Liver Injury Associated with Turmeric-A Growing Problem: Ten Cases from the Drug-Induced Liver Injury Network [DILIN]. 2023. PMID 36252717, DOI 10.1016/j.amjmed.2022.09.026. Read the source
3. National Institute of Diabetes and Digestive and Kidney Diseases (NCBI Bookshelf). Turmeric - LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2025. Read the source
4. Planta Medica. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. 1998. PMID 9619120, DOI 10.1055/s-2006-957450. Read the source
5. Frontiers in Nutrition. Curcumin-piperine supplementation modulates inflammation, oxidative stress, and cardiometabolic risk: a systematic review of randomized controlled trials. 2026. PMID 42232574, DOI 10.3389/fnut.2026.1814168. Read the source