Black Pepper

In Ayurveda black pepper is one of the three spices of trikatu, a fine powder of ginger rhizome, long pepper and black pepper ^{32Reference 32Sharma et al. · 2022AnimalDeciphering the impact and mechanism of Trikatu, a spices-based formulation, on alcoholic liver disease employing network pharmacology analysis and in vivo validation — animal / in silicoView study →}. Trikatu and its herbs are used for fever, asthma, nasal and respiratory complaints, poor appetite, indigestion, obesity and skin conditions ^{32Reference 32Sharma et al. · 2022AnimalDeciphering the impact and mechanism of Trikatu, a spices-based formulation, on alcoholic liver disease employing network pharmacology analysis and in vivo validation — animal / in silicoView study →}.

Black pepper is also used as a stimulating expectorant, and it is applied externally for nasal congestion, sinusitis and inflamed skin ^{31Reference 31FernPiper nigrum — species database entry (habit, range, cultivation, uses)View study →}.

India has the most recorded traditional uses of the plant, mostly for menstrual and ear, nose and throat complaints in people and for digestive complaints in livestock. The fruit is usually taken as a powder, pill or paste ^{8Reference 8Takooree et al. · 2019Systematic reviewA systematic review on black pepper (Piper nigrum L.): from folk uses to pharmacological applications — systematic reviewView study →}.

In Chinese medicine black pepper is hu jiao ^{30Reference 30Tseng et al.Tseng, Y.-c., Xia, N., & Gilbert, M. G. (n.d.). Piper nigrum Linnaeus. In Wu, Z. Y., & Raven, P. H. (eds.), Flora of China, Vol. 4 — flora. http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200005581View study →}. It is used as a warming herb for stomach chills, food poisoning, dysentery, diarrhoea and vomiting caused by cold ^{31Reference 31FernPiper nigrum — species database entry (habit, range, cultivation, uses)View study →}.

In Western herbal medicine black pepper is taken for indigestion and wind, and it is regarded as a stimulating expectorant ^{31Reference 31FernPiper nigrum — species database entry (habit, range, cultivation, uses)View study →}.

In volunteers given 2 g of curcumin alone, blood levels were undetectable or very low. Adding 20 mg of piperine raised curcumin bioavailability by 2000%, with no adverse effects. In rats the same combination raised it by 154% ^{1Reference 1Shoba et al. · 1998Clinical trialInfluence of piperine on the pharmacokinetics of curcumin in animals and human volunteers — clinical trialView study →}.

In human intestinal Caco-2 cells, piperine inhibited P-glycoprotein transport of digoxin and cyclosporine. In human liver microsomes, it inhibited CYP3A4 ^{2Reference 2Bhardwaj et al. · 2002In vitroPiperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4 — in vitro (human microsomes, Caco-2)View study →}.

In rats, piperine given hours before curcumin raised curcumin exposure about sixfold, by temporarily reducing the liver and gut enzymes (UGTs and SULTs) that conjugate it. Given together at a 20:1 ratio, the increase was much smaller ^{3Reference 3Zeng et al. · 2017AnimalSelective reduction in the expression of UGTs and SULTs by which piperine enhances curcumin bioavailability — ratView study →}. In healthy volunteers, a curcumin product with 24 mg of piperine did not change how paracetamol was conjugated ^{36Reference 36Volak et al. · 2013Clinical trialEffect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers — clinical studyView study →}.

Piperine itself is absorbed rapidly across the gut wall, and it may help other molecules cross by changing membrane properties ^{5Reference 5Khajuria et al. · 1998Permeability characteristics of piperine on oral absorption — animalView study →}. In animal studies it also inhibits drug-metabolising enzymes in the liver and gut, including UDP-glucuronyl transferase ^{7Reference 7Srinivasan · 2007ReviewBlack pepper and its pungent principle-piperine: a review of diverse physiological effects — reviewView study →}.

In people, piperine has raised blood levels of phenytoin ^{35Reference 35Pattanaik et al. · 2006Clinical trialEffect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy — clinical studyView study →} and carbamazepine ^{34Reference 34Bedada et al. · 2017Clinical trialEffect of piperine on the metabolism and pharmacokinetics of carbamazepine in healthy volunteers — clinical studyView study →}, and short courses of isolated piperine have raised levels of several other drugs ^{6Reference 6Ziegenhagen et al. · 2021ReviewSafety aspects of the use of isolated piperine ingested as a bolus — reviewView study →}.

Gap: the effect is established for isolated piperine at defined doses. Its size depends on the drug, the dose ratio and the timing ^{3,4Reference 3Zeng et al. · 2017AnimalSelective reduction in the expression of UGTs and SULTs by which piperine enhances curcumin bioavailability — ratView study →Reference 4Han · 2011ReviewThe effects of black pepper on the intestinal absorption and hepatic metabolism of drugs — reviewView study →}.

Piperine suppresses the NF-κB inflammatory pathway in several models.

In fibroblast-like synoviocytes taken from 68 rheumatoid-arthritis patients, piperine reduced NF-κB activation, cell proliferation and inflammatory cytokines ^{10Reference 10Baito et al. · 2023Piperine suppresses inflammatory fibroblast-like synoviocytes from rheumatoid arthritis patients via NF-κB inhibition — ex vivo human cellsView study →}.

In mice, it reduced LPS-induced acute lung injury, with lower TNF-α, IL-6 and IL-1β and less NF-κB activation ^{11Reference 11Lu et al. · 2016AnimalPiperine ameliorates lipopolysaccharide-induced acute lung injury via modulating NF-κB signalling — mouse in vivoView study →}.

In microglia, it reduced inflammatory cytokines and PGE2, partly by activating the Nrf2/HO-1 pathway ^{12Reference 12Wang-Sheng et al. · 2017In vitroPiperine attenuates LPS-induced inflammatory responses in BV2 microglia — in vitroView study →}.

A meta-analysis of 13 trials of curcumin with piperine found lower TNF-α and IL-6 and less oxidative stress ^{20Reference 20Hosseini et al. · 2025Meta-analysisCurcumin plus piperine co-administration on inflammation and oxidative stress — systematic review and meta-analysis of randomised controlled trialsView study →}. The design cannot separate piperine’s contribution from curcumin’s.

Gap: no trial has tested piperine or pepper alone against an inflammatory outcome in people.

In a meta-analysis of trials in metabolic syndrome, curcumin with piperine lowered total and LDL cholesterol but did not change triglycerides ^{17Reference 17Hosseini et al. · 2023Meta-analysisCurcumin and piperine combination on lipid profile in metabolic syndrome — systematic review and meta-analysis of RCTsView study →}.

A larger 2025 analysis of 16 trials found lower triglycerides and total cholesterol and higher HDL, but no significant change in LDL ^{19Reference 19Karimi et al. · 2026Meta-analysisCurcuminoids plus piperine co-supplementation on serum lipid profile in adults — systematic review and meta-analysis of RCTsView study →}.

For blood sugar, a meta-analysis of 15 trials found a small fall in fasting glucose but no change in HbA1c, insulin or insulin resistance, and rated the evidence low in certainty ^{18Reference 18Karimi et al. · 2025Meta-analysisCurcumin plus piperine co-supplementation on glycemic control in adults — meta-analysis of randomised controlled trialsView study →}.

Piperine-only evidence is preclinical. In obese rats it reduced weight gain, insulin, glucose and liver fat ^{23Reference 23Wang et al. · 2022AnimalPiperine attenuates hepatic steatosis and insulin resistance in high-fat-diet-induced obesity — ratView study →}, and in cell and animal models it reduced fatty-acid absorption and repaired the gut barrier ^{22Reference 22Wang et al. · 2021Piperine improves obesity by inhibiting fatty-acid absorption and repairing intestinal barrier function — animal / cellView study →}.

Gap: the human data test the combination with curcumin and are inconsistent. Piperine’s own metabolic effect in people is unmeasured.

In a 1993 study, piperine protected mouse liver against tert-butyl hydroperoxide and carbon tetrachloride by reducing lipid peroxidation and preserving glutathione. It was less potent than silymarin ^{13Reference 13Koul et al. · 1993In vitroEvaluation of the liver protective potential of piperine — mouse in vivo / in vitroView study →}.

Later mouse studies extended this to thioacetamide-induced fibrosis, through miR-17 and TGF-β/Smad signalling ^{14Reference 14Abdelhamid et al. · 2021AnimalThe hepatoprotective effect of piperine against thioacetamide-induced liver fibrosis in mice — animal modelView study →}, and to paracetamol poisoning, where piperine worked best together with N-acetylcysteine ^{15Reference 15Coelho et al. · 2022AnimalPiperine as therapeutic agent in paracetamol-induced hepatotoxicity in mice — animal modelView study →}.

In a 12-week randomised trial in 70 people with fatty liver disease, 500 mg of curcuminoids with 5 mg of piperine daily improved disease severity on ultrasound compared with placebo. Liver enzymes fell within the treated group but did not differ significantly from placebo ^{16Reference 16Panahi et al. · 2019RCTCurcuminoids plus piperine improve nonalcoholic fatty liver disease — randomised controlled trialView study →}.

A meta-analysis of 18 trials of curcuminoids with piperine found lower AST and IL-6, while the fall in ALT was not significant overall ^{21Reference 21Karimi et al. · 2025Meta-analysisCurcuminoids plus piperine on liver enzymes and inflammation in adults — GRADE-assessed systematic review and meta-analysisView study →}.

Gap: every piperine-alone result is from animals.

Piperine scavenges free radicals in vitro. In UV-B-irradiated human skin cells, it reduced reactive oxygen species and inflammatory signalling ^{24Reference 24Jaisin et al. · 2020In vitroAntioxidant and anti-inflammatory effects of piperine on UV-B-irradiated human HaCaT keratinocytes — in vitroView study →}.

In microglia it activated the Nrf2/HO-1 antioxidant pathway ^{12Reference 12Wang-Sheng et al. · 2017In vitroPiperine attenuates LPS-induced inflammatory responses in BV2 microglia — in vitroView study →}, and it reduced lipid peroxidation in liver-injury models ^{13Reference 13Koul et al. · 1993In vitroEvaluation of the liver protective potential of piperine — mouse in vivo / in vitroView study →}.

Gap: no clinical antioxidant outcome has been measured, and dietary pepper has not been shown to change antioxidant status in people.

In cell and animal models, piperine reduced intestinal fatty-acid absorption by lowering FABP2 and CD36, and it strengthened the gut barrier ^{22Reference 22Wang et al. · 2021Piperine improves obesity by inhibiting fatty-acid absorption and repairing intestinal barrier function — animal / cellView study →}.

In obese rats, 27 mg/kg of piperine a day for 8 weeks lowered body weight by 5.7% and reduced liver fat and insulin resistance ^{23Reference 23Wang et al. · 2022AnimalPiperine attenuates hepatic steatosis and insulin resistance in high-fat-diet-induced obesity — ratView study →}.

Gap: no human trial has tested piperine or pepper alone for weight or body composition.

A systematic review of 40 preclinical studies found that piperine has antibacterial activity, inhibits bacterial efflux pumps and often strengthens antibiotics, mostly against Mycobacterium and Staphylococcus aureus ^{25Reference 25Murase et al. · 2023Systematic reviewAntibacterial and immunological properties of piperine evidenced by preclinical studies — systematic reviewView study →}.

A second review of eight studies found promising activity against Mycobacterium tuberculosis, mainly when piperine was combined with antituberculosis drugs ^{26Reference 26Hegeto et al. · 2019Systematic reviewPromising antituberculosis activity of piperine combined with antimicrobials — systematic reviewView study →}.

Gap: no clinical infection studies.

In microglia, piperine suppressed LPS-induced cytokines and PGE2 while activating Nrf2/HO-1 ^{12Reference 12Wang-Sheng et al. · 2017In vitroPiperine attenuates LPS-induced inflammatory responses in BV2 microglia — in vitroView study →}. A review collects animal data on cognition, mood and neurodegeneration ^{9Reference 9Haq et al. · 2021ReviewPiperine: a review of its biological effects — reviewView study →}.

Gap: no human neurological or cognitive trial of piperine or black pepper.

In cell lines and animal models, piperine slows cancer-cell growth and triggers cell death. In human ovarian cancer cells, it induced apoptosis through the JNK/p38 MAPK pathway without affecting normal ovarian cells ^{28Reference 28Si et al. · 2018In vitroPiperine functions as a tumour suppressor for human ovarian tumour growth via JNK/p38 MAPK-mediated apoptosis — in vitroView study →}. Reviews collect activity against breast, colon, prostate and other cancers ^{8,27Reference 8Takooree et al. · 2019Systematic reviewA systematic review on black pepper (Piper nigrum L.): from folk uses to pharmacological applications — systematic reviewView study →Reference 27Turrini et al. · 2020ReviewOverview of the anticancer potential of Piper nigrum and its main constituent piperine — reviewView study →}.

Gap: preclinical only. Human studies are missing ^{27Reference 27Turrini et al. · 2020ReviewOverview of the anticancer potential of Piper nigrum and its main constituent piperine — reviewView study →}.

Interactions. Piperine inhibits P-glycoprotein in the gut and CYP3A4 in the liver, both of which clear many drugs ^{2Reference 2Bhardwaj et al. · 2002In vitroPiperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4 — in vitro (human microsomes, Caco-2)View study →}. In 12 healthy volunteers, 20 mg of piperine a day for 10 days raised blood levels of the anti-epileptic carbamazepine by about half, by slowing its breakdown through CYP3A4 ^{34Reference 34Bedada et al. · 2017Clinical trialEffect of piperine on the metabolism and pharmacokinetics of carbamazepine in healthy volunteers — clinical studyView study →}. A single 20 mg dose raised steady-state phenytoin levels in people with epilepsy ^{35Reference 35Pattanaik et al. · 2006Clinical trialEffect of piperine on the steady-state pharmacokinetics of phenytoin in patients with epilepsy — clinical studyView study →}. In a small crossover study in healthy volunteers, 20 mg of piperine a day for a week raised blood levels of propranolol and theophylline ^{33Reference 33Bano et al. · 1991Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers — crossover studyView study →}. Short courses of isolated piperine have raised levels of several other drugs ^{6Reference 6Ziegenhagen et al. · 2021ReviewSafety aspects of the use of isolated piperine ingested as a bolus — reviewView study →}. Anyone taking a medicine with a narrow safety margin should check with their prescriber before taking a piperine supplement.

Culinary pepper. Animal studies support the safety of black pepper and piperine as food, and piperine was not genotoxic ^{7Reference 7Srinivasan · 2007ReviewBlack pepper and its pungent principle-piperine: a review of diverse physiological effects — reviewView study →}.

Isolated piperine. At higher daily doses than those used in human studies, isolated piperine disturbed sperm production and caused maternal reproductive and embryotoxic effects in animals. Human studies have rarely reported adverse effects, but few were designed to look for them ^{6Reference 6Ziegenhagen et al. · 2021ReviewSafety aspects of the use of isolated piperine ingested as a bolus — reviewView study →}.