White pepper

White pepper/Drug Interactions:

  • AnalgesicsAnalgesics: In animal study, piperine had analgesic effects (72). In in vitro study using whole-cell patch-clamp electrophysiology, piperine had similar agonist effects on the human vanilloid receptor TRPV1 as capsaicin (73). However, piperine could induce greater receptor desensitization and exhibit a greater efficacy than capsaicin.
  • AntiandrogensAntiandrogens: In an animal study, leaf extracts from Piper nigrum showed in vivo antiandrogenic activity.
  • AntibioticsAntibiotics: In vitro, white pepper (0.80% wt/vol) had antibacterial effects against Lactobacillus curvatus (74). Based on in vitro study using 12 different genera of bacterial populations isolated from the oral cavity of 200 individuals, Piper nigrum may have antibiotic activity (75). In animal study, piperine increased Cmax, Tmax, and area under the curve of beta-lactam antibiotics, amoxicillin trihydrate, and cefotaxime sodium (76). In in vitro study, piperine had additive effects with ciprofloxacin, potentially due to inhibition of bacterial efflux pumps (77). In animal study, Trikatu (an Ayurvedic prescription containing dried fruits of Piper nigrum and other spices) increased the area under the curve and volume of distribution of pefloxacin (78).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In vitro, piperine inhibited platelet aggregation (5).
  • Antidepressant agentsAntidepressant agents: In animal study, piperine had antidepressant effects, with reduced duration of immobility in the forced swimming test and the tail suspension test (79; 80). In animal study, piperine protected against chronic unpredictable mild stress (81; 82). Suppression of monoamine oxidase activity has also been implicated in the antidepressant effects of piperine (83; 84).
  • Antidiabetic agentsAntidiabetic agents: Based on animal study, piperine, a constituent of white pepper beneficially improved the plasma levels of insulin (12) and lowered the serum levels of glucose (15). Also, an aqueous extract of Piper nigrum seeds resulted in a lowering of blood sugar (14).
  • Antifungal agentsAntifungal agents: Based on secondary sources and in vitro study, constituents and oils of Piper nigrum may have antifungal effects (85).
  • AntihistaminesAntihistamines: In vitro, a polyherbal formulation (Aller-7/NR-A2) containing extracts from seven medicinal plants, including Piper nigrum, inhibited rat mesenteric mast cell degranulation, activity of lipoxygenase and hyaluronidase, and histaminic activity, and had an antispasmodic effect on contractions of guinea pig tracheal chain (86). It is unclear what the effects of Piper nigrum alone were.
  • AntihypertensivesAntihypertensives: In animal study, intravenous piperine had hypotensive effects (13).
  • Anti-inflammatory agentsAnti-inflammatory agents: Based on animal study, the benzene, chloroform, and ethanol extracts of leaf galls of Piper nigrum resulted in anti-inflammatory activity for carrageenan-induced acute inflammation in albino rats (87). Based on animal study, oral administration of a methanolic extract of Piper nigrum leaf resulted in inhibition in an immediate-phase and late-phase cutaneous swelling, potentially due to inhibition of histamine release (88). Based on animal study, piperine had anti-inflammatory effects in various inflammatory models (89; 90; 91). Based on animal study, a polyherbal formulation (Aller-7/NR-A2) containing extracts from seven medicinal plants, including Piper nigrum, demonstrated 31.3% inhibition against carrageenan-induced acute inflammation, while ibuprofen (50mg/kg orally) exerted 68.1% inhibition (92). It is unclear what the effects of Piper nigrum alone were. Based on animal study, the ED50 was lower in piperine-treated animals vs. animal treated with nimesulide alone, with superior anti-inflammatory effects (93). In animal study, Trikatu (an Ayurvedic prescription containing dried fruits of Piper nigrum and other spices) reduced the bioavailability of diclofenac sodium (94).
  • AntilipemicsAntilipemics: In animals, piperine reduced plasma lipids and lipoproteins levels, increased levels of HDL cholesterol, and improved levels of apo A-1 and apo B (12; 14).
  • AntineoplasticsAntineoplastics: In animal study, coumaperine, a constituent of white pepper, inhibited cancer cell proliferation and had protective effects against hepatocarcinogenesis (95). In vitro, piperine protected cells from cisplatin-induced apoptosis (96). In animal study, piperine increased tumor growth inhibition and reduced leukemia in 5-fluorouracil-treated animals (97).
  • Antiparasitic agentsAntiparasitic agents: In vitro, piperine had antiparasitic effects against Trypanosoma cruzi, which involved ultrastructural alterations (98; 99). In animal study, piperine had antiparasitic effects against Leishmania species (100; 101; 102). In vitro, Piper nigrum exhibited strong antinematodal activity against Bursaphelenchus xylophilus (103). In animal study, piperine demonstrated antiamebic activity for cecal amebiasis (104).
  • Antiseizure drugsAntiseizure drugs: In animal study, injected piperine blocked convulsions (105; 106) induced by intracerebroventricular injection of threshold doses of kainate, but had no or slight effects on convulsions induced by L-glutamate, N-methyl-D-aspartate, or guanidinosuccinate (105).
  • BenzodiazepinesBenzodiazepines: In vitro, piperine showed affinity for the benzodiazepine site on the GABA(A) (gamma-amino butyric acid) receptor (107).
  • CarbamazepineCarbamazepine: In epileptic patients, piperine significantly increased the mean plasma concentrations of carbamazepine, as well as area under the curve, Cmax, and Tmax (108).
  • Cardiac glycosidesCardiac glycosides: Based on in vitro study, piperine may inhibit digoxin transport in intestinal cells (109).
  • Cardiovascular drugsCardiovascular drugs: In vitro, piperine exerted cardiac myocyte protective effects (110). In animal study, piperine exerted positive chronotropic and inotropic effects in the isolated spontaneously beating right atria and electrically driven left atria; the calcitonin gene-related peptide was involved (111; 112).
  • Cholinergic agonistsCholinergic agonists: Based on in vitro study, extracts of Piper nigrum L. seeds may inhibit acetylcholinesterase (113).
  • CNS depressantsCNS depressants: Based on animal study, piperine potentiated pentobarbitone sleeping time and blood and brain levels of the drug (16). There was no effect on barbital sodium.
  • CyclosporineCyclosporine: Based on in vitro study, piperine may inhibit cyclosporine transport in intestinal cells (109).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: In animal and in vitro study, extracts of and constituents isolated from Piper nigrum, including piperine and dipiperamides D and E, potently inhibited some CYP450 metabolic pathways, including CYP2D6 (114; 115; 116), CYP3A4 (109; 117; 116; 118), CYP2B1 (119; 120), CYP1A1 (121), CYP2E1 (122), arylhydrocarbon hydroxylase, and 7-ethoxycourmarin deethylase (123; 124). P4502B and 1A expression were enhanced in rats (122). This has been also discussed in a review (125). Based on secondary sources, white pepper may decrease the rate of drug metabolism in the liver of certain drugs including lovastatin (Mevacor?), ketoconazole (NizoralTM), itraconazole (Sporanox?), fexofenadine (Allegra?), triazolam (HalcionTM), and others.
  • Diclofenac sodiumDiclofenac sodium: In animal study, Trikatu (an Ayurvedic prescription containing dried fruits of Piper nigrum and other spices) reduced the bioavailability of diclofenac sodium (94).
  • Fertility agentsFertility agents: In animal study, piperine had various negative effects on fertility in males, including alterations in enzyme levels, changes in lipid peroxidation, decreases in weight of testes and other sex organs, and damage to developing sperm (67; 68; 69). In females, negative effects of piperine included decreased mating performance and fertility (70). In superovulated female hamsters intragastrically treated with piperine, the percent fertilization following artificial insemination was increased (126).
  • Gastrointestinal agentsGastrointestinal agents: Based on in vitro study, a water-based extract of white pepper did not significantly inhibit activity of rat jejunal Na(+)-K(+)-ATPase (127). An alteration in the activity of Na(+)-K(+)-ATPase may cause important physiological changes in cell volume, intestinal processes, and kidney function.
  • Hepatotoxic agentsHepatotoxic agents: In animal study, piperine potentiated carbon tetrachloride-induced hepatotoxicity, potentially by increasing the activity of NADPH-cytochrome c reductase (6).
  • Hormonal agentsHormonal agents: In animals fed a high-fat diet resulting in negative effects on plasma lipids and hormone levels, piperine beneficially improved the plasma levels of testosterone (12). In vitro, the aqueous ethanolic Piper nigrum leaf extract resulted in inhibition of testosterone 5-alpha-reductase, and in animal study this extract had antiandrogenic activity, as observed using a hair growth assay in testosterone-sensitive male mice (128).
  • ImmunosuppressantsImmunosuppressants: In animal and in vitro study, piperine improved or returned to normal various immunological endpoints, such as cell viability, oxidative stress, apoptotic markers, cell proliferative response, T and B cell phenotype changes, and cytokine release, following treatment with the immunotoxicant cadmium (7; 8; 9; 10). In vitro piperine inhibited adhesion of neutrophils to endothelial monolayer; this is potentially due to its ability to block tumor necrosis factor-alpha (TNF-alpha)-induced expression of cell adhesion molecules such as ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), and E-selectin (11).
  • InotropesInotropes: In animal study, piperine exerted positive chronotropic and inotropic effects in the isolated spontaneously beating right atria and electrically driven left atria; the calcitonin gene-related peptide was involved (111; 112).
  • LithiumLithium: Based on secondary sources, white pepper might reduce the elimination of lithium from the body, which could increase drug levels and side effects from this medication.
  • NevirapineNevirapine: In human study, piperine enhanced the bioavailability of nevirapine (129).
  • OpioidsOpioids: Based on animal study, piperine may affect the intensity of morphine dependency (130).
  • P-glycoprotein regulated agentsP-glycoprotein regulated agents: In animal study, piperine may alter p-glycoprotein levels (131) and activity (132). In vitro, piperine had p-glycoprotein inhibitory (133; 131; 109) or biphasic activity (stimulation at low and inhibitory at high concentrations) (134). Based on secondary sources, white pepper increased the absorption of certain medications and increased their side effects. These medications include amprenavir, cimetidine, cisapride (PropulsidTM), corticosteroids, cyclosporine, digoxin, diltiazem, erythromycin, etoposide, fexofenadine (Allegra?), indinavir, itraconazole, ketoconazole, loperamide (Imodium?), nelfinavir, paclitaxel, quinidine, ranitidine, saquinavir, verapamil, vinblastine, vincristine, vindesine, and others.
  • Phenytoin (DilantinTM)Phenytoin (DilantinTM): Based on animal and clinical trials, piperine from Piper nigrum may enhance the bioavailability of phenytoin significantly, possibly by increasing its absorption (135; 136; 137; 138). Based on secondary sources, white pepper might increase positive and negative effects of phenytoin.
  • Propranolol (InderalTM)Propranolol (InderalTM): Based on a study in healthy volunteers, piperine may increase the bioavailability of propranolol (136; 139).
  • Respiratory agentsRespiratory agents: In animal study, piperine inhibits eosinophil infiltration and airway hyperresponsiveness; T cell activity suppression and inhibition of the production of interleukins-4 and -5 may play a role in this process (140). In human study, stimulation of the mucosa of the upper airway with white pepper powder caused dilation of the trachea and bronchi accompanied by a decrease in airway resistance in laryngectomized patients (3).
  • RifampinRifampin: Based on a study in patients with pulmonary tuberculosis, piperine may increase plasma concentrations of rifamipicin (rifampin) (136; 141). In animal study, Trikatu (an Ayurvedic prescription containing dried fruits of Piper nigrum and other spices) reduced the Cmax and plasma levels of rifampin (142).
  • StimulantsStimulants: In human study, inhalation of pepper oil increased plasma adrenaline (143).
  • TheophyllineTheophylline: Based on a study in healthy volunteers, piperine may increase the bioavailability of theophylline (136; 139).
  • Thyroid hormonesThyroid hormones: In animals fed a high-fat diet, piperine improved levels of T3, T4, and TSH (12; 15).
  • UDP substratesUDP substrates: In vitro, piperine slightly downregulated gene expression of UDP glucose dehydrogenase (144) and inhibited UDP-glucose dehydrogenase and glucuronidation activities in liver and intestine (145; 146), suggesting a role in the elimination of various drugs.

    • White pepper/Herb/Supplement Interactions:

  • AnalgesicsAnalgesics: In animal study, piperine had analgesic effects (72). In in vitro study using whole-cell patch-clamp electrophysiology, piperine had similar agonist effects on the human vanilloid receptor TRPV1 as capsaicin (73). However, piperine could induce greater receptor desensitization and exhibit a greater efficacy than capsaicin.
  • AntiandrogensAntiandrogens: In an animal study, leaf extracts from Piper nigrum showed in vivo antiandrogenic activity.
  • AntibacterialsAntibacterials: In sausages, white pepper (0.80% wt/vol) had antibacterial effects (74). Based on in vitro study using 12 different genera of bacterial populations isolated from the oral cavity of 200 individuals, Piper nigrum may have antibiotic activity (75). In animal study, piperine increased Cmax, Tmax, and area under the curve of beta-lactam antibiotics, amoxicillin trihydrate, and cefotaxime sodium (76). In vitro, piperine had additive effects with ciprofloxacin, potentially due to inhibition of bacterial efflux pumps (77). In animal study, Trikatu (an Ayurvedic prescription containing dried fruits of Piper nigrum and other spices) increased the area under the curve and volume of distribution of pefloxacin (78).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In vitro, piperine inhibited platelet aggregation (5).
  • Antidepressant agentsAntidepressant agents: In animal study, piperine had antidepressant effects, with reduced duration of immobility in the forced swimming test and the tail suspension test (79; 80). In animal study, piperine protected against chronic unpredictable mild stress (81; 82). Suppression of monoamine oxidase activity has also been implicated in the antidepressant effects of piperine (83; 84).
  • AntifungalsAntifungals: Based on secondary sources and in vitro study, constituents and oils of Piper nigrum may have antifungal effects (85).
  • AntihistaminesAntihistamines: In vitro, a polyherbal formulation (Aller-7/NR-A2) containing extracts from seven medicinal plants, including Piper nigrum, inhibited rat mesenteric mast cell degranulation, activity of lipoxygenase and hyaluronidase, and histaminic activity, and had an antispasmodic effect on contractions of guinea pig tracheal chain (86). It is unclear what the effects of Piper nigrum alone were.
  • Anti-inflammatory herbsAnti-inflammatory herbs: Based on animal study, the benzene, chloroform, and ethanol extracts of leaf galls of Piper nigrum resulted in anti-inflammatory activity for carrageenan-induced acute inflammation in albino rats (87). Based on animal study, oral administration of a methanolic extract of Piper nigrum leaf resulted in inhibition in an immediate-phase and late-phase cutaneous swelling, potentially due to inhibition of histamine release (88). Based on animal study, piperine had anti-inflammatory effects in various inflammatory models (89; 90; 91). Based on animal study, a polyherbal formulation (Aller-7/NR-A2) containing extracts from seven medicinal plants including Piper nigrum demonstrated 31.3% inhibition against carrageenan-induced acute inflammation, while ibuprofen (50mg/kg orally) exerted 68.1% inhibition (92). It is unclear what the effects of Piper nigrum alone were. Based on animal study, the ED50 was lower in piperine-treated animals vs. animals treated with nimesulide alone, with superior anti-inflammatory effects (93). In animal study, Trikatu (an Ayurvedic prescription containing dried fruits of Piper nigrum and other spices) reduced the bioavailability of diclofenac sodium (94).
  • AntilipemicsAntilipemics: In animals, piperine reduced plasma lipids and lipoproteins levels, increased levels of HDL cholesterol, and improved levels of apo A-1 and apo B (12; 14).
  • AntineoplasticsAntineoplastics: In animal study, coumaperine, a constituent of white pepper, inhibited cancer cell proliferation and had protective effects against hepatocarcinogenesis (95). In vitro, piperine protected cells from cisplatin-induced apoptosis (96). In animal study, piperine increased tumor growth inhibition and reduced leukemia in 5-fluorouracil-treated animals (97).
  • AntioxidantsAntioxidants: In animal study, the antioxidant coumaperine, a component of white pepper, provided protection against initiation of hepatocarcinogenesis, through inhibition of cell proliferation (95). In animal study, Piper nigrum had antioxidant potential against the free radical 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS); in combination with other spices (in Amrita Bindu) it also offered antioxidant potential (147). In animal study, piperine protected erythrocytes from oxidative stress and reduced oxidative stress associated with a high-fat diet (reduced thiobarbituric acid reactive substances (TBARS), glutathione, and conjugated dienes, and maintained superoxide dismutase, catalase, glutathione peroxidase, and glutathione S transferase) (148; 149).
  • AntiparasiticsAntiparasitics: In vitro, piperine had antiparasitic effects against Trypanosoma cruzi, which involved ultrastructural alterations (98; 99). In animal study, piperine had antiparasitic effects against Leishmania species (100; 101; 102). In vitro, Piper nigrum exhibited strong antinematodal activity against Bursaphelenchus xylophilus (103). In animal study, piperine demonstrated antiamebic activity for cecal amebiasis (104).
  • Antiseizure herbs and supplementsAntiseizure herbs and supplements: In animal study, injected piperine blocked convulsions (105; 106) induced by intracerebroventricular injection of threshold doses of kainate, but had no or slight effects on convulsions induced by L-glutamate, N-methyl-D-aspartate, or guanidinosuccinate (105).
  • CapsaicinCapsaicin: In human study, piperine applied to the tongue induced stimulus recovery under conditions of cross-sensitization with capsaicin (150; 151).
  • Cardiac glycosidesCardiac glycosides: Based on in vitro study, piperine may inhibit digoxin transport in intestinal cells (109).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: In vitro, piperine exerted cardiac myocyte protective effects (110). In animal study, piperine exerted positive chronotropic and inotropic effects in the isolated spontaneously beating right atria and electrically driven left atria; the calcitonin gene-related peptide was involved (111; 112).
  • Cholinergic herbsCholinergic herbs: Based on in vitro study, extracts of Piper nigrum L. seeds may inhibit acetylcholinesterase (113).
  • CurcuminCurcumin: In human study, a combination of piperine and curcumin resulted in a reduction in erythrocyte malondialdehyde levels in patients with tropical pancreatitis (152). Piperine acted as a bioavailability enhancer for curcumin, but bioavailability was not as good as that seen with curcumin encapsulated in nanoparticles (153). Addition of piperine to curcumin for efficacy study in animal models suggested piperine increased its absorption and efficacy in some (154; 155; 156) but not all (157) studies. According to a review, piperine might increase curcumin bioavailability by interfering with glucuronidation (158).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: In in vitro and animal study, extracts of and constituents isolated from Piper nigrum, including piperine and dipiperamides D and E, potently inhibited some CYP450 metabolic pathways, including CYP2D6 (114; 115; 116), CYP3A4 (109; 117; 116; 118), CYP2B1 (119; 120), CYP1A1 (121), CYP2E1 (122), arylhydrocarbon hydroxylase, and 7-ethoxycourmarin deethylase (123; 124). P4502B and 1A expression were enhanced in rats (122). This has been also discussed in a review (125). Based on secondary sources, white pepper may decrease the rate of drug metabolism in the liver of certain drugs including lovastatin (Mevacor?), ketoconazole (NizoralTM), itraconazole (Sporanox?), fexofenadine (Allegra?), triazolam (HalcionTM), and others.
  • Eclipta alba (false daisy)Eclipta alba (false daisy): In animal study, the combination of methanolic extracts of Piper nigrum and Eclipta alba increased activity of Eclipta alba, suggesting improved bioactivity in the presence of Piper nigrum (159).
  • (-)-Epigallocatechin-3-gallate (EGCG)(-)-Epigallocatechin-3-gallate (EGCG): Based on study in mice, piperine may enhance the bioavailability of EGCG, a polyphenol constituent from green tea (Camellia sinensis) (160).
  • Fertility agentsFertility agents: In animal study, piperine had various negative effects on fertility in males, including alterations in enzyme levels, changes in lipid peroxidation, decreases in weight of testes and other sex organs, and damage to developing sperm (67; 68; 69). In females, negative effects of piperine included decreased mating performance and fertility (70). In superovulated female hamsters intragastrically treated with piperine, the percent fertilization following artificial insemination was increased (126).
  • Ferulic acidFerulic acid: A combination of Piper nigrum and Angelica sinensis increased the relative bioavailability of ferulic acid (161).
  • Gallic acidGallic acid: In animal study, a combination of piperine and gallic acid had additive protective effects on beryllium-induced biochemical alterations and oxidative stress involved in hepatotoxicity (162).
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: Based on in vitro study, a water-based extract of white pepper did not significantly inhibit activity of rat jejunal Na(+)-K(+)-ATPase (127). An alteration in the activity of Na(+)-K(+)-ATPase may cause important physiological changes in cell volume, intestinal processes, and kidney function.
  • Green tea (Camellia sinensis)Green tea (Camellia sinensis): Based on study in mice, piperine may enhance the bioavailability of EGCG, a polyphenol constituent from green tea (Camellia sinensis) (160).
  • Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: In animal study, piperine potentiated carbon tetrachloride-induced hepatotoxicity, potentially by increasing the activity of NADPH-cytochrome c reductase (6).
  • Hormonal herbs and supplementsHormonal herbs and supplements: In animals fed a high-fat diet resulting in negative effects on plasma lipids and hormone levels, piperine beneficially improved the plasma levels of testosterone (12). In vitro, the aqueous ethanolic Piper nigrum leaf extract resulted in inhibition of testosterone 5-alpha-reductase, and in animal study this extract had antiandrogenic activity, as observed using a hair growth assay in testosterone-sensitive male mice (128).
  • HypoglycemicsHypoglycemics: Based on animal study, piperine, a constituent of white pepper beneficially improved the plasma levels of insulin (12) and lowered the serum levels of glucose (15). Also, an aqueous extract of Piper nigrum seeds resulted in a lowering of blood sugar (14).
  • HypotensivesHypotensives: In animal study, intravenous piperine had hypotensive effects (13).
  • ImmunosuppressantsImmunosuppressants: In animal and in vitro study, piperine improved or returned to normal various immunological endpoints, such as cell viability, oxidative stress, apoptotic markers, cell proliferative response, T and B cell phenotype changes, and cytokine release, following treatment with the immunotoxicant cadmium (7; 8; 9; 10). In vitro piperine inhibited adhesion of neutrophils to endothelial monolayer; this was potentially due to its ability to block tumor necrosis factor-alpha (TNF-alpha)-induced expression of cell adhesion molecules such as ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), and E-selectin (11).
  • InotropesInotropes: In animal study, piperine exerted positive chronotropic and inotropic effects in the isolated spontaneously beating right atria and electrically driven left atria; the calcitonin gene-related peptide was involved (111; 112).
  • P-glycoprotein-regulated agentsP-glycoprotein-regulated agents: In animal study, piperine may alter p-glycoprotein levels (131) and activity (132). In vitro, piperine had p-glycoprotein inhibitory (133; 131; 109) or biphasic activity (stimulation at low and inhibitory at high concentrations) (134). Based on secondary sources, white pepper increased the absorption of certain medications and increased their side effects. These medications include amprenavir, cimetidine, cisapride (PropulsidTM), corticosteroids, cyclosporine, digoxin, diltiazem, erythromycin, etoposide, fexofenadine (Allegra?), indinavir, itraconazole, ketoconazole, loperamide (Imodium?), nelfinavir, paclitaxel, quinidine, ranitidine, saquinavir, verapamil, vinblastine, vincristine, vindesine, and others.
  • Respiratory herbs and supplementsRespiratory herbs and supplements: In animal study, piperine inhibited eosinophil infiltration and airway hyperresponsiveness; T cell activity suppression and inhibition of the production of interleukins-4 and -5 may play a role in this process (140). In human study, stimulation of the mucosa of the upper airway with white pepper powder caused dilation of the trachea and bronchi accompanied by a decrease in airway resistance in laryngectomized patients (3).
  • RhodiolaRhodiola: In animal study, the combination of piperine and rhodiola extract reduced the activity of the rhodiola extract (163).
  • SedativesSedatives: Based on animal study, piperine potentiated pentobarbitone sleeping time and blood and brain levels of the drug (16). There was no effect on barbital sodium.
  • StimulantsStimulants: In human study, inhalation of pepper oil increased plasma adrenaline (143).
  • Thyroid agentsThyroid agents: In animals fed a high-fat diet, piperine improved levels of T3, T4, and TSH (12; 15).
  • UDP substratesUDP substrates: In vitro, piperine slightly downregulated gene expression of UDP (uridine diphosphate) glucose dehydrogenase (144) and inhibited UDP-glucose dehydrogenase and glucuronidation activities in liver and intestine (145; 146), suggesting a role in the elimination of various drugs.
  • ValerianValerian: In vitro, piperine showed affinity for the benzodiazepine site on the GABA(A) (gamma-amino butyric acid) receptor (107).

    • White pepper/Food Interactions:

  • ProteinProtein: In animal study, protein digestibility and biological value of the protein were increased in combination with a mixture of spices including Piper nigrum (164; 165).

    • White pepper/Lab Interactions:

  • AdrenalineAdrenaline: In human study, inhalation of pepper oil increased plasma adrenaline (143).
  • Blood glucoseBlood glucose: In animal study, piperine lowered serum glucose levels (15).
  • Blood pressureBlood pressure: Based on animal study, piperine may reduce blood pressure (13).
  • Coagulation panelCoagulation panel: Based on in vitro reports, piperine inhibited platelet aggregation (5).
  • Drug assaysDrug assays: Based on in vitro study, constituents isolated from Piper nigrum, including piperine and dipiperamides D and E, may potently inhibit some CYP450 metabolic pathways, including CYP2D6 (114) and CYP3A4 (109; 117). In animal study, piperine may alter p-glycoprotein levels (131) and activity (132). In vitro, piperine had p-glycoprotein inhibitory (133; 131; 109) or biphasic activity (stimulation at low and inhibitory at high concentrations) (134).
  • Gamma-glutamyl transpeptidase testGamma-glutamyl transpeptidase test: In animal study of metastases, piperine reduced serum activity of gamma-glutamyl transpeptidase activity (166).
  • Immune panelImmune panel: In animal and in vitro study, piperine improved or returned to normal, various immunological endpoints such as cell viability, oxidative stress, apoptotic markers, cell proliferative response, T and B cell phenotype changes, and cytokine release, following treatment with the immunotoxicant cadmium (7; 8; 9; 10). Based on animal study, piperine may result in a reduction of tumor necrosis factor-alpha (TNF-alpha) (167). In vitro piperine inhibited adhesion of neutrophils to endothelial monolayer; this was potentially due to its ability to block TNF-alpha-induced expression of cell adhesion molecules such as ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), and E-selectin (11).
  • Insulin levelsInsulin levels: In animals fed a high-fat diet resulting in negative effects on insulin, piperine beneficially improved the plasma levels of insulin (12).
  • Lipid profileLipid profile: In animals, piperine reduced plasma lipids and lipoproteins levels, increased levels of HDL cholesterol, and improved levels of apo A-1 and apo B (12; 14).
  • Nitric oxide levelsNitric oxide levels: Based on animal study, piperine may result in a reduction of nitrite (167).
  • Serotonin levelsSerotonin levels: In animal study, piperine stimulated serotonin synthesis (168).
  • Testosterone levelsTestosterone levels: In animals fed a high-fat diet resulting in negative effects on hormone levels, piperine beneficially improved the plasma levels of testosterone (12). In vitro, the aqueous ethanolic Piper nigrum leaf extract resulted in inhibition of testosterone 5-alpha-reductase, and in animal study this extract had antiandrogenic activity, as observed using a hair growth assay in testosterone sensitive male mice (128).
  • Thyroid function testsThyroid function tests: In animals fed a high-fat diet, piperine improved levels of T3, T4, and TSH (12).