Plant Part Used
Dried fruits
Active Constituents
Monoterpenes hydrocarbons (max. 80%): sabinene, beta-pinene, limonene, terpinene, alpha-pinene, myrcene, beta-carene, monoterpene derivative (borneol, carvone, carvacrol, 1,8-cineol, linalool); sesquiterpenes (beta-caryophyllene, humulene, beta-bisabolone & caryophyllene oxide, ketone); phenylether (eugenol, myristicine, safrole); odorants (linalool, alpha-phellandrene, limonene, myrcene and alpha-pinene); branched chain aldehydes (3-methylbutanal, methylpropanal), heterocyclic (2-isopropyl-3-methoxypyrazine, 2,3-diethyl-5-methylpyrazine); piperine:5-(2,4-dioxymethylene-phenyl)-hexa-2,4-dienoic acid (piperinic acid) with azinane (piperidine); piperine-analogs (5%): piperettine, piperyline, isobutylamine (piperlongumine); isobutylamide alkaloids: pellitorine, guineensine, pipercide, retrofractamide A; pipercyclobutanamides A and B. (1) , (2) , (3) , (4)
Introduction
Black pepper has long been used in Ayurvedic medicine for the treatment of various diseases. One such preparation known by the Sanskrit name is trikatu which consists of black pepper, long pepper, and ginger. It is thought that piperine is one of the major bioactive substances of these Ayurvedic remedies. (5) Black pepper has also been used in traditional Chinese medicine to treat seizure disorders. A derivative of piperine, antiepilepsirine, has also been used in China to treat seizure disorders. (6)
Black pepper is called the king of spices because it is one of the oldest spices with an aroma that is universally pleasant and appetizing. It is a stimulant of digestive juices as well as nerves and that is why it is an age old remedy for digestive disorders.
In India, pepper was used as a medicine for a variety of ailments from paralysis to toothaches. The east Africans believed that body odor produced after eating substantial amounts of pepper could repel mosquitoes. (7)
Dosage Info
Dosage Range
Piperine is available in supplement form and in combination products. A typical dose is 5 mg daily. Doses higher than 15 mg daily should be avoided. (8)
The Food and Drug Administration has included black pepper in the list of substances that are generally recognized as safe (GRAS) for their intended use.
Most Common Dosage
Piperine is available in supplement form and in combination products. A typical dose is 5 mg daily. Doses higher than 15 mg daily should be avoided. (9)
The Food and Drug Administration has included black pepper in the list of substances that are generally recognized as safe (GRAS) for their intended use.
Standardization
The herb is standardized to its piperine extract.
Toxicities & Precautions
Introduction
Use of this herb for irrigation therapy is contraindicated in the presence of edema resulting from reduced cardiac or renal activity.
Piperine is contraindicated for those who are hypersensitive to any component of a piperine-containing preparation.
Warnings: No irrigation therapy in cases of edema due to limited heart and kidney functions.
Peptic ulcer patients should avoid taking black pepper as it may cause discomfort and produce dyspepsia. (10)
Side Effects
The typical dose of piperine in nutritional formulas is 5 milligrams, and doses of 15 milligrams daily are rarely exceeded. No adverse reactions have been reported with these doses. Piperine, if exposed to the tongue, is tasteless at first but leaves a burning aftertaste. (11)
A study reported that piperine caused cytotoxicity to cerebellar granule neurons which could be alleviated by tocopherol suggesting a mechanism of lipid peroxidation, (12)
In a region of northern Iran, where esophageal cancer was higher among women than men, the main food during pregnancy contained strong black pepper and sharp crushed pomegranate seeds, which irritated the esophagus. (13)
A study in mice reported that topically applying and feeding mice 2mg of an extract from black pepper for 3 days a week for 3 months resulted in an increased number of tumor-bearing mice. This effect could be countered by 5 or 10 mg of vitamin A-palmitate given twice weekly for 3 months by feeding or topical application during and subsequent to application of pepper extract. On the other hand they found that feeding mice with the powder of black pepper in the diet (50g/3kg food) had no impact on carcinogenesis. (14)
First tumors appeared after two months of force feeding Egyptian toad Bufo regularis with an extract of black pepper at a dose of 2 mg, 3 times a week for 5 months. Tumors of the liver diagnosed as hepatocellular carcinomas, lymphosarcomas and fibrosarcomas, and those of the other organs, spleen, kidney, ovary, as metastases of the primary liver tumors. It is speculated that one or more constituents of black pepper may be responsible for the tumor induction in the organs. (15)
Pregnancy/ Breast Feeding
Pregnant women and nursing mothers should avoid piperine supplementation.
Age Limitations
Information is not available.
Pharmacology
Black pepper exhibited significant anti-inflammatory activity in carageenan-induced rat paw edema and in some other experimental models of inflammation. The mechanism of piperine putative anti-inflammatory activity in animal studies may be accounted for, in part, by its possible antioxidant activity. (16) In one animal study, piperine reduced liver lipid peroxidation, acid phosphatase, and edema induced by carageenan. (17)
The claim that piperine may aid in the digestion of food is based on experimental animal data showing that dietary piperine stimulated the secretion of digestive enzymes, pancreatic amylase, trypsin, chymotrypsin and lipase in rats. However, piperine appeared to have this activity when administered with other spice bioactives, such as capsaicin and curcumin, and not when administered by itself. (18)
Piperine inhibited many different cytochrome P450 isoforms, UDP-glucuronyltransferase, hepatic arylhydrocarbon hydroxylase and other enzymes involved in drug and xenobiotic metabolisms. (19)
There are studies demonstrating that piper nigrum can significantly increase the bioavailability of drugs and nutritional supplements. (20) It has increased the bioavailability of coenzyme Q10 (21) , curcumin (22) and beta-carotene. (23) It is speculated that piperine acted as a thermo-nutrient and increased the absorption of coenzyme Q10 from the gastrointestinal tract by producing a local thermogenic action. (24)
In humans given 2 grams of curcumin alone, the level of curcumin in serum was very low to undetectable one hour post-administration. The concomitant administration of 20 mg of piperine significantly increased absorption and bioavailability of curcumin. (25)
In a double-blind crossover study, 5 mg of piperine administered daily for 14-days resulted in a significant increase in serum beta-carotene levels. (26) The same dose of piperine produced similar results in another study involving coenzyme Q10. (27)
The claim that piperine may have anticonvulsant activity comes, in part, from China, where the substance was used to treat some forms of epilepsy. (28) In mice, piperine injected intraperitoneally was shown to significantly inhibit clonic convulsions induced by intracerebroventricular injection of kainite, but did not have or had only slight effects on seizure activity induced by L-glutamate, N-methyl-D-aspartate or guanidinosuccinate. (29)
Piperine was found to have antihepatotoxic potential by exerting a significant protection against tert-butyl hydroperoxide and carbon tetrachloride hepatotoxicity by reducing both in vitro and in vivo lipid peroxidation, enzymatic leakage of GPT and AP, and by preventing the depletion of GSH and total thiols in the intoxicated mice. (30)
On the negative side, piperine has shown some evidence of being mutagenic and potentially carcinogenic under some circumstances. It has reportedly given rise to mutagenic products on reaction with nitrites. This causes concern since nitrites and piperine may be consumed simultaneously. (31) Risk might increase with high-dose piperine supplementation.
The aqueous extract of black pepper was shown to possess antimutagenic properties. (32)
There are reports that cigarette cravings were reduced by inhalation of vapor from black pepper extract. In addition, negative effects and somatic symptoms of anxiety were alleviated in the pepper condition relative to the unflavored placebo. The intensity of sensations in the chest was also significantly higher for the pepper condition. (33)
Piyachaturawat (34) reported that the LD50 for a single i.v., i.p., s.c., i.g. and i.m. dose of piperine to male mice were 15, 43, 200, 330 & 400 mg/kg, with death by respiratory paralysis within 3-17 minutes. Hemorrhagic necrosis and edema were seen in the gastrointestinal and urinary tracts in subacute cases.
Piperine is a putative antispermatogenic agent. In a study utilizing albino rats, piperine was given at doses of 5 and 10mg per kg of body weight for 30 days. The 5-mg/kg dose resulted in partial degeneration of germ cell types. The 10-mg/kg dose level caused a significant reduction in the weights of the testes and accessory sex organs, severe damage to seminiferous tubules, decrease in seminiferous tubular and Leydig cell nuclear diameter, desquamation of spermatocytes spermatids, increase in serum gonadotropins and decrease in intratesticular testosterone. (35)
Reported Uses
There is preliminary evidence suggesting that piperine may aid in the digestion of food and may have anti-inflammatory (36) , anticonvulsant (37) , anticarcinogenic (38) , and inhibition of lung metastasis properties. (39)
It has long been recognized that volatile oil of piper nigrum has antibacterial activity. (40)
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2) Cultivation
3) Safety
References
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- Jirovetz L, Buchbauer G, Ngassoum MB, Geissler M. Aroma compound analysis of Piper nigrum and Piper guineense essential oils from Cameroon using solid-phase microextraction-gas chromatography, solid-phase microextraction-gas chromatography-mass spectrometry and olfactometry. J Chromatogr A. 2002;976:265-275.
- Fujiwara Y, Naithou K, Miyazaki T, et al. Two new alkaloids, pipercyclobutanamides A and B, from Piper nigrum. Tetrahedronn Letters. 2001;42:2497-2499.
- Park IK, Lee SG, Shin SC, Park JD, Ahn YJ. Larvicidal activity of isobutylamides identified in Piper nigrum fruits against three mosquito species. J Agric Food Chem. 2002;50(7):1866-1870.
- Johri RK, Zutshi U. An Ayurvedic formulation ‘Trikatu and its constituents. J Ethnopharmaco1. 1992;37(2):85-91.
- Pei YQ. A review of pharmacology and clinical use of piperine and its derivatives. Epilepsia. 1983;24:177-182.
- http://www.uta.edu/biology/arnott/abstracts/abs99a.htm
- http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/pip_0322.shtml.
- http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/pip_0322.shtml.
- Marotta RB, Floch MH. Diet and nutrition in ulcer disease. Med Clin North Am. 1991;75(4):967-79.
- http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/pip_0322.shtml.
- Unchern S, Saito H, Nishiyama N. Death of cerebellar granule neurons induced by piperine is distinct from that induced by low potassium medium. Neurochem Res. 1998;23(l):97-101.
- Ghadirian P, Ekoe JM, Thouez JP. Food habits and esophageal cancer: an overview. Cancer Detect Prev. 1992;16(3):163-8.
- Shwaireb MH, Wrba H, el-Mofty MM, Dutter A. Careinogenesis induced by black pepper (Piper nigrum) and modulated by vitamin A. Exp Pathol. 1990;40(4):233-8.
- el-Mofty MM, Soliman AA, Abdel-Gawad AF, Sakr SA, Shwaireb MH. Carcinogenicity testing of black pepper (Piper nigrum) using the Egyptian toad (Bufo regularis) as a quick biological test animal. Oncology. 1988;45(3):247-52.
- Mujumdar AM, Dhuley JN, Deshmukh VK, Raman PH, Naik SR. Anti-inflammatory activity of piperine. Jpn J Med Sci Biol. 1990;43(3):95-100.
- Dhuley JN, Raman PH, Mujumdar AM, Naik SR. Inhibition of lipid peroxidation by piperine during experimental inflammation in rats. Indian J Exp Biol. 1993;31:443-445.
- Platel K, Srinivasan K. Influence of digestive spices and their active principles on pancreatic digestive enzymes in albino rats. Nahrung. 2000;44:42-46.
- Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism. J Pharmacol Exp Ther. 1985;232:258-262.
- Majeed M, Badmaev V, Rajendran R. Use of piperine as a bioavailability enhancer. United States Patent No. 5,972,382. Oct. 26, 1999.
- Badmaev V, Majeed M, Prakash L. Piperine derived from black pepper increases the plasma levels of coenzyme Q10 following oral supplementation. J Nutr Biochem. 2000;11:109-113.
- Shoba G, Joy D, Joseph TM, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64:353-356.
- Badmaev V, Majeed M, Norkus EP. Piperine, an alkaloid derived from black pepper increases serum response of beta-carotene during 14-days of oral beta-carotene supplementation. Nutr Res. 1999;19:381-388.
- Badmaev V, Majeed M, Prakash L. Piperine derived from black pepper increases the plasma levels of coenzyme Q10 following oral supplementation. J Nutr Biochem. 2000;11:109-113.
- Shoba G, Joy D, Joseph TM, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64:353-356.
- Badmaev V, Majeed M, Norkus EP. Piperine, an alkaloid derived from black pepper increases serum response of beta-carotene during 14-days of oral beta-carotene supplementation. Nutr Res. 1999;19:381-388.
- Badmaev V, Majeed M, Prakash L. Piperine derived from black pepper increases the plasma levels of coenzyme Q10 following oral supplementation. J Nutr Biochem. 2000;11:109-113.
- Pei YQ. A review of pharmacology and clinical use of piperine and its derivatives. Epilepsia. 1983;24:177-182.
- D’Hooge R, Pei YQ, Raes A, Lebrun P, van Bogaert PP, de Deyn PP. Anticonvulsant activity of piperine on seizures induced by excitatory amino acid receptor agonists. Arzneimittelforschung. 1996;46(6):557-560.
- Koul IB, Kapil A. Evaluation of the liver protective potential of piperine, an active principle of black and long peppers. Planta Medica. 1993;59(5):413-417.
- Shenoy NP, Choughuley AS. Characterization of potentially mutagenic products from the nitrosation of piperine. Cancer Lett. 1992;64:235-239.
- El Hamss R, Idaomar M, Alonso-Moraga A, Munoz Serrano A. Antimutagenic properties of bell and black peppers. Food Chem Toxicol. 2003;41(1):41-47.
- Rose JE, Behin FM. Inhalation of vapor from black pepper extract reduces smoking withdrawal symptoms. Drug Alcohol Depend. 1994;34(3):225-229.
- Piyachaturawat P, Glinsukon T, Toskulkao C. Acute and subacute toxicity of piperine in mice, rats and hamsters. Toxicol Lett. 1983;16(3-4):351-9.
- Malini T, Manimaran RR, Arunakaran J, Aruldhas MM, Govindarajulu P. Effects of piperine on testis of albino rats. J Ethnopharmacol. 1999;64:219-225.
- Mujumdar AM, Dhuley JN, Deshmukh VK, Raman PH, Naik SR. Anti-inflammatory activity of piperine. Jpn J Med Sci Biol. 1990;43(3):95-100.
- D’Hooge R, Pei YQ, Raes A, Lebrun P, van Bogaert PP, de Deyn PP. Anticonvulsant activity of piperine on seizures induced by excitatory amino acid receptor agonists. Arzneimittelforschung. 1996;46(6):557-560.
- Wrba H, el-Mofty MM, Schwaireb MH, Dutter A. Carcinogenicity testing of some constituents of black pepper (Piper nigrum). Exp Toxicol Pathol. 1992;44(2):61-65.
- Pradeep CR, Kuttan G. Effect of piperine on the inhibition of lung metastasis induced B16F-10 melanoma cells in mice. Clinical and Experimental Metastasis. 2002;19(8):703-708.
- Dorman HJ, Deans SG. Antimicrobial agents from plants: antibacterial activity of plant volatile oils. J Appl Microbiol. 2000;88(2):308-316.
