Piperine use and health benefit by Ray Sahelian, M.D.
September 20 2019


Dried, ground pepper is one of the most common spices in European cuisine and its descendants, having been known and prized since antiquity for both its flavor and its use as a medicine. The spiciness of black pepper is due to the chemical piperine which has antioxidant, anti-inflammatory, anti-tumor potential.


Piperine and its derivatives exhibited a wide range of biological properties such as antitumor activity, antioxidant activity, antiinflammatory activity, antimycobacterial activity, and insecticidal activity.

Piperine and toxins
In mice, a significant suppression in the micronuclei formation induced by benzo(a)pyrene and cyclophosphamide was reduced following oral administration of piperine.

Benefit for oral absorption of other supplements and herbs
Q. I am a private practice veterinarian performing a research trial utilizing curcumin in horses for various inflammatory conditions. It is my understanding, that based on prior research, that curcumin bioavailability is compromised and in turn the absorption and therapeutic blood levels are low. I also understand that various research trials are demonstrating the concurrent use of piperine, which enhances the absorption and bioavailability. I am curious if your research supports this as well and if there is any further information that you might have to support this fact.
   A. I need to see results of several more studies before having a strong opinion on this topic. For the time being, my understanding is that piperine may help with curcumin absorption or bioavailability in humans if the dosage of the curcumin is low, but may not have an influence if it is high. Almost all studies with curcumin have not used any piperine, therefore I tend to think that curcumin works well by itself. Here is a summary of two human studies:

Neurotox Res. 2011. Protective effect of curcumin and its combination with piperine (bioavailability enhancer) against haloperidol-associated neurotoxicity: cellular and neurochemical evidence. The researchers state, "Co-administration of piperine significantly enhanced the effect of curcumin (25 mg/kg) but not of curcumin (50 mg/kg)." A dosage of 50 mg/k is equal to about 3.5 grams in a 70 kg human.


Planta Med. 1998. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. In humans after a dose of 2 grams curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug, the increase in bioavailability was 2000%.

Q. Is piperine necessary for absorption of chrysin?
   A. We have not come across any research that says piperine is necessary for this purpose.


Piperine for mood support
Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms.
Life Sci. 2007.
In this study, we investigated the antidepressant effect of piperine in mice exposed to chronic mild stress procedure. Repeated administration of piperine for 14 days at the doses of 2.5, 5 and 10 mg/kg reversed the stress -induced changes in sucrose consumption, plasma corticosterone level and open field activity. Furthermore, the decreased proliferation of hippocampal progenitor cells was ameliorated and the level of brain-derived neurotrophic factor in hippocampus of CMS stressed mice was up-regulated by piperine treatment in the same time course. In summary, up-regulation of the progenitor cell proliferation of hippocampus and cytoprotective activity might be mechanisms involved in the antidepressant like effect of piperine.


Q. I would like to ask if you are aware of any evidence of piperine's activity posing risks for bipolar depression. I take piperine at 30mg daily.
   A. I am not aware of any studies that have examined this issue.


Piperine as antioxidant
Efficacy of piperine, an alkaloidal constituent from Piper nigrum on erythrocyte antioxidant status in high fat diet and antithyroid drug induced hyperlipidemic rats.
Cell Biochem Funct. 2006.
The main aim of this study was to investigate the effect of piperine on erythrocyte antioxidant status in high fat diet (HFD) and antithyroid drug induced hyperlipidemic rats. Male Wistar rats were divided into eight groups. The first four groups were fed a control diet and in addition were given respectively 1% carboxymethyl cellulose (CMC); 10 mg/kg body weight carbimazole (CM); 10 mg CM + 40 mg/kg body weight piperine and 10 mg CM + 2 mg/kg body weight atorvastatin. A similar pattern was followed for the next four groups except that they were all fed HFD instead of the control diet. Erythrocyte osmotic fragility, total cholesterol, phospholipids, lipid peroxidation products, enzymic and non-enzymic antioxidant status were studied in all experimental groups. Significantly increased osmotic fragility, total cholesterol/phospholipid ratio, thiobarbituric acid reactive substances and lipid hydroperoxides were observed in the plasma and erythrocytes of HFD fed and CM treated rats compared to the control. Superoxide dismutase, catalase, glutathione peroxidase, vitamin E and reduced glutathione in erythrocytes and vitamin C in the plasma were also significantly lowered in HFD fed, antithyroid drug treated rats compared to control animals. Concurrent piperine supplementation along with HFD and antithyroid drug administration normalized erythrocyte osmotic fragility, reduced lipid peroxidation, and improved the enzymic and non-enzymic antioxidant status compared to those rats that did not receive piperine. Ppiperine supplementation markedly protects erythrocytes from oxidative stress by improving the antioxidant status in HFD fed antithyroid drug treated rats.


Piperine and blood pressure
It appears that piperine may lower blood pressure but could also constrict blood vessels. Different animals appear to have a different response to the effects of piperine. The influence of a piperine supplement on blood pressure in humans remains to be evaluated.

Blood pressure lowering and vasomodulator effects of piperine.
J Cardiovasc Pharmacol. 2008. Department of Pharmaceutical Sciences; Federal Urdu University of Arts, Science and Technology, Gulshan Campus Karachi, Pakistan.
This study was aimed to explore underlying mechanism(s) of cardiovascular effects of piperine. Intravenous administration of piperine caused a dose-dependent (1 to 10 mg/kg) decrease in mean arterial pressure in normotensive anesthetized rats; the next higher dose (30 mg/kg) did not cause any further change in mean arterial pressure. The fall in blood pressure was followed by small increase in MAP after each dose. In Langendorrf's rabbit heart preparation, piperine caused partial inhibition and verapamil caused complete inhibition of force and rate of ventricular contractions and coronary flow. In rabbit aortic rings, piperine inhibited high K+ precontractions and partially inhibited phenylephrine (PE), suggesting Ca2+ channel blockade. In rat aorta, piperine demonstrated endothelium-independent vasodilator effect and was more potent against high K+ precontractions than PE. Our data indicate that piperine possesses a blood pressure-lowering effect mediated possibly through calcium channel blockade, while consistent decrease in BP was restricted by associated vasoconstrictor effect. Additionally, species selectivity exists in the calcium channel blockade effect of piperine.


J Physiol Pharmacol. December 2013. The analgesic and anticonvulsant effects of piperine in mice. Findings indicate that piperine exhibits analgesic and anticonvulsant effects possibly mediated via opioid and GABA-ergic pathways respectively. Moreover, piperine being the main constituent of black pepper, may be contributing factor in the medicinal uses of black pepper in pain and epilepsy.

Piperine and drug Interactions
Piperine from black (Piper nigrum) and long (P. longum) peppers increased the AUC of phenytoin, propranolol and theophylline in healthy volunteers and plasma concentrations of rifamipicin (rifampin) in patients with pulmonary tuberculosis.


Piperine side effects, safety, toxicity
Not enough human studies have been done to determine the side effects of chronic supplementation with piperine. For the time being, it is a good idea to take 2 days off a week, and one full week off each month from the use of a piperine supplement. It is quite likely that small amounts could provide health benefits while larger amounts could be toxic or damaging to the liver or other organs.


Piperine Research

Studies on the chemical constituents from herb of Rhodobryum roseum
Zhongguo Zhong Yao Za Zhi. 2005.
To study the chemical constituents from herb of Rhodobryum roseum. The compounds were isolated by column chromatography, and identified by IR, NMR data. Eight compounds were isolated and identified. They are piperine, caffeic acid methyl ester, uracil glucoside, ursolic acid, 5alpha, 8alpha-epidioxy-methylcholesta-6, 22-dien-3beta-ol, 5alpha, 8alpha-epidioxy-methylcholesta-6,9, 22-trien-3beta-ol, beta-sitosterol and daucosterol.


Piperine: researchers discover new flavor in an ancient spice.
Trends Pharmacol Sci. 2005.
Studies with animals that are deficient in the vanilloid (capsaicin) receptor TRPV1 have confirmed the pivotal role that TRPV1 has in the development of post-inflammatory hyperalgesia, and enhanced TRPV1 expression has been described in various human disorders. Natural products have provided several lead structures for the development of vanilloid ligands. A recent study shows that piperine, the irritant principle in black pepper, is more efficient than capsaicin in the desensitization of human TRPV1, which suggests that this pharmacological aspect of vanilloids can be dissociated from its potency. This finding raises the intriguing possibility that piperine can be used as a chemical template for the design of improved TRPV1 agonists.


Immunomodulatory and antitumor activity of Piper longum and piperine.
J Ethnopharmacol. 2004.
Alcoholic extract of the fruits of the plant Piper longum and its component piperine was studied for their immunomodulatory and antitumor activity. Alcoholic extract of the fruits was 100% toxic at a concentration of 500 microg/ml to Dalton's lymphoma ascites (DLA) cells and 250 microg/ml to Ehrlich ascites carcinoma (EAC) cells. Piperine was found to be cytotoxic towards DLA and EAC cells at a concentration of 250 microg/ml. Alcoholic extract and piperine was also found to produce cytotoxicity towards L929 cells in culture at a concentration of 100 and 50 microg/ml, respectively. Administration of alcoholic extract of Piper longum (10 mg/dose/animal) as well as piperine (1.14 mg/dose/animal) could inhibit the solid tumor development in mice induced with DLA cells and increase the life span of mice bearing Ehrlich ascites carcinoma tumor to 37.3 and 58.8%, respectively. Administration of Piper longum extract and piperine increased the total WBC count to 142.8 and 138.9%, respectively, in Balb/c mice. The number of plaque forming cells also enhanced significantly by the administration of the extract (100.3%) and piperine (71.4%) on 5th day after immunization. Bone marrow cellularity and alpha-esterase positive cells were also increased by the administration of Piper longum extract and piperine.



Q. I heard of the benefits in guinea pig skin pigmentation with topical piperine. I'm a researcher in Italy really interested in new experiences for treating this disease, I would like to know if you have experience with piperine also in vitiligo?
   A. I have not studied the role of piperine in vitiligo.


Q. I've been looking into some natural remedies to reduce dark circles under the eyes. I came across a recipe for a topical paste that includes turmeric powder. After looking into this substance, I came across information stating that piperine can dramatically increase the absorption rate of turmeric. So I got the bright idea to add some of this to this recipe. The recipe is:

1 tsp. tomato juice
1/2 tsp. lemon juice
pinch of turmeric powder
pinch of gramflour

This will create a paste that you apply under your eyes for 10 minutes. So would adding a source of piperine, like say for example your Bioperine make this recipe more effective in your professional opinion? And above all else, would it be safe, because if not the rest is moot.
    A. The research done with piperine and absorption that I am familiar with has to do mostly with absorption from the stomach not the skin. I have no idea whether piperine applied topically would help or cause an allergic or toxic reaction to the skin or the eyes if it happens to go in the eye. This is not an area I have studied.


Source Naturals piperine, Bioperine 10 mg
Black Pepper fruit extract with 95 percent piperine

Buy piperine

Buy piperine, Bioperine - a standardized extract of piperine.


Supplement Facts
Serving Size: 1 Tablet
  Amount Per Serving %DV
Calcium 28 mg 3%
Black Pepper Fruit Extract (BioPerine) Yielding 95% Piperine 10 mg
†Daily Value not established.