[ScottL]

These are the posts on imminst made by AORsupport on bioperine:

When we saw the enhanced bioavailability conferred on curcumin by piperine, AOR was initially excited, as bioavailability of curcumin in humans is very low (and proportionately much lower than in rodents, in whom very promising research has been performed). Once we began digging into the research on this substance, however, we concluded that it would be irresponsible to systematically increase exposure to this phytochemical.

It's worth gaining some understanding of exactly why piperine enhances the bioavailability of some substances (and only some: there seems to be a widespread belief in the industry that piperine enhances absorption of all nutrients, such that you see piperine mixed in with almost any supplement you care to mention -- even basic multivitamins). While there are several mechanisms at work, the primary one is the inhibition of detoxification enzymes, including a highly nospecific effect on the Phase I (cytochrome P450) enzymes, and an impairment of glucuronidation (a Phase II conjugation process). Piperine is "a potent inhibitor of UDP-GDH [UDP-glucose dehydrogenase (UDP-GDH)]” and of "glucuronidation potentials of rat and guinea pig liver and intestine" [1]. It is "a nonspecific inhibitor of drug metabolism which shows little discrimination between different cytochrome P-450 forms. Oral administration of piperine in rats strongly inhibited the hepatic AHH [arylhydrocarbon hydroxylase] and UDP-glucuronyltransferase activities." [2] "Piperine caused a concentration-related decrease in UDP-glucuronic acid content and the rate of glucuronidation in the [intestinal] cells. ... Rate of glucuronidation ... was dependent on the endogeneous level of UDP-glucuronic acid. At 50 microM piperine, the rate of glucuronidation was reduced to about 50% of the basal rate. Piperine caused noncompetitive inhibition of hepatic microsomal UDP-glucuronyltransferase with Ki of 70 microM." [3]

Substances whose bioavailability is inhibited by being biotransformed by these enzymes will therefore have their bioavailability enhanced by piperine. This is the basis, in particular, for its enhancement of curcumin bioavailability. The problem with this is that these enzymes also protect us from a variety of toxic substances -- which is, after all, why we have them in the first place.

Thus, "piperine was found to promote DNA damage and cytotoxicity induced by benzo[a]pyrene (B[a]P [a carcinogenic compound formed as a result of incomplete combustion of organic materials, found in engine exhaust, coal-, oil-, and wood-burning stove emissions, poorly-tuned furnaces, cigarette smoke, industrial soot, charred foods, incinerators, coke ovens, and asphalt processing, and secondarily in contaminated drinking water] in cultured V-79 lung fibroblast cells ... due to mechanisms that decrease the activities of [the detoxification enzymes] GST [glutathione S-transferase] and UDP-GTase [uridine diphosphate glucuronyl transferase] and increase the formation of a B[a]P-DNA adduct.” [4] Likewise [3] finds that piperine inhibits the "Rate of glucuronidation of 3-hydroxybenzo (a) pyrene ... dependent on the endogeneous level of UDP-glucuronic acid. "

It also "enhances the bioavailability of aflatoxin B1 in rat tissues," although the net effect of this is unclear [5]; aflatoxin is a mycotoxin that often contaminates corn and peanuts that are not kept dry and refrigerated, and is still a major cause of hepatocelluar carcinoma in China and much of the developing world. While under control in OECD countries, it is certainly not absent from the food supply, and enhancing its bioavialability is prima facie a bad idea.

Independently of impaired detoxification, "Piperine ... also reacted with nitrite and produced compounds showing mutagenicity in bacteria without metabolic activation." [6]

It should be noted that in other models, piperine appears to be protective against aspects of the cancer process, but the state of research is not clear enough to allow anyone to perform a reliable risk-to-benefit analysis of piperine. Healthy life extensionists, in our judgement, should avoid it.

To your health!

AOR

1. Reen RK, Jamwal DS, Taneja SC, Koul JL, Dubey RK, Wiebel FJ, Singh J. Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine. Biochem Pharmacol. 1993 Jul 20;46(2):229-38.

2. 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 Jan;232(1):258-62.


3. Singh J, Dubey RK, Atal CK. Piperine-mediated inhibition of glucuronidation activity in isolated epithelial cells of the guinea-pig small intestine: evidence that piperine lowers the endogeneous UDP-glucuronic acid content. J Pharmacol Exp Ther. 1986 Feb;236(2):488-93.

4. Chu CY, Chang JP, Wang CJ. Modulatory effect of piperine on benzo[a]pyrene cytotoxicity and DNA adduct formation in V-79 lung fibroblast cells. Food Chem Toxicol. 1994 Apr;32(4):373-7.

5. Allameh A, Saxena M, Biswas G, Raj HG, Singh J, Srivastava N. Piperine, a plant alkaloid of the piper species, enhances the bioavailability of aflatoxin B1 in rat tissues. Cancer Lett. 1992 Jan 31;61(3):195-9.

6. Wakabayashi K, Nagao M, Sugimura T. Mutagens and carcinogens produced by the reaction of environmental aromatic compounds with nitrite. Cancer Surv. 1989;8(2):385-99.

That it enhances bioavailability of some (again, not all) substances is not disputed. The point, again, is that glucuronidation is a central detoxification process. Unless you have a totally toxin-free diet -- no overcooked foods, no pesticide residues in your meats and vegetables, no trace quantities of mycotoxins in your bread, etc -- and unless you have no sex steroids in your system, you rely on these processes to protect you against cancer on a continuous basis. Inhibiting them for a few hours every day to get better bioavailability out of your supplements is rather to mix up one's priorities.

To your health!

AOR

Thanks for digging it out Funk.

[comfortable_pants]

this is by no means my attempt to defend thermolife since they have bioperine in ecdysten, but i just like to play devil's advocate instead of the chicken running around with it's head cut off.
It seems like everything does something that causes cancer; the water i'm drinking will cause cancer (we have crappy tap water here), going outside and breathing air will cause cancer. The important question is "to what degree?" does bioperine lead to a high degree of carcinogens, or is it a minute amount? does a diet full of antioxidants help? Is using it for a few weeks to a few months safe? (these are legit questions, not rhetorical.)
I think this like sums it up well: "the state of research is not clear enough to allow anyone to perform a reliable risk-to-benefit analysis of piperine."

But it is good that we are aware that there is a possibility of adverse effects. thanks

[ScottL]

This is not a simple topic, and from your reply I'm not sure you fully understand.

The bottom line IMHO is that bioperine inhibits some of the body's detoxification enzymes. There are reasons above why this ain't a great idea.

Edit: BTW I certainly have nothing against thermolife and had a good impression in general based on Truthspeaker's posts.

[comfortable_pants]

This is not a simple topic, and from your reply I'm not sure you fully understand.

bioperine inhibits detox enzymes, creates carcinogens, and increases the bioavailability of aflotoxin b1. am i missing anything else?

[liorrh]

Not sure why its such big news to you. I've said, it and explained it, about a zillion times in this here forum. Maybe I should add "Support" to my handle.

[Section 8]

I've been telling people not to use this crap for almost four years.

[ScottL]

Not sure why its such big news to you. I've said, it and explained it, about a zillion times in this here forum. Maybe I should add "Support" to my handle.

Lior,

If that was towards me I've known about it for ages. I didn't remember to what degree the full reasoning was discussed, and someone had asked about it in the last few days. So when I saw the full discussion I thought it worth posting.

[liorrh]

cool, its better to know something twice than to not know it at all.

[trouble]

"whomever they hate, whatever they hate..._that_ thas value".

Oral supplementation of piperine leads to altered phase II enzymes and reduced DNA damage and DNA-protein cross links in Benzo(a)pyrene induced experimental lung carcinogenesis. Selvendiran K, Banu SM, Sakthisekaran D. Mol Cell Biochem. 2005 Jan;268(1-2):141-7.

In recent years, considerable emphasis has been focused on identifying new chemopreventive agents, which could be useful for the human population. Piperine is a pure, pungent alkaloid constituent of black and long peppers (piper nigrum and piper longum), which is a most common spice used throughout the world. In the present study, we examined the protective role of piperine during experimental lung carcinogenesis with reference to its effect on DNA damage and detoxification enzyme system. The activities of detoxifying enzymes such as glutathione transferase (GST), quinone reductase (QR) and UDP-glucuronosyl transferase (UDP-GT) were found to be decreased while the hydrogen peroxide level was increased in the lung cancer bearing animals.

---> Supplementation of piperine (50 mg/kg bwt) enhanced the detoxification enzymes and reduced DNA damage as determined by single cell electrophoresis.

---->Furthermore, the DNA-Protein cross links which was found to be high in lung cancer bearing animals was also modulated upon supplementation with piperine.

--->Our present results explain the understanding of unique association between anti-peroxidative effect of piperine and ultimately the capability of piperine to prevent cancer.

[trouble]

Chemopreventive effect of piperine on mitochondrial TCA cycle and phase-I and glutathione-metabolizing enzymes in benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice.

Selvendiran K, Thirunavukkarasu C, Singh JP, Padmavathi R, Sakthisekaran D. Mol Cell Biochem. 2005 Mar;271(1-2):101-6.

Piperine is a major component of black (Piper nigrum Linn) and long pepper (Piper longum Linn) used widely in various systems of traditional medicine. We have evaluated the effect of piperine on mitochondrial tricarboxylic acid cycle and phase I and glutathione-metabolizing enzymes in Benzo(a)pyrene induced experimental lung carcinogenesis in swiss albino mice. Lung cancer bearing mice showed a significant decrease in the activities of mitochondrial enzymes-isocitrate dehydrogenase (ICDH), -ketoglutarate dehydrogenase (KDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and significantly increased NADPH-Cytochorome reductase (NADPH-C reductase), cytochrome P450 (cyt-p450) and cytochrome b5(cyt-b5). The activities of glutathione-metabolizing enzymes glutathione peroxidase(GPx), glutathione reductase (GR) and glucose-6-phospho dehydrogenase(G6PDH) were significantly lowered in lung-cancer bearing mice when compared with control mice.

---> Piperine supplementation to tumour-induced animals significantly lowered the phase-I enzymes (NADPH-C reductase, cyt-p450 and cyt-b5)) and there was a rise in glutathione-metabolizing enzymes (GPx, GR and G6PDH), which indicated an antitumour and anti-cancer effect.

Comparison of normal control mice and mice administered piperine only as drug control showed no significant variations in enzyme activities.

---> Piprine administration to benzo(a)pyrene induced animals significantly increased the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.

[trouble]

In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Sharma P, Varma MV, Chawla HP, Panchagnula R. Farmaco. 2005 Nov-Dec;60(11-12):874-83.

The present investigation attempts to increase intestinal permeability and hence absorption of biopharmaceutic classification system (BCS) Class III (cefotaxime sodium (CX)) and Class IV (cyclosporin A (CSA)) drugs by employing certain absorption enhancers. Drugs were co-perfused with sodium caprate (SC, 0.25% w/v), piperine (P, 0.004% w/v) and sodium deoxycholate (SD, 1.0% w/v) separately in rat in situ single pass intestinal perfusion model. These additives increased intestinal permeability (P(app)) and absorption rate constant (K(a)) up to two and fourfold, respectively. SC exhibited substantial absorption enhancement of both CX and CSA, while SD and P enhanced absorption of CX and CSA, respectively. Co-administration of SC significantly enhanced peroral bioavailability of CX (from 29.4 +/- 1.7 to 69.6 +/- 3.2) and CSA (from 18.4 +/- 15.6 to 49.6 +/- 25.1) in rats, while P increased bioavailability of CSA (from 18.4 +/- 15.6 to 33.1 +/- 17.7). Transmission electron microscopy of intestinal mucosa revealed that SC and SD act on lipid and protein domains of absorptive membrane. P showed no effect on intestinal P(app) and oral bioavailability of CX but has a profound effect on CSA, a known P-glycoprotein (P-gp) substrate. These results indicated that P enhances intestinal absorption of CSA by modulating P-gp mediated efflux transport. Release of lactate dehydrogenase in situ from intestinal mucosa in the presence of absorption enhancer was taken as index of its local toxicity. All the absorption enhancers showed significantly less release of LDH compared to positive control, sodium dodecyl sulfate (60% w/v).

---->Overall, the data indicate that the features of these commonly used food ingredients or endogenous bile salts can effectively improve bioavailability of various BCS Class III and Class IV drugs.

[trouble]

Immunotoxicological effects of piperine in mice. Dogra RK, Khanna S, Shanker R. Toxicology. 2004 Mar 15;196(3):229-36

The immunotoxicological effects of piperine were investigated in Swiss male mice, gavaged at a dose of 1.12, 2.25 or 4.5 mg/kg body weight for five consecutive days. All the dose levels had no overt toxic effect and the liver gained weight normally. Treatment at highest dose, however, resulted in significant decrease in the weight of spleen, thymus and mesenteric lymph nodes, but not of peripheral lymph nodes. All the dose levels suppressed the cellular population of lymphoid organs, except for the spleen, where the doses of 1.12 and 2.25 caused an increase. Haematologically, doses of 2.25 and 4.5 mg/kg caused a significant reduction in total leucocyte counts and differential leucocyte counts showed an increase in the percentage of neutrophils. The higher doses of 2.25 and 4.5 mg/kg suppressed the mitogenic response of B-lymphocyte to lipopolysaccharide. The number of primary antibody (IgM) forming cells in the spleen and the level of primary antibody in serum, was decreased. The doses of 1.12 and 2.25 mg/kg suppressed the mitogenic response of T-lymphocytes to phytohaemagglutinin and the nitroblue tetrazolium (NBT) dye reducing activity of peritoneal exudate cells (PECs).

----> Since the lowest dose of 1.12 mg of piperine per kg body weight had no immunotoxic effect, it may be considered as immunologically safe "no observed adverse effect level (NOAEL)" dose.

[trouble]

Screening of the inhibitory effect of vegetable constituents on the aryl hydrocarbon receptor-mediated activity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCCD). Amakura Y, Tsutsumi T, Sasaki K, Yoshida T, Maitani T. Biol Pharm Bull. 2003 Dec;26(12):1754-60.

The aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear transcription factor that mediates responses to environmental contaminants such as dioxins, which have many adverse health effects. We performed a preliminary screening of the inhibitory effects of vegetable constituents on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of AhR using the AhR-based bioassay for dioxins, the Ah-Immunoassay. Ninety vegetable constituents including flavonoids, tannins, saponins, terpenes, etc., were assayed in vitro. Among them, flavones, flavonols, anthraquinones, piperine, coumestrol, brevifolincarboxylic acid, and resveratrol showed marked inhibitory effects on AhR-based bioassay activation by TCDD, and their effects were dose dependent.

--->Curcumin, carnosol, and capsaicin also inhibited the activation of AhR in this assay, although to a lesser degree. (SAME FUCKING MECHANISM)

--->These results suggest that several vegetable constituents might play a role in protection against dioxin toxicity.

[trouble]

Comparative anti-nociceptive, anti-inflammatory and toxicity profile of nimesulide vs nimesulide and piperine combination. Gupta SK, Bansal P, Bhardwaj RK, Velpandian T. Pharmacol Res. 2000 Jun;41(6):657-62.

Piperine is an inhibitor of various hepatic and other enzymes involved in the biotransformation of drugs. Preliminary pharmacokinetic studies conducted by us suggested the increased bioavailability of nimesulide co-administered with piperine. The present study was, thus, conducted to evaluate the antinociceptive, anti-inflammatory and toxicity profile of a new nimesulide-piperine combination administered orally as compared with nimesulide alone. Antinociceptive efficacy was tested using an acetic acid writhing test and tail flick latency test (TFL). The ED50 value of a nimesulide-piperine combination in writhing test was calculated to be significantly lower (1.5 mg kg(-1)) as compared to (11.2 mg kg(-1)) of nimesulide alone. The antinociceptive effect was lesser in the tail flick latency test as compared to what was observed in the writhing test indicating the peripheral action of the Non-Steriodal Anti-Inflammatory Drug (NSAID). In carrageenan-induced inflammatory tests, the nimesulide-piperine combination was found to be dose-to-dose superior than nimesulide alone. Acute toxicity studies on mice revealed a reduction in lethal dose (LD50) of the combination (980 mg kg(-1)) as compared to nimesulide (1500 mg kg(-1)) alone.

--->Results from the present study suggest a better therapeutic index for the nimesulide-piperine combination indicating that this combination would further reduce the frequency of adverse effects associated with nimesulide alone.

This novel use of piperine to reduce toxicity of certain oral pharmacological agents (in this case, anti-inflammatory and pain-relief action) is another unexpected benefit of this compound.

[trouble]

Piperine inhibits aflatoxin B1-induced cytotoxicity and genotoxicity in V79 Chinese hamster cells genetically engineered to express rat cytochrome P4502B1. Reen RK, Wiebel FJ, Singh J. J Ethnopharmacol. 1997 Nov;58(3):165-73

We have investigated the potential of piperine for inhibiting the activity of cytochrome P4502B1 and protecting against aflatoxin B1 (AFB1) in V79MZr2B1 (r2B1) cells, i.e. V79 Chinese hamster cells engineered for the expression of rat CYP4502B1. The cells were found to contain high activities of 7-methoxycoumarin demethylase (MOCD). Piperine inhibited MOCD in preparations of r2B1 cells with an IC50 of approximately 10 microM. The cells in culture dealkylated 7-methoxycoumarin (MOC) to 7-OH-coumarin linearly, at least for 12 h, where piperine produced concentration-dependent inhibition with IC50 < 30 microM. The time required for maximal inhibition was approximately 8 h with both 30 and 60 microM concentrations of piperine used. AFB1 at 0.1-20 microM caused a concentration dependent decrease in the amount of DNA and an increase in the formation of micronuclei (MN). The mycotoxin at 10 microM reduced DNA by approximately 30% and increased MN appearance by 20-fold against the background level of 7 MN per 500 nuclei. Piperine at 60 microM completely counteracted cytotoxicity and formation of MN by 10 microM AFB1 and reduced the toxic effects of 20 microM AFB1 by > 50%.

---> nThe results suggest that: (i) Piperine is a potent inhibitor of rat CYP4502B1 activity; (ii) AFB1 is activated by r2B1 cells to cytotoxic and genotoxic metabolites; and (iii) piperine counteracts CYP4502B1 mediated toxicity of AFB1 in the cells and might, therefore, offer a potent chemopreventive effect against procarcinogens activated by CYP4502B1.

[trouble]

I'll forgo additional damning posts, because ScottL is my freind.

Before you post ona supplement, check the recent literature base please.

[trouble]

Comfortable Pants 'n Thermolife are *more* than vidicated in the face of baseless critcism, as suggested by the aforementioned studies...its a little ahead of the curve..if you're not Indo-Asian, that is, as those folk been on to this little secret for quite some time (say, 500+ yrs).

[stellar]

The initial question phrased in the URL below:

"Consequences of inhibiting Cytochrome P450?"
http://tinyurl.com/omq2g


It's subsequent replies, all in expanded form:

http://tinyurl.com/ph4pj

http://tinyurl.com/o2o35

http://tinyurl.com/movpk

http://tinyurl.com/llg5r



This chart was particularly interesting (from the last post in that newsgroup thread):

Here are the references for the data in the table I previously posted.
I have added table salt.

> This is the table I compiled from a variety of sources, most of which
> I have references for and will post when I organize. D means
> decreases, or inhibits, and I means increases or activates the P450's.
> Hu means the study was on in humans, or at least on humans cells. I
> can't remember which.

> P-450 EFFECTS OF OTHER SUBSTANCES

Salt D
> Angelica Dihurica D
> ascorbyl palmitate D 600mg/day Hu
> benzyl isothiocyanate D
> (a cruciferous vegetable extract)
> Brussel sprouts I
> Cat's claw D
> Chamomile D
> Cholesterol I
> Chinese Medicines (many) D
> Danshen D
> Diesel exhaust I
> Echinacea D
> Ethanol I+D
> Evening Primrose oil (cis linoleic acid) <10
> Fat I
> Flavone D .15 Hu
> Garlic (allicin) D
> <10
> Ginseng D
> Ginkoe Biloba (ginkgolic acids I and II) D <10
> Grape fruit D 300ml/day
> Green tea D 75 Hu
> Goldenseal D
> Kava D
> <10
> Lycorice D
> Lipoic acid D .25g/kg in fish
> Meat, fried I
> Menthol D
> Hu
> Milk Thistle D
> Naringin D
> Peppermint oil D
> 600mg/day Hu
> Piperine D
> Quercetin D
> Resveratrol D 11
> Rutaecarpine (Chinese supplement) D
> 39nmole
> St John's Wort D .5 to 1 for certain
> components
> Tangeretin D .16Hu
> Vitamin A D
> Vitamin D I
> Wild Cherry D

[liorrh]

...

So its good for people with tumors or that must have some drugs in them.

Hooray?

Some of us kinda like our phase I's. you know, the thought of that burned burger ending up in my heart, brain. yuck.

Bioperine has its uses for sure. like nerve gas. Still, stuffing it in formulae for people without cancer or specific requirement as such is not adviseable. Phase I are too importnat in the industrialized, junkstuffed world.

[liorrh]

I read that long time ago stellar. good and long read. there has been more data out since, basically agreeing with it.
too bad that board is not active anymore.

[DCbuilder]

I am contemplating a 20 to 30 day cycle of Ecdysten. Each capsule contains 5 mg of Bioperine, and you are to take 9 per day.

That's 45mg of Bioperine per day for 30 days = 1350 mg over 30 days.

Would you consider this quantity of Bioperine in 30 days unwise or potentially unsafe?

[eclypz]

should I stop putting pepper on my eggs in the morning?

[trouble]

"NOEL dose = 1.12 mg of piperine per kg body weight "

No problem with this dosage. I've posted ample evidence that the supposed liver cytochrome P450 toxicity cited at the beginning of this thread was bullshit. Some don't understand, obviously, why upregulation of ETC might not be their best interests.

Its inclusion in the 20-edysten product should not pose a concern for adverse risk.

[Section 8]

Maybe I should have read the actual post, or not been so glib. More to the point, my problem is not with bioperine as such, but what it is generally used for, i.e. as an adjunct to laundry list supplement stacks with the intention of increasing bioavailability / slowing down clearance rates. Especially when said laundry list includes herbal extracts that contain god knows how many active constituents that haven't been properly studied to assess their effects on their own, let alone in conjunction with a bunch of other things.

[stellar]

should I stop putting pepper on my eggs in the morning?

LOL.

I take my Curcumin with pepper.

[Catshmat]

Trouble, you are super cool...


...You need to know.

[shpongled]

Maybe I should have read the actual post, or not been so glib. More to the point, my problem is not with bioperine as such, but what it is generally used for, i.e. as an adjunct to laundry list supplement stacks with the intention of increasing bioavailability / slowing down clearance rates. Especially when said laundry list includes herbal extracts that contain god knows how many active constituents that haven't been properly studied to assess their effects on their own, let alone in conjunction with a bunch of other things.

I agree.

As for the studies posted above, I can go dig up 100 abstracts that will make any substance look like a wonder drug. You have to contextualize them.

[Josh]

I agree.

As for the studies posted above, I can go dig up 100 abstracts that will make any substance look like a wonder drug. You have to contextualize them.

I agree

[liorrh]

I agree

I agree;)

since the action of bioperine is 90-120 minutes is support trouble's idea of taking it near the end of the workout, and only then, and not eat any carcinogenic thingis or be in a poluted environment during that time.

sounds good?

[Unregistered]

So, from reading the forum in general and the thermogum write up, I think the concerns in this topic are dropped?

Also found this (although from india):

Crit Rev Food Sci Nutr. 2007;47(8):735-48.

Black pepper and its pungent principle-piperine: a review of diverse physiological effects.
Srinivasan K.

Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, India. ksri.cftri@gmail.com

Black pepper (Piper nigrum) is one of the most widely used among spices. It is valued for its distinct biting quality attributed to the alkaloid, piperine. Black pepper is used not only in human dietaries but also for a variety of other purposes such as medicinal, as a preservative, and in perfumery. Many physiological effects of black pepper, its extracts, or its major active principle, piperine, have been reported in recent decades. Dietary piperine, by favorably stimulating the digestive enzymes of pancreas, enhances the digestive capacity and significantly reduces the gastrointestinal food transit time. Piperine has been demonstrated in in vitro studies to protect against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species. Black pepper or piperine treatment has also been evidenced to lower lipid peroxidation in vivo and beneficially influence cellular thiol status, antioxidant molecules and antioxidant enzymes in a number of experimental situations of oxidative stress. The most far-reaching attribute of piperine has been its inhibitory influence on enzymatic drug biotransforming reactions in the liver. It strongly inhibits hepatic and intestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase. Piperine has been documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals by this very property. Piperine's bioavailability enhancing property is also partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border. Although initially there were a few controversial reports regarding its safety as a food additive, such evidence has been questionable, and later studies have established the safety of black pepper or its active principle, piperine, in several animal studies. Piperine, while it is non-genotoxic, has in fact been found to possess anti-mutagenic and anti-tumor influences.