7 replies to this topic

[nootropi]

Rizzer said he was thinking about ordering some of this. I did a bit of research on it.

Here are some PEER REVIEWED articles of interest I found at the Bioperine source site

Planta Med. (1998) 64(4):353-356

INFLUENCE OF PIPERINE ON THE PHARMACOKINETICS OF CURCUMIN IN ANIMALS AND HUMAN VOLUNTEERS.

G. Shoba, D. Joy, T. Joseph, M. Majeed, R. Rajendran and P.S. Srinivas

ABSTRACT

The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilized because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. 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. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02) and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g 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 (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h); the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.





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Nutrition Research (1999) 19(3) 381-388

PIPERINE, AN ALKALOID DERIVED FROM BLACK PEPPER, INCREASES SERUM RESPONSE OF BETA-CAROTENE DURING 14-DAYS OF ORAL BETA-CAROTENE SUPPLEMENTATION

Vladimir Badmaev, M.D., Ph.D., Muhammed Majeed, Ph.D. and Edward P. Norkus Ph.D.



ABSTRACT

The effectiveness of an extract from the fruit of black pepper, consisting of a minimum of 98% pure alkaloid piperine was evaluated for its ability to improve serum response of beta-carotene during oral supplementation using a double-blind, crossover study design. Subjects were randomly selected to ingest a daily beta-carotene dose (15 mg) either with 5 mg of piperine or placebo during each of two 14-day supplementation periods. Inter-subject variability in pre-supplementation serum beta-carotene levels was minimized by limiting the selection of volunteers to healthy adult males with fasting serum beta-carotene values < 20 mcg/dL. The results indicate that significantly greater increases (p < 0.0001) in serum beta-carotene occurred during supplementation with beta carotene plus piperine (49.8±9.6 mcg/dL vs. 30.9±5.4 mcg/dL) compared to beta-carotene plus placebo. Supplementation with beta-carotene plus piperine for 14 days produced a 60% greater increase in area under the serum beta- carotene curve (AUC) than was observed during supplementation with beta-carotene plus placebo. We suggest that the serum response during oral beta-carotene supplementation is improved through non-specific, thermogenic property(s) of piperine described in this paper as thermonutrient action.


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J. Nutr. Biochem. (2000) 11: 109-113

PIPERINE DERIVED FROM BLACK PEPPER INCREASES THE PLASMA LEVELS OF COENZYME Q10 FOLLOWING ORAL SUPPLEMENTATION

Vladimir Badmaev, M.D., Ph.D., Muhammed Majeed, Ph.D., and Lakshmi Prakash, Ph.D.



ABSTRACT

An extract from the fruits of black pepper consisting of a minimum of 98% pure piperine was evaluated in a clinical study using a double-blind design. The relative bioavailability of 90 mg and 120 mg of coenzyme Q10 administered in a single dose experiment or in separate experiments for 14 and 21 days with placebo or with 5 mg of piperine was determined by comparing measured changes in plasma concentration. The inter-subject variability was minimized by limiting the selection of individuals to healthy adult male volunteers with (pre-supplementation) fasting coenzyme Q10 values between 0.30 and 0.60 mg/L. The results of a single dose study and the 14-day study indicate smaller, but not significant, increases in plasma concentrations of coenzyme Q10 in the control group compared to the group receiving coenzyme Q10 with a supplement of piperine. Supplementation of 120 mg of coenzyme Q10 with piperine for 21 days produced a statistically significant (p=0.0348), approximately 30% greater, area under the plasma curve (AUC) than observed during supplementation with coenzyme Q10 plus placebo. It is postulated that the bioenhancing mechanism of piperine to increase plasma levels of supplemental coenzyme Q10 is nonspecific and possibly based on its description in the literature as a thermonutrient.

The reason that this particular supplement may be of interest is because several of us (myself included) take 40 or more supplements daily, so several of these may be competing for absorption; so anything that will increase bioavailability is appreciated.

Edited by nootropi, 04 December 2004 - 06:57 PM.

[scottl]

I believe that the morelife guy...Paul Wakfer had some comments about this and I'm not sure that it was as simple as it appears. I don't remember if it was in the old days when he was mod at the LEF.org board (you can still search those old posts there) or more recently at morelife yahoo.

[AORsupport]

Rizzer said he was thinking about ordering some of this.  I did a bit of research on it.

The reason that this particular supplement may be of interest is because several of us (myself included) take 40 or more supplements daily, so several of these may be competing for absorption; so anything that will increase bioavailability is appreciated.[/b]

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.

[hyoomen]

That's a shame, as I'm always interested in turmeric/curcumin literature. A friend with CF was heartened by some of the new research regarding turmeric, so anything we can find to potentiate its effects are a big plus.

[nootropi]

R
izzer said he was thinking about ordering some of this.  I did a bit of research on it.

The reason that this particular supplement may be of interest is because several of us (myself included) take 40 or more supplements daily, so several of these may be competing for absorption; so anything that will increase bioavailability is appreciated.[/b]

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.

While this may be important information, I personally would not want to take anything that has any toxins in it in the first place. I think bioperine should be taken with safe supplements to increase bioavaiablility; as has already it has been proven to increase bioavailablity.

[AORsupport]

Rizzer said he was thinking about ordering some of this.  I did a bit of research on it.

The reason that this particular supplement may be of interest is because several of us (myself included) take 40 or more supplements daily, so several of these may be competing for absorption; so anything that will increase bioavailability is appreciated.[/b]

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.

... piperine enhances the bioavailability of some substances ... [primarily via]  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)...

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.

[Documentation snipped]

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.

While this may be important information, I personally would not want to take anything that has any toxins in it in the first place.  I think bioperine should be taken with safe supplements to increase bioavaiablility; as has already it has been proven to increase bioavailablity.

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

[nootropi]

AORsupport: What if I was to say, take 1 milligram with my daily supplement pills? What I am wondering is if I decided to ingest a low dose of bioperine with my daily supplement regime of 30 or so supplements; and all the products I ingest are food grade or better; isn't it "likely" that several supplements will have increased bioavailablity? So wouldn't the "good stuff" that the bioperine made more bioavailable contra-affect the " bad stuff?" Now I am saying a LOW dose like 1 or 2 milligrams.

Thank you, AORsupport. [thumb] Once again, I appreciate AOR's integrity with respect to quality control of nutritional supplements; I do hope you still emply as rigourous quality control procedures as you have in the past. And, next time you purchase and LE supplement in kilogram quantities, please let me know what the supplement is, where you are having it tested, and permit me to see a copy of the assay results from a third party laboratory; then I would certainly be interested in purchasing in one kilogram or more lots. I think you could do the Immortality Institute FULL members a service by allowing us to purchase supplements that you carry in bulk quantites (with say akilgram minimum; that way you could offset the costs of the third party independent testing )).

Take care.

[nootropi]

AORsupport:  What if I was to say, take 1 milligram with my daily supplement pills?  What I am wondering is if I decided to ingest a low dose of bioperine with my daily supplement regime of 30 or so supplements; and all the products I ingest are food grade or better; isn't it "likely" that several supplements will have increased bioavailablity?  So wouldn't the "good stuff" that the bioperine made more bioavailable contra-affect the " bad stuff?"  Now I am saying a LOW dose like 1 or 2 milligrams.

Thank you, AORsupport. [thumb]  Once again, I appreciate AOR's integrity with respect to quality control of nutritional supplements; I do hope you still emply as rigourous quality control procedures as you have in the past.  And, next time you purchase and LE supplement in kilogram quantities, please let me know what the supplement is, where you are having it tested, and permit me to see a copy of the assay results from a third party laboratory; then I would certainly be interested in purchasing in one kilogram or more lots.  I think you could do the Immortality Institute FULL members a service by allowing us to purchase supplements that you carry in bulk quantites (with say akilgram minimum; that way you could offset the costs of the third party independent testing )).

Take care.

Bump