35 replies to this topic

[malbecman]

I know some people on this board don't like using piperine but the increase in AUC and (C(max)) was pretty significant in this mouse study......

On a side note, I am really seeing a significant increase in the # of resveratrol papers showing up weekly in PubMed. I"m just trying to keep up at this point.



Mol Nutr Food Res. 2011 Jun 29. doi: 10.1002/mnfr.201100117. [Epub ahead of print]
Enhancing the bioavailability of resveratrol by combining it with piperine.
Johnson JJ, Nihal M, Siddiqui IA, Scarlett CO, Bailey HH, Mukhtar H, Ahmad N.
Source
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Abstract
Scope: Resveratrol (3,5,4'-trihydroxystilbene) is a phytoalexin shown to possess a multitude of health-promoting properties in pre-clinical studies. However, the poor in vivo bioavailability of resveratrol due to its rapid metabolism is being considered as a major obstacle in translating its effects in humans. In this study, we examined the hypothesis that piperine will enhance the pharmacokinetic parameters of resveratrol via inhibiting its glucuronidation, thereby slowing its elimination. Methods and results: Employing a standardized LC/MS assay, we determined the effect of piperine co-administration with resveratrol on serum levels resveratrol and resveratrol-3-O-β-D-glucuronide in C57BL mice. Mice were administered resveratrol (100 mg/kg; oral gavage) or resveratrol (100 mg/kg; oral gavage)+piperine (10 mg/kg; oral gavage), and the serum levels of resveratrol and resveratrol-3-O-β-D-glucuronide were analyzed at different times. We found that the degree of exposure (i.e. AUC) to resveratrol was enhanced to 229% and the maximum serum concentration (C(max) ) was increased to 1544% with the addition of piperine. Conclusion: Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol. However, further detailed research is needed to study the mechanism of improved bioavailability of resveratrol via its combination with piperine as well as its effect on resveratrol metabolism.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID: 21714124

[Anthony_Loera]

malbecman

that was a good find. We will probably do something with it thanks,
however the 10mg per kg seems a bit high for piperine for a human.

A

[niner]

that was a good find. We will probably do something with it thanks,
however the 10mg per kg seems a bit high for piperine for a human.

100mg/kg is a very large dose of resveratrol, and it's in mice, too. It would be interesting to see how it translated to normal doses in humans.

[sagecucumber]

I take a curcumin supplement that also contains 3.75mg Piperine. I've found if I take it in the morning with resveratrol I will have a headache for most of the day. I've done it enough times to know for sure it's related to that combination of supplements so i take the curcumin/piperine at night. I can't for sure attribute the reaction just to the piperine/resveratrol combo but i kind of think it is.

[maxwatt]

Piperine can cause hypotension due to its blood pressure lowering and vasomodulator effects. Cranial hypotension can cause headaches in some people. Perhaps the effect is aggravated by resveratrol.

[2tender]

Piperine was in a bunch of supplements years ago. The conclusion of supplement users and producers was that it really didnt help. There were more side effects, than anything, on the other hand there were good anecdotal reports and in some instances the amount was so small that it didnt cause any negative effects. I think straight resveratrol is best, at minimum doses.

[CCS]

Piperine just gets it past the intestines. It still is destroyed by the liver before serum levels can see an increase.

To bypass the liver, why not take it rectally, dissolved in warm butter and then chilled to a solid suppository? The liver would destroy it soon, but not after it makes a full first pass.

I'm surprised no studies tried this route. How confident are we that we actually want to get higher serum resveratrol levels? Think it is safe if it has not been done before?

[malbecman]

Well, here is Figure 1 as an attachment showing both the resveratrol and glucuronide timecourses for both straight resveratrol and resveratrol+piperine admin. You still get a pretty nice peak of just resveratrol
at the beginning of the timecourse.

Attached Files

•  Fig1.tiff   90.2KB   182 downloads

Edited by malbecman, 05 July 2011 - 09:47 PM.

[CCS]

Well, here is Figure 1 as an attachment showing both the resveratrol and glucuronide timecourses for both straight resveratrol and resveratrol+piperine admin. You still get a pretty nice peak of just resveratrol
at the beginning of the timecourse.

From that graph I'll definitely be using some piperine too.

[maxwatt]

This is for mice. Human metabolism is different enough for the enzymes involved in these pathways, I'd want to see the results for human blood levels. But I expect we'll be getting reports of effects in this group soon.

Edited by maxwatt, 06 July 2011 - 10:06 AM.

[bixbyte]

Both of us have been taking 10 mg piperine concurrent with AM RES for many years.
My wife and I are Still here.
The RES does appear to have made us both very athletic.
Anyone else notice a better body?

[bixbyte]

Both of us have been taking 10 mg piperine concurrent with AM RES for many years.
My wife and I are Still here.
The RES does appear to have made us both very athletic.
Anyone else notice a better body?

After performing my own research, Tody I have increased our Piperine Dose to 20 Milligrams.
I am not a mouse, this mouse study trialed suggests the ratio approx 10 to 1.
Here is my logic:
200 milligrams of RES with 20 Milligrams of Piperine in order to produce a similar Resveratrol
blood peak plasma level that was in the mouse chart. (NICE SPIKE)
Increase the Bioavailabilty of the Resveratrol with a supplement that costs me $5.20 for 120 tablets.

[bixbyte]

Well, here is Figure 1 as an attachment showing both the resveratrol and glucuronide timecourses for both straight resveratrol and resveratrol+piperine admin. You still get a pretty nice peak of just resveratrol
at the beginning of the timecourse.

Chart certainly appears to display a 4X times increase benefit spike Res plasma level for 0 to 30 minutes.
Piperine costs me $5.19 for 120 tabs 10 milligram.

[hav]

Been capping my own resveratrol, polydatin, and luteolin combo but worried that the mere 200 mg of Quercetin I could squeeze in there might not be enough to enhance absorption. Just ordered some 95% piperine powder at $2.50/gram. I've always shied away from black pepper because it's such an irritant but I understand that extracted piperine does not have that quality. Figuring I could cut back on the quercetin for 10 mg of piperine. Or should I just drop the quercetin completely?

Howard

[maxwatt]

I would drop the quercetin, luteolin is several times as effective as a sulfotransferase inhibitor if you feel you need one.

[bixbyte]

Been capping my own resveratrol, polydatin, and luteolin combo but worried that the mere 200 mg of Quercetin I could squeeze in there might not be enough to enhance absorption. Just ordered some 95% piperine powder at $2.50/gram. I've always shied away from black pepper because it's such an irritant but I understand that extracted piperine does not have that quality. Figuring I could cut back on the quercetin for 10 mg of piperine. Or should I just drop the quercetin completely?

Howard

____________________________________________________________

Hi Howard,
Wife and I dropped the quercetin years ago.
The mouse chart certainly appears to display 4 X times higher blood plasma peaks with Res and much higher with Polydatin - are cut with piperine.
Been taking 10 mg piperine for years.
4 days on 20 milligrams of piperine and costs pennies to elevate RES plasma levels.
I might up the piperine to 50 milligrams.
Anecdotal evidence after 7 years of upping RES,
some characteristics like an athlete, it is fun to look like athletes in our late 50's.
No Olympic try outs for me.

Have Fun,

Alex

_______________________________________________

[hav]

Thanks, maxwatt and bixbyte. Will drop the quercetin. But I think I'll stick with 10 mg/cap of piperine for now since I'm thinking of taking 1 cap 2 or 3 times daily.

Howard

[gomesbs]

I think one of the cheapest pure resveratrol brands on pricewatch have been adding piperine on their formulation for ages:

http://www.nutraplan...0-capsules.html

I've used it sometimes, didn't notice anything different compared to other pure forms without piperine, same dosage, but I can't recall clearly...

[bixbyte]

This is for mice. Human metabolism is different enough for the enzymes involved in these pathways, I'd want to see the results for human blood levels. But I expect we'll be getting reports of effects in this group soon.

WE NEED TO SEE THE CLINICAL TRIAL RESULTS. HUMAN.

http://clinicaltrial...how/NCT01331382

[bixbyte]

NO RESULTS FROM HUMAN STUDY WITH PIPERINE.
This is all I can find:


http://druginfo.nlm....QV1=RESVERATROL


Drug Name: Resveratrol [show more names]
Description: NCI: A phytoalexin derived from grapes and other food products with antioxidant and potential chemopreventive activities. Resveratrol induces phase II drug-metabolizing enzymes (anti-initiation activity); mediates anti-inflammatory effects and inhibits cyclooxygenase and hydroperoxidase functions (anti-promotion activity); and induces promyelocytic leukemia cell differentiation (anti-progression activity), thereby exhibiting activities in three major steps of carcinogenesis. This agent may inhibit TNF-induced activation of NF-kappaB in a dose- and time-dependent manner. ... (NCI Thesaurus)
Categories: Analgesics [show more categories]

[niner]

WE NEED TO SEE THE CLINICAL TRIAL RESULTS. HUMAN.

Here ya go! Sadly, despite what was claimed in the trial documentation (where they also called resveratrol an "alkaloid"...), there is no mention whatsoever of piperine in the resulting paper. It appears that they made a last minute change from res + piperine to a higher dose of res. WTF?

Am J Clin Nutr. 2010 Jun;91(6):1590-7. Epub 2010 Mar 31. FREE FULL TEXT
Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation.
Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, Haskell CF.

Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle upon Tyne, United Kingdom. david.kennedy@unn.ac.uk <david.kennedy@unn.ac.uk>

BACKGROUND:

The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses, modulate nitric oxide synthesis, and promote vasodilation, which thereby improves blood flow. Resveratrol may therefore modulate aspects of brain function in humans.
OBJECTIVE:

The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults.
DESIGN:

In this randomized, double-blind, placebo-controlled, crossover study, 22 healthy adults received placebo and 2 doses (250 and 500 mg) of trans-resveratrol in counterbalanced order on separate days. After a 45-min resting absorption period, the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min. Cerebral blood flow and hemodynamics, as indexed by concentration changes in oxygenated and deoxygenated hemoglobin, were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy. The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort (n = 9).
RESULTS:

Resveratrol administration resulted in dose-dependent increases in cerebral blood flow during task performance, as indexed by total concentrations of hemoglobin. There was also an increase in deoxyhemoglobin after both doses of resveratrol, which suggested enhanced oxygen extraction, that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance. Cognitive function was not affected. Resveratrol metabolites were present in plasma throughout the cognitive task period.
CONCLUSION:

These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables.

PMID: 20357044

[rikelme]

Here is another study which will show if the resveratrol bioavailability is increased by piperin in humans (no results have been published yet):
Resveratrol With or Without Piperine to Enhance Plasma Levels of Resveratrol

There is some evidence that when resveratrol (a substance which is found in red grapes, peanuts and chocolate) is combined with Piperine (a substance found in pepper) it is more effective in fighting cancer. The purpose of this study is to see if resveratrol in combination with piperine is more effective than taking resveratrol alone. Since investigators don't know what dose of piperine to use in combination with resveratrol, two different doses of piperine will be studied.
Twenty-four participants, equal numbers of males and females, will receive a single dose of resveratrol (2.5 grams) without piperine, resveratrol (2.5 grams) with piperine (5 mg), or resveratrol (2.5 grams) with piperine (25 mg).

[malbecman]

Nice find! Hopefully we will see the results soon since it was estimated to be finished last March.....
Estimated Study Completion Date: March 2012

Here is another study which will show if the resveratrol bioavailability is increased by piperin in humans (no results have been published yet):
Resveratrol With or Without Piperine to Enhance Plasma Levels of Resveratrol

There is some evidence that when resveratrol (a substance which is found in red grapes, peanuts and chocolate) is combined with Piperine (a substance found in pepper) it is more effective in fighting cancer. The purpose of this study is to see if resveratrol in combination with piperine is more effective than taking resveratrol alone. Since investigators don't know what dose of piperine to use in combination with resveratrol, two different doses of piperine will be studied.
Twenty-four participants, equal numbers of males and females, will receive a single dose of resveratrol (2.5 grams) without piperine, resveratrol (2.5 grams) with piperine (5 mg), or resveratrol (2.5 grams) with piperine (25 mg).

[katrina]

Ok so it wasn't my imagination. I felt that the 400 T-Rez I took years ago always worked LOADS better than the 500 Revgenetics. And guess what the T-Rez has? Piperine... Just recently I started taking resveratrol again, but the T-Rex is out of stock. I wonder if this is permanent? Sigh...

[dz93]

So Trans-Res contains Piperine? Or will I have to make sure wherever I'm getting from states it contains piperine? And where can I find a good source of powdered trans-res? Thanks!

[maxwatt]

Ground black pepper contains enough piperine that a capsule full should have the effect you thiink you need. Might irritate the stomach by itself though.

[zorba990]

I thought piperine induced a sort of leaky gut syndrome and was undesireable. Has the thinking on this changed?

[cudBwrong]

Here ya go! Sadly, despite what was claimed in the trial documentation (where they also called resveratrol an "alkaloid"...), there is no mention whatsoever of piperine in the resulting paper. It appears that they made a last minute change from res + piperine to a higher dose of res. WTF?

Am J Clin Nutr. 2010 Jun;91(6):1590-7. Epub 2010 Mar 31. FREE FULL TEXT
Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation.
Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, Haskell CF.

Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle upon Tyne, United Kingdom. david.kennedy@unn.ac.uk <david.kennedy@unn.ac.uk>

BACKGROUND:

The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses, modulate nitric oxide synthesis, and promote vasodilation, which thereby improves blood flow. Resveratrol may therefore modulate aspects of brain function in humans.
OBJECTIVE:

The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults.
DESIGN:

In this randomized, double-blind, placebo-controlled, crossover study, 22 healthy adults received placebo and 2 doses (250 and 500 mg) of trans-resveratrol in counterbalanced order on separate days. After a 45-min resting absorption period, the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min. Cerebral blood flow and hemodynamics, as indexed by concentration changes in oxygenated and deoxygenated hemoglobin, were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy. The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort (n = 9).
RESULTS:

Resveratrol administration resulted in dose-dependent increases in cerebral blood flow during task performance, as indexed by total concentrations of hemoglobin. There was also an increase in deoxyhemoglobin after both doses of resveratrol, which suggested enhanced oxygen extraction, that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance. Cognitive function was not affected. Resveratrol metabolites were present in plasma throughout the cognitive task period.
CONCLUSION:

These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables.

PMID: 20357044

I think it's just silly to be testing for cognitive improvements based on a single dose of resveratrol. It is interesting that they found blood flow differences.

Think about what resveratrol does for the plants that synthesize it. It's produced in response to stress and injury. It may deter pathogens, but since it's produced in response to non-pathogen injury, it also may help the plant repair itself.

Repairs take time. Neural networks take time, to build and train themselves.

Clinical trials need to look for effects over a long-term period of continuous administration.

[cudBwrong]

Here is a recent, free full text review article on bioavailability enhancers, including piperine:

https://www.ncbi.nlm...les/PMC3634921/

[cudBwrong]

Regarding the study in the original post:

Mol Nutr Food Res. 2011 Jun 29. doi: 10.1002/mnfr.201100117. [Epub ahead of print]
Enhancing the bioavailability of resveratrol by combining it with piperine.
Johnson JJ, Nihal M, Siddiqui IA, Scarlett CO, Bailey HH, Mukhtar H, Ahmad N.

One possibly confounding element is the nonlinear response of the liver to resveratrol. The experimental group received resveratrol plus piperine. The control group received only resveratrol. The bioavailability of resveratrol in the experimental group was higher, but was that due specifically to the piperine, or was it just due to the fact that the liver had more work to do, and was "too busy" to process the resveratrol in a timely fashion? In other words, could the same result be achieved with a dose of anything that makes the liver busy, including a higher resveratrol dose?

I think that there is an effect which is specific to piperine, for several reasons. First, they already are at a very high resveratrol dose, about 7 grams for a human on a mass-equivalent basis. On a surface area equivalent basis, it is about 24 grams.

The main reason is the dramatic difference in measures of availability, even the more conservative one, AUC, area under the concentration curve, of 229%.

Finally, there are many studies that show specific biological effects of piperine, alone or in combination with other substances. It seems to me that piperine is making a specific contribution to bioavailability.

Edited by cudBwrong, 14 May 2013 - 08:01 PM.