LONGECITY

I was very curious about AOR's resveratrol formulation so I emailed them. The following is my email and their response... Very interesting!

***My Email***

To Whom It May Concern,

I am interested in your product and respect your company, but I have a few questions on your formula.

First: Why did you add Luteolin? Have you found that blocking some of the sulfation and glucoronidation of Resveratrol can be achieved by adding this particular flavonoid rather than say more Quercetin or another flavonoid?

Second: Why did you add Piper Nigrum (aka bioperine) as this substance can potentially allow carcinogens to be absorbed better. Furthermore there seems to be no mechanism by which it would improve Resveratrol absorption.

Best Regards,

G.E.

***Response***

"ludo@aor.ca"

Good morning,

Our new resveratrol formula contains Luteolin because it is a more
powerful inhibitor of sulfation than other flavanoids, quercetin included.
Piperin also helps to block the breakdown of the resveratrol in the liver,
thereby increasing the levels in the blood. There also seems to be an
increased absorption in the gastrointestinal tract with the addition of
piperine.
I understand your concern with piperine and cancer but studies seem to
indicate that piperine may help prevent cancer:
http://www.ncbi.nlm....l=pubmed_docsum

I hope this helps, if you have any other questions, please do not hesitate
to contact us.

Thank you for your interest in AOR,

AOR technical support


Very interesting, huh?...... Discuss
Edited by edward, 13 April 2007 - 02:41 PM.

Here is the label:
Trans-Resveratrol (in oxygen, pH, and
light-resistant beadlets) .............................. 100 mg
Luteolin ......................................................... 20 mg
Quercetin ...................................................... 51 mg
Vitamin C (Ascorbic Acid) .................................. 40 mg
Piper Nigrum ................................................... 20 mg

--------------------------------------------------------------------------

Luteolin is not cheap either. Interesting email, thanks for sharing!

AOR also states the following:

Non-medicinal ingredients: EDTA, rosemary extract. Capsule; hypromellose, sorbitol, silicon dioxide, titanium dioxide, water.


AOR guarantees that no ingredients not listed on the label have been added to the product.


Based on these statements they are indicating 100% trans-Resveratrol!

I understand your concern with piperine and cancer but studies seem to
indicate that piperine may help prevent cancer:
http://www.ncbi.nlm....l=pubmed_docsum

Wouldn't this be a rather bold statement based on the study that is presented?

Something else regarding cancer that is interesting on its own, but quite different, involving Piper Nigrum (and resveratrol plus a bunch of other flavonoids), that cannot account for AOR's statement regarding Piper Nigrum:

Chemosensitization and radiosensitization of tumors by plant polyphenols.Garg AK, Buchholz TA, Aggarwal BB.
Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

The treatment of cancer with chemotherapeutic agents and radiation has two major problems: time-dependent development of tumor resistance to therapy (chemoresistance and radioresistance) and nonspecific toxicity toward normal cells. Many plant-derived polyphenols have been studied intently for their potential chemopreventive properties and are pharmacologically safe. These compounds include genistein, curcumin, resveratrol, silymarin, caffeic acid phenethyl ester, flavopiridol, emodin, green tea polyphenols, piperine, oleandrin, ursolic acid, and betulinic acid. Recent research has suggested that these plant polyphenols might be used to sensitize tumor cells to chemotherapeutic agents and radiation therapy by inhibiting pathways that lead to treatment resistance. These agents have also been found to be protective from therapy-associated toxicities. How these polyphenols protect normal cells and sensitize tumor cells to treatment is discussed in this review. Antioxid. Redox Signal. 7, 1630-1647.

PMID: 16356126 [PubMed - indexed for MEDLINE]

I also found this (If anyone 1s able to dig-up this one in its complete form I would be interested):

Screening of the inhibitory effect of vegetable constituents on the aryl hydrocarbon receptor-mediated activity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.Amakura Y, Tsutsumi T, Sasaki K, Yoshida T, Maitani T.
Division of Foods, National Institute of Health Sciences, Tokyo, Japan. amakura@nihs.go.jp

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

PMID: 14646185 [PubMed - indexed for MEDLINE]

This one seems to address the cytochrome issue, but the conclusion is a bit confusing since it seems to suggest some sort of balancing act... (Ok, Í am a bit confused not being a medical professional )
As far as I understand (or understood) it is the inhibition of cytochrome P4502B1 that enables toxins not to be "excreted" by the liver?

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.
Regional Research Laboratory, C.S.I.R., Jammu-Tawi, India.

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%. The 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.

PMID: 9421252 [PubMed - indexed for MEDLINE]

Where's the hard evidence for the mistrust of piperine?
Edited by brainbox, 13 April 2007 - 10:09 PM.

This one seems to address the cytochrome issue, but the conclusion is a bit confusing since it seems to suggest some sort of balancing act... (Ok, Í am a bit confused not being a medical professional )
As far as I understand (or understood) it is the inhibition of cytochrome P4502B1 that enables toxins not to be "excreted" by the liver?

There are two phases of detoxification. Phase I is where the cytochrome P450 system makes the molecule conjugable, but also nastier. Phase II conjugates the nastier thing with glutathione, sulfate, glycine, glucuronide, etc. to make it water soluble and excretable. So having Phase I proceeding without adequate Phase II cofactors to mop up the debris is a bad thing.

I have the paper as a PDF if you need it. PM me.

I also found this (If anyone 1s able to dig-up this one in its complete form I would be interested):

Screening of the inhibitory effect of vegetable constituents on the aryl hydrocarbon receptor-mediated activity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.Amakura Y, Tsutsumi T, Sasaki K, Yoshida T, Maitani T.
Division of Foods, National Institute of Health Sciences, Tokyo, Japan. amakura@nihs.go.jp

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

PMID: 14646185 [PubMed - indexed for MEDLINE]

There's a lot to chew on here. I've generally been impressed with the level of science at AOR, yet I've also seen a level of hype and occasional scientific illiteracy on their web site that give me pause. So far I've chalked it up to a disconnect between the people in the lab and the copy writers (which is a problem in itself). At this point, I think their approach to the enhancement of resveratrol bioavailability is a mixed bag. Here's what I've come up with.

The Problem: Resveratrol's bioavailability is poor due to extensive conjugation in the liver and also in the gut. This is primarily sulfation but also glucuronidation.

Not a Problem: The absorption of resveratrol from the gut is pretty good- something like 60-70%, so it doesn't seem like much help is needed there. The resveratrol molecule is already studded with hydroxyls, so it does not need to be oxidized further by P450s; P450s are not really an issue here.

AOR's approach to improving the bioavailability of resveratrol:

Quercetin: An extremely potent inhibitor of resveratrol sulfation in both liver and gut, with an IC50 of 12 and 15 picomolar, respectively. (De Santi, et al. PMID: 10923862) This makes perfect sense as an adjuvant. Why 51 mg? Sounds more "scientific" than 50 mg? (OK, I'm being cynical...)

Luteolin: There's some (weak) evidence that it's a pGp inhibitor. (pGp is Permeability GlycoProtein, a xenobiotic efflux pump. It acts to pump drugs out of your blood and back into the intestine.) PGp only works for certain compounds, and I don't think resveratrol is one of them, so luteolin probably doesn't do much there. Luteolin is also a multiple P450 inhibitor (see below). That's not going to help with resveratrol, although it might cause trouble with prescription drugs. I don't really see the point of the luteolin.

Drug Metab Dispos. 2007 Feb;35(2):185-8. Epub 2006 Nov 8.
The in vitro drug interaction potential of dietary supplements containing multiple herbal components.
Foti RS, Wahlstrom JL, Wienkers LC.
Biochemistry/Biophysics Group, Amgen Pharmacokinetics and Drug Metabolism, Seattle, Washington 98119, USA. rfoti@amgen.com
Herbal-based remedies are widely used as alternative treatments for a number of ailments. In addition, the use of products that contain both single and multiple herbal constituents is becoming increasingly common. The work described in this report examined the in vitro drug interaction potential for a commonly used herbal cold remedy reported to contain a mixture of eight herbal components. Experiments conducted in human liver microsomes exhibited significant inhibition (<10% of control activity remaining) of multiple cytochrome P450 (P450) isoforms, including CYP2B6, CYP2C9, and CYP2D6, by the herbal mixture. In an attempt to explain the observed P450 inhibition by the herbal mixture, individual active components were obtained and tested for inhibitory potency. Inhibition of multiple P450 activities by a single constituent, luteolin, was observed. Conversely, inhibition of a single isoform by several herbal components was noted for CYP2B6. Based on the data presented, it is concluded that mixtures of herbal components may exhibit multiple modes of P450 inhibition, indicating the potential for complex herbal-drug interaction scenarios to occur.
PMID: 17093003

Finally, they claim that luteolin is a more powerful inhibitor of sulphation than quercetin (and that's really saying something!) but according to the following, luteolin is not only not an inhibitor of sulphation, but it actually enhances glucuronidation 3-5 fold! That does not seem like what you want. Maybe resveratrol is a special case? I don't know what's up here.

Drug Metab Dispos. 2002 May;30(5):564-9. 
Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements.
Walle UK, Walle T.
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Recent studies in our laboratory in the human hepatic and intestinal cell lines Hep G2 and Caco-2 have demonstrated induction of UGT1A1 by the flavonoid chrysin (5,7-dihydroxyflavone) using catalytic activity assays and Western and Northern blotting. In the present study, we examined which features of the flavonoid structures were associated with induction of UGT1A1 and whether common drug-metabolizing enzyme inducers also produce this induction. We also determined whether flavonoid treatment affected sulfate conjugation and CYP1A1 activity. We used intact Hep G2 cells for these studies, with chrysin as the model substrate. Both glucuronidation and sulfation were measured. Hep G2 cells were pretreated for 3 days with 25 microM concentrations of 22 flavonoids (n = 4-12). Only four flavonoids demonstrated induction of glucuronidation similar to that of chrysin (i.e., 3-5-fold in the intact cells). These were acacetin, apigenin, luteolin, and diosmetin, all of which, like chrysin, are 5,7-dihydroxyflavones with varying substituents in the B-ring. 5-Hydroxy-7-methoxyflavone and 5-methyl-7-hydroxyflavone produced a modest 1.5 to 2-fold induction, whereas all other flavonoids examined were without effect. None of the flavonoids caused more than a modest change in sulfation activity (60-140% of control). In contrast, all tested 5,7-dihydroxyflavones and -flavonols induced CYP1A1 activity (ethoxyresorufin deethylation). Of seven common drug-metabolizing enzyme inducers only 3-methylcholanthrene and oltipraz showed modest induction of chrysin glucuronidation but not 2,3,7,8-tetrachlorodibenzo-p-dioxin or phenobarbital. Together, these results strongly suggest that the flavonoid induction of UGT1A1 is through a novel nonaryl hydrocarbon receptor-mediated mechanism.
PMID: 11950788

Piperine: This may be another pGp efflux pump inhibitor. (PMID: 16243320) It may alter gut permeability resulting in increased absorption of some drugs (PMID: 12046863). I don't consider either of these putative activities to be particularly relevant. However, it appears to be an inhibitor of glucuronidation, and this may well be useful. In rats, it inhibited glucuronidation of EGCG in the gut by 40%, but did nothing in liver cells. See below and also PMID: 8347144.

J Nutr. 2004 Aug;134(8):1948-52.  Links
Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in mice.Lambert JD, Hong J, Kim DH, Mishin VM, Yang CS.
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey, Piscataway, NJ 08854, USA. joshua_lambert@hotmail.com

(-)-Epigallocatechin-3-gallate (EGCG), from green tea (Camellia sinensis), has demonstrated chemopreventive activity in animal models of carcinogenesis. Previously, we reported the bioavailability of EGCG in rats (1.6%) and mice (26.5%). Here, we report that cotreatment with a second dietary component, piperine (from black pepper), enhanced the bioavailability of EGCG in mice. Intragastric coadministration of 163.8 micromol/kg EGCG and 70.2 micromol/kg piperine to male CF-1 mice increased the plasma C(max) and area under the curve (AUC) by 1.3-fold compared to mice treated with EGCG only. Piperine appeared to increase EGCG bioavailability by inhibiting glucuronidation and gastrointestinal transit. Piperine (100 micromol/L) inhibited EGCG glucuronidation in mouse small intestine (by 40%) but not in hepatic microsomes. Piperine (20 micromol/L) also inhibited production of EGCG-3"-glucuronide in human HT-29 colon adenocarcinoma cells. Small intestinal EGCG levels in CF-1 mice following treatment with EGCG alone had a C(max) = 37.50 +/- 22.50 nmol/g at 60 min that then decreased to 5.14 +/- 1.65 nmol/g at 90 min; however, cotreatment with piperine resulted in a C(max) = 31.60 +/- 15.08 nmol/g at 90 min, and levels were maintained above 20 nmol/g until 180 min. This resulted in a significant increase in the small intestine EGCG AUC (4621.80 +/- 1958.72 vs. 1686.50 +/- 757.07 (nmol/g.min)). EGCG appearance in the colon and the feces of piperine-cotreated mice was slower than in mice treated with EGCG alone. The present study demonstrates the modulation of the EGCG bioavailablity by a second dietary component and illustrates a mechanism for interactions between dietary chemicals.

PMID: 15284381

From my brief consideration of this, it looks like quercetin should help resveratrol bioavailability, perhaps a fair amount. Luteolin appears as though it should hurt more than help, and piperine looks like it might help some, but I'm not sure how much. What is needed here is for someone to give these compounds to human volunteers along with some resveratrol, stick a needle in their arm and quantitate things. I have a strong suspicion that that has not yet happened, unless maybe Sirtris did it, but they probably aren't talking. I'd like to hear more from AOR.

There's a lot to chew on here.  I've generally been impressed with the level of science at AOR, yet I've also seen a level of hype and occasional scientific illiteracy on their web site that give me pause.  So far I've chalked it up to a disconnect between the people in the lab and the copy writers (which is a problem in itself).  At this point, I think their approach to the enhancement of resveratrol bioavailability is a mixed bag.  Here's what I've come up with.

The Problem:  Resveratrol's bioavailability is poor due to extensive conjugation in the liver and also in the gut.  This is primarily sulfation but also glucuronidation.

Not a Problem: The absorption of resveratrol from the gut is pretty good- something like 60-70%, so it doesn't seem like much help is needed there.  The resveratrol molecule is already studded with hydroxyls, so it does not need to be oxidized further by P450s; P450s are not really an issue here.

AOR's approach to improving the bioavailability of resveratrol:

Quercetin:  An extremely potent inhibitor of resveratrol sulfation in both liver and gut, with an IC50 of 12 and 15 picomolar, respectively.  (De Santi, et al. PMID: 10923862)  This makes perfect sense as an adjuvant.  Why 51 mg?  Sounds more "scientific" than 50 mg?  (OK, I'm being cynical...)

Luteolin:  There's some (weak) evidence that it's a pGp inhibitor.  (pGp is Permeability GlycoProtein, a xenobiotic efflux pump.  It acts to pump drugs out of your blood and back into the intestine.)  PGp only works for certain compounds, and I don't think resveratrol is one of them, so luteolin probably doesn't do much there.  Luteolin is also a multiple P450 inhibitor (see below).  That's not going to help with resveratrol, although it might cause trouble with prescription drugs.  I don't really see the point of the luteolin.

Drug Metab Dispos. 2007 Feb;35(2):185-8. Epub 2006 Nov 8.
The in vitro drug interaction potential of dietary supplements containing multiple herbal components.
Foti RS, Wahlstrom JL, Wienkers LC.
Biochemistry/Biophysics Group, Amgen Pharmacokinetics and Drug Metabolism, Seattle, Washington 98119, USA. rfoti@amgen.com
Herbal-based remedies are widely used as alternative treatments for a number of ailments. In addition, the use of products that contain both single and multiple herbal constituents is becoming increasingly common. The work described in this report examined the in vitro drug interaction potential for a commonly used herbal cold remedy reported to contain a mixture of eight herbal components. Experiments conducted in human liver microsomes exhibited significant inhibition (<10% of control activity remaining) of multiple cytochrome P450 (P450) isoforms, including CYP2B6, CYP2C9, and CYP2D6, by the herbal mixture. In an attempt to explain the observed P450 inhibition by the herbal mixture, individual active components were obtained and tested for inhibitory potency. Inhibition of multiple P450 activities by a single constituent, luteolin, was observed. Conversely, inhibition of a single isoform by several herbal components was noted for CYP2B6. Based on the data presented, it is concluded that mixtures of herbal components may exhibit multiple modes of P450 inhibition, indicating the potential for complex herbal-drug interaction scenarios to occur.
PMID: 17093003

Finally, they claim that luteolin is a more powerful inhibitor of sulphation than quercetin (and that's really saying something!) but according to the following, luteolin is not only not an inhibitor of sulphation, but it actually enhances glucuronidation 3-5 fold! That does not seem like what you want. Maybe resveratrol is a special case? I don't know what's up here.

Drug Metab Dispos. 2002 May;30(5):564-9. 
Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements.
Walle UK, Walle T.
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Recent studies in our laboratory in the human hepatic and intestinal cell lines Hep G2 and Caco-2 have demonstrated induction of UGT1A1 by the flavonoid chrysin (5,7-dihydroxyflavone) using catalytic activity assays and Western and Northern blotting. In the present study, we examined which features of the flavonoid structures were associated with induction of UGT1A1 and whether common drug-metabolizing enzyme inducers also produce this induction. We also determined whether flavonoid treatment affected sulfate conjugation and CYP1A1 activity. We used intact Hep G2 cells for these studies, with chrysin as the model substrate. Both glucuronidation and sulfation were measured. Hep G2 cells were pretreated for 3 days with 25 microM concentrations of 22 flavonoids (n = 4-12). Only four flavonoids demonstrated induction of glucuronidation similar to that of chrysin (i.e., 3-5-fold in the intact cells). These were acacetin, apigenin, luteolin, and diosmetin, all of which, like chrysin, are 5,7-dihydroxyflavones with varying substituents in the B-ring. 5-Hydroxy-7-methoxyflavone and 5-methyl-7-hydroxyflavone produced a modest 1.5 to 2-fold induction, whereas all other flavonoids examined were without effect. None of the flavonoids caused more than a modest change in sulfation activity (60-140% of control). In contrast, all tested 5,7-dihydroxyflavones and -flavonols induced CYP1A1 activity (ethoxyresorufin deethylation). Of seven common drug-metabolizing enzyme inducers only 3-methylcholanthrene and oltipraz showed modest induction of chrysin glucuronidation but not 2,3,7,8-tetrachlorodibenzo-p-dioxin or phenobarbital. Together, these results strongly suggest that the flavonoid induction of UGT1A1 is through a novel nonaryl hydrocarbon receptor-mediated mechanism.
PMID: 11950788

Piperine: This may be another pGp efflux pump inhibitor. (PMID: 16243320) It may alter gut permeability resulting in increased absorption of some drugs (PMID: 12046863). I don't consider either of these putative activities to be particularly relevant. However, it appears to be an inhibitor of glucuronidation, and this may well be useful. In rats, it inhibited glucuronidation of EGCG in the gut by 40%, but did nothing in liver cells. See below and also PMID: 8347144.

J Nutr. 2004 Aug;134(8):1948-52.  Links
Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in mice.Lambert JD, Hong J, Kim DH, Mishin VM, Yang CS.
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey, Piscataway, NJ 08854, USA. joshua_lambert@hotmail.com

(-)-Epigallocatechin-3-gallate (EGCG), from green tea (Camellia sinensis), has demonstrated chemopreventive activity in animal models of carcinogenesis. Previously, we reported the bioavailability of EGCG in rats (1.6%) and mice (26.5%). Here, we report that cotreatment with a second dietary component, piperine (from black pepper), enhanced the bioavailability of EGCG in mice. Intragastric coadministration of 163.8 micromol/kg EGCG and 70.2 micromol/kg piperine to male CF-1 mice increased the plasma C(max) and area under the curve (AUC) by 1.3-fold compared to mice treated with EGCG only. Piperine appeared to increase EGCG bioavailability by inhibiting glucuronidation and gastrointestinal transit. Piperine (100 micromol/L) inhibited EGCG glucuronidation in mouse small intestine (by 40%) but not in hepatic microsomes. Piperine (20 micromol/L) also inhibited production of EGCG-3"-glucuronide in human HT-29 colon adenocarcinoma cells. Small intestinal EGCG levels in CF-1 mice following treatment with EGCG alone had a C(max) = 37.50 +/- 22.50 nmol/g at 60 min that then decreased to 5.14 +/- 1.65 nmol/g at 90 min; however, cotreatment with piperine resulted in a C(max) = 31.60 +/- 15.08 nmol/g at 90 min, and levels were maintained above 20 nmol/g until 180 min. This resulted in a significant increase in the small intestine EGCG AUC (4621.80 +/- 1958.72 vs. 1686.50 +/- 757.07 (nmol/g.min)). EGCG appearance in the colon and the feces of piperine-cotreated mice was slower than in mice treated with EGCG alone. The present study demonstrates the modulation of the EGCG bioavailablity by a second dietary component and illustrates a mechanism for interactions between dietary chemicals.

PMID: 15284381

From my brief consideration of this, it looks like quercetin should help resveratrol bioavailability, perhaps a fair amount. Luteolin appears as though it should hurt more than help, and piperine looks like it might help some, but I'm not sure how much. What is needed here is for someone to give these compounds to human volunteers along with some resveratrol, stick a needle in their arm and quantitate things. I have a strong suspicion that that has not yet happened, unless maybe Sirtris did it, but they probably aren't talking. I'd like to hear more from AOR.

Why not email them with the content of your post here?

Assuming that it is a good strategy to include quercetin with resveratrol, how is the "correct" amount of quercetin determined? If one takes 500 mg of resveratrol using AOR caps, the quercetin dose would be 5 times the dose for a person taking 100 mg. Does that make sense? Is there a reason for the quercetin dose to vary proportionally to the resveratrol dose?

Assuming that it is a good strategy to include quercetin with resveratrol, how is the "correct" amount of quercetin determined?  If one takes 500 mg of resveratrol using AOR caps, the quercetin dose would be 5 times the dose for a person taking 100 mg.  Does that make sense?  Is there a reason for the quercetin dose to vary proportionally to the resveratrol dose?

I suspect that they are assuming you are taking about 3 capsules. In fact, the label suggests 3 capsules/day.

The guys at Ergopharm agree with AOR on the use of piperine with resveratrol. Their new AI formula:

http://ergopharm.net...6oxoextreme.php

From what I have read, AOR seem to use ingredients that are the cutting edge of the science. This is not to say that these substances/compounds are well documented. I critiqued there new AOR advanced whey recently on my blog and here a while back and they included a compound that they believe to be unique and the next best thing since sliced bread. The report was based on information gained at a conference.

So from what I have read, AOR attempt to stay ahead of the rest by providing well studied compounds with a few added unique compounds that no other companies have included as yet. PQQ is a good example of this.

So what's ths special AOR whey compound?

Thanks!

Zoolander's blog post: http://www.health-hacker.com/?p=8

Assuming that it is a good strategy to include quercetin with resveratrol, how is the "correct" amount of quercetin determined? If one takes 500 mg of resveratrol using AOR caps, the quercetin dose would be 5 times the dose for a person taking 100 mg. Does that make sense? Is there a reason for the quercetin dose to vary proportionally to the resveratrol dose?

I can think of one reason.. Quercetin is extensively bound by serum albumin, so the vast majority of it is going to be taken out of play over a short time. By putting the quercetin in every pill, it's more likely that the quercetin will hit the liver in the first pass along with the resveratrol, and inhibit sulfation before it is pulled out of free circulation, and perhaps more importantly, be available for inhibition of sulfation in the gut. If you take multiple capsules at one time, then you might get more quercetin than you "need", but it probably would not constitute a grossly excessive amount unless you are taking large doses of resveratrol. And therein lies the problem with an approach like this: Do you want to be messing with efflux pumps, intestinal transit time, various P450s, all of which could affect the dose you are getting of other drugs or exogenous toxins? If you stay within the recommended dose, you will probably not have a problem, but I would be astounded if you could get a package like this past the FDA, and there is no way in hell it would happen without actual pharmacokinetic testing in humans.

nice one Shep.

I think the unique compound in AOR advanced whey is ......

I think the unique compound in AOR advanced whey is ......

Air?

AOR's resveratrol formulation

Where can i buy it?

Canada http://www.cureself....ROD&ProdID=4551

Price comparisons:

Brand----------mg of t-Resveratrol per US dollar
Longevinex......................108.25
Ray & Terry's..................131.69
AOR Acta-resveratrol......216.52

AOR gives you twice the trans-resveratrol per dollar than Longevinex. Part of that savings comes from the good price at feelgreatgetfit.com.

By the way, I emailed iherb and asked for them to carry AOR. Hope they listen!

Stephen

Still rather spendy, these low dose formulations, as compared to some other options.

CURESELF sells the 6-pack for C$224 or 20% less than the GET FIT site.

Thoughts on NOW's Natural Resveratrol? Price that out.

http://www.bodybuild...ore/now/nr.html

60 caps and 50mg of trans-resveratrol per cap. Plus Red Wine Extract, Green Tea Extract, and Grapeseed Extract.

NOW's Tru-E (high gamma-E, broken down for tocopherols and tocotrienols) and Tru-C products are exciting to me as well...superceding that of the AOR's and LEF's. http://www.bodybuild...ow/truebio.html

NOW, AFAIK, makes good stuff; however, this is relatively more expensive than similar resveratrol + other stuff supplements provided by Country Life and Doctor's Best, as well as pure resveratrol supplements provided by RevGenetics and Bioforte.

See Anthony Loera's beautiful price comparision site: Resveratrol Pricing Comparison
Edited by tintinet, 21 April 2007 - 12:56 AM.

NOW, AFAIK, makes good stuff; however, this is relatively more expensive than similar resveratrol + other stuff supplements provided by Country Life and Doctor's Best, as well as pure resveratrol supplements provided by RevGenetics and Bioforte.

See Anthony Lowera's beautiful price comparision site:  Resveratrol Pricing Comparison

That is a nice chart, but it shows that NOW is by far and away the best value. Their quality control and testing really is second to none. Even over the elite boutique types. I like the formulation of that product and again I use there Tru-E, Tru-C, and co-factor B complex that has methylcobablamin, and other goodies. For price and quality it seems hard to compete with them or Jarrow.

NOW, AFAIK, makes good stuff; however, this is relatively more expensive than similar resveratrol + other stuff supplements provided by Country Life and Doctor's Best, as well as pure resveratrol supplements provided by RevGenetics and Bioforte.

See Anthony Lowera's beautiful price comparision site:  Resveratrol Pricing Comparison

That is a nice chart, but it shows that NOW is by far and away the best value. Their quality control and testing really is second to none. Even over the elite boutique types. I like the formulation of that product and again I use there Tru-E, Tru-C, and co-factor B complex that has methylcobablamin, and other goodies. For price and quality it seems hard to compete with them or Jarrow.

and 2 + 2 = 5.

(IMHO)

CURESELF sells the 6-pack for C$224 or 20% less than the GET FIT site.

If Cureself will sell Acta Resveratrol for Can$ 224 - I'm interested. Checking their site - I can't seem to
get the cost under $307 ? (for 6)
Could I get a direct link or PM? tx

Welcome Guest! | My Account | My Favorites | History | Contact Us, Help | Letters | Username: Password:

Advanced Search
Your Shopping Cart
Product Price Quantity Total

AOR Acta Resveratrol - 90 vegi caps
C$53.98
C$323.88

Subtotal C$323.88

Discounts -C$16.19

Total
(excluding tax) C$307.69

6 Items In Your Cart[COLOR=gray]

YOU'RE CORRECT! THEY RAISED THE PRICE BY 37% DURING THE PAST WEEK?

I PURCHASED IT 0N 4-12 FOR THE PRICE OF C$224 FOR 6 AS SHOWN BELOW. i HAVE SINCE RECEIVED THE 6 BOTTLES.

Your Shopping Cart
Product Description Price
Quantity
Total

AOR Acta Resveratrol - 90 vegi caps
C$39.26
6 C$235.56

Product Total C$235.56
Shipping & Handling C$0.00

Sub Total C$235.56

Discounts -C$11.78

Final Total C$223.78

NOW, AFAIK, makes good stuff; however, this is relatively more expensive than similar resveratrol + other stuff supplements provided by Country Life and Doctor's Best, as well as pure resveratrol supplements provided by RevGenetics and Bioforte.

See Anthony Lowera's beautiful price comparision site:  Resveratrol Pricing Comparison

That is a nice chart, but it shows that NOW is by far and away the best value. Their quality control and testing really is second to none. Even over the elite boutique types. I like the formulation of that product and again I use there Tru-E, Tru-C, and co-factor B complex that has methylcobablamin, and other goodies. For price and quality it seems hard to compete with them or Jarrow.

and 2 + 2 = 5.

(IMHO)

What is it you meant by this. I didn't catch whether it was serious, sarcastic or what it was implying in regards to the statements above. I know there is synergy assumed by the math, but I was fuzzy as to what it was in regards to.

Maybe the Trans-resveratrol, Red Wine Extract, Green Tea Extract, and Grapeseed all in a natural, extremely reasonably priced product. $12 is better than $70 to me.

I actually do take NOW's Quercetin as well (it also has bromelain), so this thread was interesting to me. AOR and Geronova are two favorites of mine for quality. LEF often disappoints with headscratching formulations, that are inexcusable with their resources and position in the industry. NSI is a nice company from vitacost. Good prices. Looking at some of those companies mentioned in the chart.

AOR resveratrol has titanium:

"Some scientists are concerned about the extremely 'sticky' nature of Ti O2; it may very well adhere to the walls of blood vessels and thus contribute to coronary heart disease. It is advisable to avoid the ingestion of titanium dioxide. All health products containing potentially dangerous additives should be recalled immediately." Dr. E.K. Schandl:

http://www.caprofile...IDEwarning.html

"Titanium dioxide, a compound whose toxicity remains unclear, is an ingredient found in many sunscreens. Researchers now say the chemical can be absorbed by human skin. Titanium dioxide is a fine, white powder, used in sunscreens because of its ability to reflect and scatter ultraviolet light. The compound's full effects on human health are still under investigation. The U.S. government's National Institute for Occupational Safety and Health (NIOSH) labels the chemical "a potential occupational carcinogen."
[Skin & Allergy News February 1997, p. 15]:

http://www.mercola.c..._sunscreens.htm

You mind as well buy Longevinex which also has titanium and half the price with Pfizer quality behind it.

Pfizer doesn't allow supplement companies to use their LiCaps. Pfizer actually does it. So, whenever a supplement is using LiCaps you can be rest assured of good quality. Pfizer is the world's largest pharmaceutical company.

I don't think NOW's resveratrol is as cheap as Country Life's per mg. Country Life is twice the dose per Vcap at 100mg.

Plus, NOW resveratrol has Green tea which inhibits SIRT1 which acts counterproductive.

You can drink organic green tea. But, I'd steer clear of green tea supplements
Edited by mirian, 18 June 2007 - 04:14 AM.