ORAL Resveratrol - Destroyed in the Gut???

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    ORAL Resveratrol - Destroyed in the Gut???


    I've been on NP's for awhile. Before that, I was on T-Rez caps. 7+ months. HIGH doses so $$$$ because of all the profound benefits.

    I just want to make sure I'm actually getting something out of it. Unfortunately, I've been reading enough reports refuting all benefits of oral resveratrol that I am doubtful I'm geting much if anything. This is not a bash on NP or anyone else selling Resveratrol. I am merely trying to gain insight as to if this stuff is actually efficacious/bioavailable upon ORAL consumption.

    Please provide studies. Thanks

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    "In six healthy volunteers, Dr. Walle and colleagues examined the absorption and bioavailability of radiolabeled resveratrol after oral and intravenous administration of the antioxidant in doses roughly matching normal dietary intake.

    They found that after oral dosing, most of the resveratrol showed up in urine in the first 12 hours, and it appeared only as sulfate and glucuronic acid conjugates. The free, presumably active form of resveratrol was not present in urine or blood samples after oral dosing. Similarly, after intravenous injection, free resveratrol was only detected in blood samples drawn 30 minutes after injection.

    "We found no evidence that any resveratrol will reach into the systemic circulation," Dr. Walle told Reuters Health, "and the reason for that is very extensive metabolism of resveratrol as it is being absorbed into the body. It is completely broken down into metabolites very rapidly."

    Dr. Walle knows of one other study involving four individuals that supports his findings that "very low if any" amounts of active resveratrol will reach the circulation in humans."

    http://www.oncolink.org/resources/ar...h=04&year=2004

    Here is the link to the original study:

    http://dmd.aspetjournals.org/cgi/con...act/32/12/1377

    And the abstract for those who want it:

    HIGH ABSORPTION BUT VERY LOW BIOAVAILABILITY OF ORAL RESVERATROL IN HUMANS

    Thomas Walle, Faye Hsieh, Mark H. DeLegge, John E. Oatis, Jr., and U. Kristina Walle

    Department of Cell and Molecular Pharmacology and Experimental Therapeutics (T.W., J.E.O., U.K.W.) and Digestive Disease Center (M.H.D.), Medical University of South Carolina, Charleston, South Carolina; and Amgen, Inc., Thousand Oaks, California (F.H.)


    The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability, and metabolism of 14C-resveratrol after oral and i.v. doses in six human volunteers. The absorption of a dietary relevant 25-mg oral dose was at least 70%, with peak plasma levels of resveratrol and metabolites of 491 ▒ 90 ng/ml (about 2 ÁM) and a plasma half-life of 9.2 ▒ 0.6 h. However, only trace amounts of unchanged resveratrol (<5 ng/ml) could be detected in plasma. Most of the oral dose was recovered in urine, and liquid chromatography/mass spectrometry analysis identified three metabolic pathways, i.e., sulfate and glucuronic acid conjugation of the phenolic groups and, interestingly, hydrogenation of the aliphatic double bond, the latter likely produced by the intestinal microflora. Extremely rapid sulfate conjugation by the intestine/liver appears to be the rate-limiting step in resveratrol's bioavailability. Although the systemic bioavailability of resveratrol is very low, accumulation of resveratrol in epithelial cells along the aerodigestive tract and potentially active resveratrol metabolites may still produce cancer-preventive and other effects.
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    I don't know about it's absorption potential, but T-Rez works great for me. I take it on an empty stomach. I have similar results/feelings when I use Sustain Alpha.
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    Quote Originally Posted by bioman View Post
    I don't know about it's absorption potential, but T-Rez works great for me. I take it on an empty stomach. I have similar results/feelings when I use Sustain Alpha.
    god to know bud!
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    People who have blood work after using it have higher T and lower E, so it must do something...I will be making my first run with it very soon
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    The stomach wont destroy resveratrol. The problem is really dissolution and solubility of res through the GI.

    The Walle, et al study dissolved the resveratrol in an ethanol, DMSO, glucose solution and that had good oral absorption, but thats different than tablets and capsules that need to get disintergrated and molecularily dispersed.

    Liqua-Vade solves these problems, you could also try to blend your res powder into a glass of wine, a shake or something to help it disperse and dissolve.

    -Eric
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    Quote Originally Posted by Primordial Perf View Post
    The stomach wont destroy resveratrol. The problem is really dissolution and solubility of res through the GI.

    The Walle, et al study dissolved the resveratrol in an ethanol, DMSO, glucose solution and that had good oral absorption, but thats different than tablets and capsules that need to get disintergrated and molecularily dispersed.

    Liqua-Vade solves these problems, you could also try to blend your res powder into a glass of wine, a shake or something to help it disperse and dissolve.

    -Eric
    When I was taking bulk resveratrol I misxed in grapefruit juice with a dash of black pepper.
    Worked pretty well.

    Very interested in trying the Primordial Liqua-Vade Sustain pretty soon as well.
    "I don't want anything. I don't want anybody. That's the worst part. When the want goes, that's bad."
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    Quote Originally Posted by Primordial Perf View Post
    The stomach wont destroy resveratrol. The problem is really dissolution and solubility of res through the GI.

    The Walle, et al study dissolved the resveratrol in an ethanol, DMSO, glucose solution and that had good oral absorption, but thats different than tablets and capsules that need to get disintergrated and molecularily dispersed.

    Liqua-Vade solves these problems, you could also try to blend your res powder into a glass of wine, a shake or something to help it disperse and dissolve.

    -Eric

    i read this somewhere :

    ''Alcoholic beverages are a good delivery vehicle for resveratrol because resveratrol is highly soluble in ethyl alcohol (ethanol). By contrast, resveratrol is nearly insoluble in water. This makes an alcoholic beverage a very good delivery vehicle for resveratrol. Mixing resveratrol with alcoholic beverages will facilitate consumption of the amounts of resveratrol necessary to achieve the desired health benefits.''

    so im thinking a good transport would be to take a shot of peppermint schnapps, a cup of grapefruit juice ( for the naringin), and open up my capsule of t rez, and blend it, and take it twice a day.
    For me, the action IS the juice.
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    Quote Originally Posted by soontobbeast View Post
    i read this somewhere :

    ''Alcoholic beverages are a good delivery vehicle for resveratrol because resveratrol is highly soluble in ethyl alcohol (ethanol). By contrast, resveratrol is nearly insoluble in water. This makes an alcoholic beverage a very good delivery vehicle for resveratrol. Mixing resveratrol with alcoholic beverages will facilitate consumption of the amounts of resveratrol necessary to achieve the desired health benefits.''

    so im thinking a good transport would be to take a shot of peppermint schnapps, a cup of grapefruit juice ( for the naringin), and open up my capsule of t rez, and blend it, and take it twice a day.
    Yeah, that wouldn't be a bad idea...

    -Eric
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    Quote Originally Posted by bioman View Post
    I don't know about it's absorption potential, but T-Rez works great for me. I take it on an empty stomach. I have similar results/feelings when I use Sustain Alpha.

    Good to hear. You're one of the lucky ones

    http://www.ncbi.nlm.nih.gov/pubmed/15779070
    Metabolism and bioavailability of trans-resveratrol.
    Wenzel E, Somoza V.

    German Research Center of Food Chemistry, Garching, Germany. elisabeth.wenzel@lrz.tum.de

    Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a polyphenolic compound accounting to the stilbene class. Most stilbenes in plants act as antifungal phytoalexins, compounds that are usually synthesized only in response to infection or injury. Resveratrol has been detected in trees, in a few flowering plants, in peanuts, and in grapevines. The major dietary sources of resveratrol include grapes, wine, peanuts, and peanut products. Numerous in vitro studies describe different biological effects of resveratrol. The major impacts are the antioxidative, anti-inflammatory, and estrogenic effects as well as anticancer and chemopreventive activities. In order to reveal information on absorption, metabolism, and the consequent bioavailability of resveratrol, different research approaches were performed, including in vitro, ex vivo, and in vivo models, all of which are considered in this review. Summarizing the data, resveratrol is absorbed and metabolized. Around 75% of this polyphenol are excreted via feces and urine. The oral bioavailability of resveratrol is almost zero due to rapid and extensive metabolism and the consequent formation of various metabolites as resveratrol glucuronides and resveratrol sulfates. The potential biologic activity of resveratrol conjugates should be considered in future investigations.

    PMID: 15779070 [PubMed - indexed for MEDLINE]
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    http://dmd.aspetjournals.org/cgi/con...act/32/12/1377

    VERY LOW BIOAVAILABILITY OF ORAL RESVERATROL IN HUMANS
    Thomas Walle, Faye Hsieh, Mark H. DeLegge, John E. Oatis, Jr., and U. Kristina Walle
    Department of Cell and Molecular Pharmacology and Experimental Therapeutics (T.W., J.E.O., U.K.W.) and Digestive Disease Center (M.H.D.), Medical University of South Carolina, Charleston, South Carolina; and Amgen, Inc., Thousand Oaks, California (F.H.)


    The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability, and metabolism of 14C-resveratrol after oral and i.v. doses in six human volunteers. The absorption of a dietary relevant 25-mg oral dose was at least 70%, with peak plasma levels of resveratrol and metabolites of 491 ▒ 90 ng/ml (about 2 ÁM) and a plasma half-life of 9.2 ▒ 0.6 h. However, only trace amounts of unchanged resveratrol (<5 ng/ml) could be detected in plasma. Most of the oral dose was recovered in urine, and liquid chromatography/mass spectrometry analysis identified three metabolic pathways, i.e., sulfate and glucuronic acid conjugation of the phenolic groups and, interestingly, hydrogenation of the aliphatic double bond, the latter likely produced by the intestinal microflora. Extremely rapid sulfate conjugation by the intestine/liver appears to be the rate-limiting step in resveratrol's bioavailability. Although the systemic bioavailability of resveratrol is very low, accumulation of resveratrol in epithelial cells along the aerodigestive tract and potentially active resveratrol metabolites may still produce cancer-preventive and other effects.
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    Quote Originally Posted by Whacked View Post
    Good to hear. You're one of the lucky ones

    http://www.ncbi.nlm.nih.gov/pubmed/15779070
    Metabolism and bioavailability of trans-resveratrol.
    Wenzel E, Somoza V.

    German Research Center of Food Chemistry, Garching, Germany. elisabeth.wenzel@lrz.tum.de

    Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a polyphenolic compound accounting to the stilbene class. Most stilbenes in plants act as antifungal phytoalexins, compounds that are usually synthesized only in response to infection or injury. Resveratrol has been detected in trees, in a few flowering plants, in peanuts, and in grapevines. The major dietary sources of resveratrol include grapes, wine, peanuts, and peanut products. Numerous in vitro studies describe different biological effects of resveratrol. The major impacts are the antioxidative, anti-inflammatory, and estrogenic effects as well as anticancer and chemopreventive activities. In order to reveal information on absorption, metabolism, and the consequent bioavailability of resveratrol, different research approaches were performed, including in vitro, ex vivo, and in vivo models, all of which are considered in this review. Summarizing the data, resveratrol is absorbed and metabolized. Around 75% of this polyphenol are excreted via feces and urine. The oral bioavailability of resveratrol is almost zero due to rapid and extensive metabolism and the consequent formation of various metabolites as resveratrol glucuronides and resveratrol sulfates. The potential biologic activity of resveratrol conjugates should be considered in future investigations.

    PMID: 15779070 [PubMed - indexed for MEDLINE]
    The blood metabolizes resveratrol pretty quick, but it doesnt mean that the conjugates aren't doing the same thing resveratrol is doing. Research is showing they have the same properties, albeit slightly weaker.

    -Eric
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    http://www.myhealthfulworld.com/?q=c...althy-subjects

    New Resveratrol study shows low bioavailability in vivo (healthy subjects)
    Submitted by MyHealthfulWorld on Mon, 02/09/2009 - 19:45.
    Resveratrol
    Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers : This was a double-blind, randomised, placebo-controlled study to investigate the pharmacokinetics and safety of trans-resveratrol. In four groups of ten healthy adult subjects (five males and five females), two subjects were randomized to receive placebo and eight subjects to receive trans-resveratrol 25, 50, 100 or 150 mg, six times/day, for thirteen doses. Peak plasma concentrations of trans-resveratrol were reached at 0.8-1.5 h postdose. Following the 13th dose of trans-resveratrol 25, 50, 100 and 150 mg, mean peak plasma concentration (C(max)) was 3.89, 7.39, 23.1 and 63.8 ng/mL and mean area under the plasma concentration-time curve (AUC(0-tau)) was 3.1, 11.2, 33.0 and 78.9 ng.h/mL. Interindividual variability was high, with coefficients of variation >40%. Trans-resveratrol half-life was 1-3 h following single-doses and 2-5 h following repeated dosing. Trough (C(min)) concentrations were less, not double equals1 ng/mL following 25 and 50 mg, 3 ng/mL following 100 mg and < 10 ng/mL following 150 mg. Trans-resveratrol pharmacokinetics showed circadian variation. Adverse events were mild in severity and similar between all groups. In conclusion, repeated administration was well-tolerated but produced relatively low plasma concentrations of trans-resveratrol, despite the high doses and short dosing interval used.
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    i didn't read the studies, but were they using trans-res?
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    Isn't this why some formulas have Quercetin to inhibit sulfation of t-resv. by the liver?
    Source: Xenobiotica, Volume 30, Number 6, 1 June 2000, pp. 609-617(9)

    I alway keep mine t-resv. in the refigerator and take it with quercetin.
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    What about this?

    Thomas Walle and colleagues at the University of South Carolina confirm that a minimum of 70 percent of oral resveratrol, as a small molecule, is absorbed in the human digestive tract, but thereafter most resveratrol in blood plasma is conjugated with (complexed with) sulfur and glucuronic acid as it passes through the liver.[Drug Metabolism Disposition 32:1377–82, 2004]

    Pharm Res. 2006 Sep;23(9):2107-15. Epub 2006 Aug 9. Links
    Increased transport of resveratrol across monolayers of the human intestinal Caco-2 cells is mediated by inhibition and saturation of metabolites.
    ………….. PURPOSE: The study's aim was to investigate the dose-dependent effect of sulfation and glucuronidation on intestinal absorption of resveratrol, a dietary constituent found in grapes and various medical plants. MATERIALS AND METHODS: The intestinal epithelial membrane transport kinetics and metabolism of resveratrol (10-200 microM) was studied using Caco-2 monolayers cultured in Transwells.
    RESULTS: Along with resveratrol it was possible to identify three metabolites, namely, resveratrol-4'-O-glucuronide (M1), resveratrol 3-O-gucuronide (M2), and resveratrol-3-O-sulfate (M3) by LC/MS and NMR. Efflux of the glucuronides M1 and M2 followed Michaelis-Menten kinetics significantly favouring basolateral efflux. The predominant metabolite was the monosulfate M3, however, its formation was strongly inhibited at higher resveratrol concentrations. As biotransformation was either inhibited or saturated, total amount of resveratrol transported across the Caco-2 monolayers increased as much as 3.5-fold at 200 microM resveratrol. This value might be even higher when taking into account the high intracellular concentration of resveratrol, which accounted for up to 61% of the applied dose. CONCLUSIONS: Our data demonstrate a concentration-dependent biotransformation of resveratrol in Caco-2 cells, which may also apply to human enterocytes affecting oral bioavailability.
    PMID: 16952002

    Researchers at the Institute of Human Virology, University of Maryland Biotechnology Institute, have written an extensive report describing the biological aspects of liver metabolism and resveratrol. Here is an excerpt paraphrased from their paper:
    What is the biological function of glucuronidation of resveratrol in humans? What is the real bioactive form of resveratrol in living organisms? …There are examples showing that liver metabolism (glucuronidation) has a role in drug disposition and drug targeting in humans. It is known that beta-glucuronidase, the enzyme that breaks down glucuronide, is widely expressed in organs, tissues, and body fluids in humans. Therefore, this enzyme may release a drug or bound molecule like resveratrol locally or systemically from a glucuronide conjugate (such as resveratrol glucuronide). In fact, many glucuronide prodrugs have been designed and are under development that bind a synthetic drug molecule to glucuronide which subsequently depends upon the beta-glucuronidase enzyme to release it into living tissues.

    Therefore, it is likely that at least a portion of resveratrol is unzipped from its protective carrier by the glucuronidase enzyme and could be converted back to free resveratrol. Since tissue or serum beta-glucuronidase enzyme activity is elevated in certain diseased tissues, such as cancer, liver diseases, and AIDS, resveratrol would be targeted and released more so in these tissues than in healthy ones. Researchers state that “these observations… raise the possibility that glucuronidation of resveratrol may have a role in detoxification, disposition, and prolongation of the effectiveness of resveratrol in humans.” [Journal Pharm Science 93:2448–2457, 2004]
    Thanks to 1HP
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    when patrick arnold was introducing 6oxo extreme he was very clear that trans-res was what you wanted. i see no mention of trans-res being used in those studies.
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    don't forget reverse from ibe, according to them their stuff have a lot more bioavallity
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    Quote Originally Posted by nunes View Post
    don't forget reverse from ibe, according to them their stuff have a lot more bioavallity
    pp is introducing new delivery system, check it out. oral vida or something?
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    Quote Originally Posted by thebigt View Post
    pp is introducing new delivery system, check it out. oral vida or something?
    yeah, they say it works better than the transdermal
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    TRANS RESV

    Quote Originally Posted by Whacked View Post
    Good to hear. You're one of the lucky ones

    http://www.ncbi.nlm.nih.gov/pubmed/15779070
    Metabolism and bioavailability of trans-resveratrol.
    Wenzel E, Somoza V..

    PMID: 15779070 [PubMed - indexed for MEDLINE]
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    Quote Originally Posted by Primordial Perf View Post
    The stomach wont destroy resveratrol. The problem is really dissolution and solubility of res through the GI.

    The Walle, et al study dissolved the resveratrol in an ethanol, DMSO, glucose solution and that had good oral absorption, but thats different than tablets and capsules that need to get disintergrated and molecularily dispersed.

    Liqua-Vade solves these problems, you could also try to blend your res powder into a glass of wine, a shake or something to help it disperse and dissolve.

    -Eric
    So are you saying that we need alcohol, or just a blender to blend it up?
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    I was thinking about some Glenlivet scotch..lolz
    I would think the best alcohol to mix res with would be red wine....
    Just makes obvious sense.
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    Quote Originally Posted by kingdong View Post
    So are you saying that we need alcohol, or just a blender to blend it up?
    Yeah, you need a solvent... just water or juice wont really cut it.

    -Eric
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    doesnt the Piperine in t rez help absorption and are those studies on just plan resveratrol
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    hey Eric, ive just about finished my bottle of SA for my pct, without going off topic may I ask why you guys haven't used Quercetin in your formulation(s) with Resveratrol? Would you be able to kindly explain the advantages/disadvantages of this?
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    Quote Originally Posted by WilteredFire View Post
    hey Eric, ive just about finished my bottle of SA for my pct, without going off topic may I ask why you guys haven't used Quercetin in your formulation(s) with Resveratrol? Would you be able to kindly explain the advantages/disadvantages of this?
    The formula works well as it is. Introducing another flavone such as quercetin may inhibit/antagonize certain actions from the res/bzf so we just dont bother with it.

    -Eric
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