1708 replies to this topic

[rfarris]

I'm up to 600mg/day (300mg/AM, 300mg/PM) and as a diabetic, I check my glucose when I awake each day. Mine has been low lately -- high 80s or low 90s. I presumed it was related to the fact that I've been drinking a little more than usual, but I suppose it could have something to do with the t-res.

(BTW, is it really necessary to include complete quoting of previous messages? A short summary to remind someone which message you're referring to is helpful, but quoting several dozen lines to make a three-line comment seems, I dunno, wasteful...)

[sUper GeNius]

I'm up to 600mg/day (300mg/AM, 300mg/PM) and as a diabetic, I check my glucose when I awake each day.  Mine has been low lately -- high 80s or low 90s.  I presumed it was related to the fact that I've been drinking a little more than usual, but I suppose it could have something to do with the t-res.

(BTW, is it really necessary to include complete quoting of previous messages?  A short summary to remind someone which message you're referring to is helpful, but quoting several dozen lines to make a three-line comment seems, I dunno, wasteful...)

Ascii is cheap.

[sUper GeNius]

The "hunger" some people are associating with high dose T-Res might be because of the depressed blood sugar levels caused by T-Res.

That's what I suspect in my case. I had slightly elevated sugar to begin with prior to t-res.

[maxwatt]

I've not noted any decrease in fasting glucose.

Some CR guy did a presentation where he compared his glucose measured at quick intervals after a meal both control and after being on T-Res. The control glucose spiked after the meal, while the glucose levels when on T-Res were significantly depressed, being nearly close to fasting levels.
http://video.google....2&q=resveratrol

I can't find the full presentation but the first 10 seconds of it with one of his graphs is on the above link.

I've been told of studies showing r-res increases insulin sensitivity, but does not lower fasting glucose.

(edited to more precisely define blood sugar as fasting glucose)

Edited by maxwatt, 17 April 2007 - 05:51 PM.

[tintinet]

Hey tintinet

If you don't mind, could you post your current dosage and timing?
What else are you dosing your Res-v with?

I've been taking 500 mg of Country Life with a TBS of Fish Oil in the morning on an empty stomache
...Based on some of the posts i've seen this really doesn't seem ideal

I'm not sure anyone knows what "ideal" dosing of t-resv. might be, now.

Some advocate "swamping" the liver's capacity to metabolize and modify t-resv., while
other aver time spaced dosing over the course of the day is best. And then there's the
issue of absorption- with food or without, with lipids or alcohol or quercetin or biopterine...ad
infinitum (or so it at times seems.)

I take 1 Longevinex upon waking, no food, before AM workout. Then, depending upon mood,
enthusiasm for supplementation, etc. 250-500 mg with breakfast. Then, again, variable, 250-500 mg
with lunch, and again with dinner (also variable.)

I've ranged from about 250 mg day (long, long ago...) to current level of anywhere from 1-3 grams/day
(although usually more towards 1- did 3 for a bit just to see what it would be like.)

Maybe next I'll just take t-resv. with Pinot Noir all day long!

BTW, recently some have mentioned hunger as a side effect of t-resv.. For me, just the opposite. Very
appetite suppresive, IME.

[niner]

Some advocate "swamping" the liver's capacity to metabolize and modify t-resv., while
other aver time spaced dosing over the course of the day is best. And then there's the
issue of absorption- with food or without, with lipids or alcohol or quercetin or biopterine...ad
infinitum (or so it at times seems.)

I don't know about swamping the liver; my sense is that at these dosages that's not likely, but in the gut it's another story. The following paper was done using Caco-2 cells, a commonly used standin for the gut. It's an in-vitro system, but a pretty good model, as the gut metabolic enzymes are there. They see a 3.5 fold increase in transport at 200 microM, suggesting that the gut may well be swampable. Since it's a site of significant resveratrol conjugation, this may help. The "swamping effect" should be enhanced by taking resveratrol on an empty stomach. I've seen no evidence that any particular food or solvent makes much difference with resveratrol. Quercetin "should" help, but I'm having a hard time coming up with any solid in vivo data. I emailed Bill Sardi and asked him if he knew of any resveratrol/quercetin pharmacokinetic experiments in humans. He got right back to me, but no human data. My intuition would be to take the quercetin at the same time as the resveratrol, but I did find one paper which found that pre-treatment of rats with quercetin for 3 days resulted in levels of oral paclitaxel, the drug they were looking at, that were "much higher" than when it was taken 20 minutes after the quercetin. Different drug, different species, but it's consistent with quercetin's long half life. I still worry about the high affinity that quercetin has for serum albumin; my concern is that the albumin is going to bind it all and prevent it from engaging in persistent sulfotransferase inhibition, but maybe I'm wrong. That's why I'd really like to see some human data for the combination. The paclitaxel paper is below.

Pharm Res. 2006 Sep;23(9):2107-15. Epub 2006 Aug 9.
Increased transport of resveratrol across monolayers of the human intestinal Caco-2 cells is mediated by inhibition and saturation of metabolites.
Maier-Salamon A, Hagenauer B, Wirth M, Gabor F, Szekeres T, Jager W.
Department of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090, Vienna, Austria.
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

Eur J Pharm Biopharm. 2004 Mar;57(2):313-8.
Enhanced paclitaxel bioavailability after oral administration of paclitaxel or prodrug to rats pretreated with quercetin.
Choi JS, Jo BW, Kim YC.
College of Pharmacy, Chosun University, Gwangju, South Korea. jsachoi@chosun.ac.kr
The aim of this study was to investigate the effect of quercetin on the bioavailability of paclitaxel after the oral administration of paclitaxel or a prodrug to rats pretreated with quercetin. Paclitaxel (40 mg/kg) and prodrug (280 mg/kg, 40 mg/kg as the paclitaxel) were administered orally to rats pretreated with quercetin (2, 10, 20 mg/kg). The plasma concentrations of paclitaxel pretreated with quercetin were increased significantly (P < 0.01 for paclitaxel; P < 0.05 for prodrug) compared to the control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations (Cmax) of paclitaxel pretreated with quercetin were significantly higher (P < 0.01) than the control. The half-life (t(1/2)) and mean residence times were significantly (P < 0.05) longer compared to the control. The absolute bioavailability (AB%) of paclitaxel pretreated with quercetin was significantly higher (P < 0.01) than the control. The AUC of paclitaxel after administration of the prodrug to rats pretreated with quercetin was significantly (P < 0.05) higher than the prodrug control. The relative bioavailability of paclitaxel after administration of the prodrug to rats pretreated with quercetin was 1.25- to 2.02-fold higher than the prodrug control. The AB% of paclitaxel was increased significantly (P < 0.05) by quercetin from 8.0 to 10.1 and 16.2%. The bioavailability of paclitaxel administered as a prodrug with or without pretreatment of quercetin was remarkably higher than the control. AUC, AB% and Cmax of paclitaxel after administration of the paclitaxel or prodrug pretreated with quercetin for 3 days were much higher than those administered after 20 min. It might have resulted from the physicochemical properties of the prodrug, which is a water-soluble compound and passes through the gastrointestinal mucosa more easily than paclitaxel without obstruction of P-gp and cytochrome P-450 in the gastrointestinal mucosa. It seems that the development of oral paclitaxel preparations as a prodrug or with quercetin is feasible, which is more convenient than the i.v. dosage forms.
PMID: 15018990

[bixbyte]

*********************************************************************
In order for this RSV absorption data to be validated, I Think,
You would need a very short human study of min two groups

1. pretreat Quercin, then RSV
2. RSV on empty stomach

(maybe a third or forth test group say omega 3 ...)


U/A and Blood tests on each group

Alex

************************************************

Some advocate "swamping" the liver's capacity to metabolize and modify t-resv., while
other aver time spaced dosing over the course of the day is best. And then there's the
issue of absorption- with food or without, with lipids or alcohol or quercetin or biopterine...ad
infinitum (or so it at times seems.)

I don't know about swamping the liver; my sense is that at these dosages that's not likely, but in the gut it's another story. The following paper was done using Caco-2 cells, a commonly used standin for the gut. It's an in-vitro system, but a pretty good model, as the gut metabolic enzymes are there. They see a 3.5 fold increase in transport at 200 microM, suggesting that the gut may well be swampable. Since it's a site of significant resveratrol conjugation, this may help. The "swamping effect" should be enhanced by taking resveratrol on an empty stomach. I've seen no evidence that any particular food or solvent makes much difference with resveratrol. Quercetin "should" help, but I'm having a hard time coming up with any solid in vivo data. I emailed Bill Sardi and asked him if he knew of any resveratrol/quercetin pharmacokinetic experiments in humans. He got right back to me, but no human data. My intuition would be to take the quercetin at the same time as the resveratrol, but I did find one paper which found that pre-treatment of rats with quercetin for 3 days resulted in levels of oral paclitaxel, the drug they were looking at, that were "much higher" than when it was taken 20 minutes after the quercetin. Different drug, different species, but it's consistent with quercetin's long half life. I still worry about the high affinity that quercetin has for serum albumin; my concern is that the albumin is going to bind it all and prevent it from engaging in persistent sulfotransferase inhibition, but maybe I'm wrong. That's why I'd really like to see some human data for the combination. The paclitaxel paper is below.

Pharm Res. 2006 Sep;23(9):2107-15. Epub 2006 Aug 9.
Increased transport of resveratrol across monolayers of the human intestinal Caco-2 cells is mediated by inhibition and saturation of metabolites.
Maier-Salamon A, Hagenauer B, Wirth M, Gabor F, Szekeres T, Jager W.
Department of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090, Vienna, Austria.
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

Eur J Pharm Biopharm. 2004 Mar;57(2):313-8.
Enhanced paclitaxel bioavailability after oral administration of paclitaxel or prodrug to rats pretreated with quercetin.
Choi JS, Jo BW, Kim YC.
College of Pharmacy, Chosun University, Gwangju, South Korea. jsachoi@chosun.ac.kr
The aim of this study was to investigate the effect of quercetin on the bioavailability of paclitaxel after the oral administration of paclitaxel or a prodrug to rats pretreated with quercetin. Paclitaxel (40 mg/kg) and prodrug (280 mg/kg, 40 mg/kg as the paclitaxel) were administered orally to rats pretreated with quercetin (2, 10, 20 mg/kg). The plasma concentrations of paclitaxel pretreated with quercetin were increased significantly (P < 0.01 for paclitaxel; P < 0.05 for prodrug) compared to the control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations (Cmax) of paclitaxel pretreated with quercetin were significantly higher (P < 0.01) than the control. The half-life (t(1/2)) and mean residence times were significantly (P < 0.05) longer compared to the control. The absolute bioavailability (AB%) of paclitaxel pretreated with quercetin was significantly higher (P < 0.01) than the control. The AUC of paclitaxel after administration of the prodrug to rats pretreated with quercetin was significantly (P < 0.05) higher than the prodrug control. The relative bioavailability of paclitaxel after administration of the prodrug to rats pretreated with quercetin was 1.25- to 2.02-fold higher than the prodrug control. The AB% of paclitaxel was increased significantly (P < 0.05) by quercetin from 8.0 to 10.1 and 16.2%. The bioavailability of paclitaxel administered as a prodrug with or without pretreatment of quercetin was remarkably higher than the control. AUC, AB% and Cmax of paclitaxel after administration of the paclitaxel or prodrug pretreated with quercetin for 3 days were much higher than those administered after 20 min. It might have resulted from the physicochemical properties of the prodrug, which is a water-soluble compound and passes through the gastrointestinal mucosa more easily than paclitaxel without obstruction of P-gp and cytochrome P-450 in the gastrointestinal mucosa. It seems that the development of oral paclitaxel preparations as a prodrug or with quercetin is feasible, which is more convenient than the i.v. dosage forms.
PMID: 15018990

[fearfrost]

niner, what is the half-life of quercetin in humans? thanks in advance

[tintinet]

Damn good question: the studies I've seen range all over the map, from 1.5 hours to 16 hours....

[bixbyte]

Safety Issues
Quercetin appears to be quite safe. However, concerns have been raised that under some circumstances it might raise cancer risk. Quercetin "fails" a standard laboratory test called the Ames test, which is designed to identify chemicals that might be carcinogenic. Nonetheless, a bad showing on the Ames test does not definitely mean a chemical causes cancer. Most other evidence suggests that quercetin does not cause cancer, and may in fact help prevent cancer.19,20,21 Still, one highly preliminary study suggests that quercetin combined with other bioflavonoids in the diet of pregnant women might increase the risk of infant leukemia.22 On this basis, pregnant women should probably avoid quercetin supplements. Maximum safe dosages for young children, nursing women, or people with serious liver or kidney disease have not been established.

Evidence suggests that use of quercetin supplements can elevate urine and blood levels of the substance homovanillic acid.23 While this itself should be harmless, lab tests for homovanillic acid are used to diagnose a rare, dangerous condition called neuroblastoma, and for this reason use of quercetin supplements could potentially cause a false positive diagnosis of this condition.

[tintinet]

Yo bixbye: where did you get that info? Citation?

Thanks!

[trance]

Yo bixbye: where did you get that info? Citation?

Thanks!

He most likely got it from here:

http://healthlibrary...&chunkiid=21847

[bixbyte]

Yo bixbye: where did you get that info? Citation?

Thanks!

I am afraid of Quercetin unless I see a human double blind study
so I take my RSV with Fish Oil

cited: consumerlab.com

indie supplement lab tests for a low fee

[niner]

what is the half-life of quercetin in humans?

Damn good question: the studies I've seen range all over the map, from 1.5 hours to 16 hours....

There's a good review of flavonoids by Claudine Mannach at http://www.ajcn.org/.../full/81/1/230S that has elimination half times of quercetin from a number of studies, looking at different glycosides and plant matrices. Eight variations of glycoside or matrix, from five papers out of two labs, range from 15 to 28 hours. Some of the same variants, from a third lab, ranged from 10.3 to 11.9 hours. The only measurements on pure quercetin aglycone, all at the same lab, ranged from 15 to 18 hours. The source of the short half times that tintinet recalled might have been from people without intact colons. (One of the upsides of a colostomy is that you may become popular with pharmacokineticists.) Flavonoids get some of their long half times from enterohepatic recycling. They get conjugated in the liver, excreted in bile, then gut microflora cleave the conjugates whereupon they get reabsorbed. Without a colon, this mechanism is eliminated.

[fearfrost]

Wow, thanks a lot for that link niner. I wonder what I am doing to my body by taking 500 mg twice daily. Gees. That is a long time for that to stay in my body.

[sUper GeNius]

I just moved up to 800mg tres daily, and I intend to stay there until I have bloodwork done in two months time.

I am hedging my bets by using the following regimen.

In the morning, along with my Omega 3's, taking 100mg AOR in the morning along with 300mg another brand, currently NSI 100mg caps, probably will move to another brand that has 98% tres.


In the evening, duplicate the morning dose.

800mg total/day.


I do believe that there is a problem with bioavailability of straight t-res in humans, hence the addition of AOR, which also contains quercitin and Luteolin. OTOH, I do not want to take TOO much quercitin.

[maxwatt]

.....
I do believe that there is a problem with bioavailability of straight t-res in humans, hence the addition of AOR, which also contains quercitin and Luteolin.  OTOH, I do not want to take TOO much quercitin.

Nobody knows the optimum amount of quercetin to use, if any.

[steelheader]

Is there any advantage to making one's dose of t-res more potent by adding quercetin to the mix rather than simply increasing the dose of t-res?

[health_nutty]

If you look at the flavanoid content of food, even foods considered rich in quercetin are in the 5mg per 100g range.

1g a day of quercetin is a lot higher than even a diet with lots of quercetin rich foods will give you.

Here is the link where I got my quercetin info:

http://www.nal.usda....a/Flav/flav.pdf

Edited by health_nutty, 19 April 2007 - 07:35 PM.

[health_nutty]

J. Agric. Food Chem., 52 (4), 935 -942, 2004. 10.1021/jf030582e S0021-8561(03)00582-X
Web Release Date: January 23, 2004
Copyright © 2004 American Chemical Society

Urinary and Plasma Levels of Resveratrol and Quercetin in Humans, Mice, and Rats after Ingestion of Pure Compounds and Grape Juice

Xiaofeng Meng, Pius Maliakal, Hong Lu, Mao-Jung Lee, and Chung S. Yang*

Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, New Jersey 08854

Received for review August 7, 2003. Revised manuscript received December 3, 2003. Accepted December 5, 2003. This work was supported in part by the California Grape Commission (Fresno, CA).

Abstract:

The present study investigates the bioavailability of resveratrol and quercetin in humans, mice, and rats after oral ingestion of grape juice preparations or pure aglycones. Oral administration of resveratrol and quercetin to humans yielded detectable levels of resveratrol, quercetin, and their derivatives in the plasma and urine. Urinary levels of resveratrol, quercetin, and their metabolites were observed in human subjects receiving 600 and 1200 mL of grape juice, whereas quercetin metabolites were identified in urine samples even after receiving 200 mL of grape juice. The cumulative amounts of resveratrol and quercetin excreted in the urine of mice receiving concentrated grape juice for 4 days were 2.3 and 0.7% of the ingested doses, respectively. After i.g. administration of resveratrol to rats (2 mg/kg), up to 1.2 M resveratrol was observed in the plasma. The study demonstrates that the glycoside forms of resveratrol and quercetin in grape juice are absorbed to a lesser extent than the aglycones.

Keywords: Resveratrol; quercetin; grape juice; human; rodents; plasma; urine

[sUper GeNius]

.....
I do believe that there is a problem with bioavailability of straight t-res in humans, hence the addition of AOR, which also contains quercitin and Luteolin.  OTOH, I do not want to take TOO much quercitin.

Nobody knows the optimum amount of quercetin to use, if any.

Yep, no one knows. It's a gamble taking Q, and it's a gamble to not take it. My intuition tells me that t-res bioavailability is going to be a big issue in humans. I see alot more potential benefit from taking Q than potential negative effects from taking Q.

[sUper GeNius]

If you look at the flavanoid content of food, even foods considered rich in quercetin are in the 5mg per 100g range. 

1g a day of quercetin is a lot higher than even a diet with lots of quercetin rich foods will give you.

Here is the link where I got my quercetin info:

http://www.nal.usda....a/Flav/flav.pdf

That's why I intend to limit my intake to less than 200mg daily, until more info becomes available.

[niner]

I wonder what I am doing to my body by taking 500 mg twice daily. Gees. That is a long time for that to stay in my body.

You're probably raising your baseline levels, but based on Watjen et al. below, your peak levels are unlikely to be overtly dangerous. These guys looked at dietary flavonoids at different concentrations in assays for various good and bad activities of the compounds. As you might imagine, they were helpful at lower concentrations, but the undesirable effects start to predominate at higher concentration. In their in vitro cell-based assay, they saw protective effects at 10 microM, but saw damage beginning at 50 microM. They warn in the abstract that "Published data on quercetin pharmacokinetics in humans suggest that a dietary supplement of 1–2 g of quercetin may result in plasma concentrations between 10 and 50 µmol/L." However, at the end of the paper they tone it down a little, saying "...the data on quercetin pharmacokinetics in humans suggest that a dietary supplement of 1-2g of quercetin, an amount proposed by supplement makers, may result in plasma concentrations exceeding 10 microM, but probably not exceeding 50 microM if taken properly." I don't know what the minimum amount of quercetin would need to be in order to enhance bioavailability of resveratrol, but an argument can be made that taking your daily dose all at once would both encourage "swamping" of gut metabolism and also minimize quercetin use. This strategy may be less important at higher resveratrol dosages. (1+ gm)?

From: http://jn.nutrition....tract/135/3/525 (full text also available)
The American Society for Nutritional Sciences J. Nutr. 135:525-531, March 2005

Nutrient Interactions and Toxicity
Low Concentrations of Flavonoids Are Protective in Rat H4IIE Cells Whereas High Concentrations Cause DNA Damage and Apoptosis1,2
Wim Wätjen3, Gudrun Michels4, Bärbel Steffan*,4, Petra Niering4, Yvonni Chovolou, Andreas Kampkötter, Quynh-Hoa Tran-Thi, Peter Proksch* and Regine Kahl
Institute of Toxicology, Heinrich-Heine-University, 40001 Düsseldorf, Germany; and * Institute of Pharmaceutical Biology, Heinrich-Heine-University, 40225 Düsseldorf, Germany
3To whom correspondence should be addressed. E-mail: wim.waetjen@uni-duesseldorf.de
Dietary flavonoids possess a wide spectrum of biochemical and pharmacological actions and are assumed to protect human health. These actions, however, can be antagonistic, and some health claims are mutually exclusive. The antiapoptotic actions of flavonoids may protect against neurodegenerative diseases, whereas their proapoptotic actions could be used for cancer chemotherapy. This study was undertaken to determine whether a cytoprotective dose range of flavonoids could be differentiated from a cytotoxic dose range. Seven structurally related flavonoids were tested for their ability to protect H4IIE rat hepatoma cells against H2O2-induced damage on the one hand and to induce cellular damage on their own on the other hand. All flavonoids proved to be good antioxidants in a cell-free assay. However, their pharmacologic activity did not correlate with in vitro antioxidant potential but rather with cellular uptake. For quercetin and fisetin, which were readily taken up into the cells, protective effects against H2O2-induced cytotoxicity, DNA strand breaks, and apoptosis were detected at concentrations as low as 10–25 µmol/L. On the other hand, these flavonoids induced cytotoxicity, DNA strand breaks, oligonucleosomal DNA fragmentation, and caspase activation at concentrations between 50 and 250 µmol/L. Published data on quercetin pharmacokinetics in humans suggest that a dietary supplement of 1–2 g of quercetin may result in plasma concentrations between 10 and 50 µmol/L. Our data suggest that cytoprotective concentrations of some flavonoids are lower by a factor of 5–10 than their DNA-damaging and proapoptotic concentrations.

[proteomist]

Please note, the text I've highlighted in bold below should read 'up to 1.2 [micro]M resveratrol was observed in the plasma.' Not 1.2 M.

J. Agric. Food Chem., 52 (4), 935 -942, 2004. 10.1021/jf030582e S0021-8561(03)00582-X
Web Release Date: January 23, 2004
Copyright � 2004 American Chemical Society

Urinary and Plasma Levels of Resveratrol and Quercetin in Humans, Mice, and Rats after Ingestion of Pure Compounds and Grape Juice

Xiaofeng Meng, Pius Maliakal, Hong Lu, Mao-Jung Lee, and Chung S. Yang*

Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, New Jersey 08854

Received for review August 7, 2003. Revised manuscript received December 3, 2003. Accepted December 5, 2003. This work was supported in part by the California Grape Commission (Fresno, CA).

Abstract:

The present study investigates the bioavailability of resveratrol and quercetin in humans, mice, and rats after oral ingestion of grape juice preparations or pure aglycones. Oral administration of resveratrol and quercetin to humans yielded detectable levels of resveratrol, quercetin, and their derivatives in the plasma and urine. Urinary levels of resveratrol, quercetin, and their metabolites were observed in human subjects receiving 600 and 1200 mL of grape juice, whereas quercetin metabolites were identified in urine samples even after receiving 200 mL of grape juice. The cumulative amounts of resveratrol and quercetin excreted in the urine of mice receiving concentrated grape juice for 4 days were 2.3 and 0.7% of the ingested doses, respectively. After i.g. administration of resveratrol to rats (2 mg/kg), up to 1.2 M resveratrol was observed in the plasma. The study demonstrates that the glycoside forms of resveratrol and quercetin in grape juice are absorbed to a lesser extent than the aglycones.

Keywords: Resveratrol; quercetin; grape juice; human; rodents; plasma; urine

[malbecman]

Phew! I was wondering. I hope I dont have anything that is Molar in concentration in my plasma (altho I seem to recall blood is ~1% salt).

Please note, the text I've highlighted in bold below should read 'up to 1.2 [micro]M resveratrol was observed in the plasma.' Not 1.2 M.

J. Agric. Food Chem., 52 (4), 935 -942, 2004. 10.1021/jf030582e S0021-8561(03)00582-X
Web Release Date: January 23, 2004
Copyright � 2004 American Chemical Society

Urinary and Plasma Levels of Resveratrol and Quercetin in Humans, Mice, and Rats after Ingestion of Pure Compounds and Grape Juice

Xiaofeng Meng, Pius Maliakal, Hong Lu, Mao-Jung Lee, and Chung S. Yang*

Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, New Jersey 08854

Received for review August 7, 2003. Revised manuscript received December 3, 2003. Accepted December 5, 2003. This work was supported in part by the California Grape Commission (Fresno, CA).

Abstract:

The present study investigates the bioavailability of resveratrol and quercetin in humans, mice, and rats after oral ingestion of grape juice preparations or pure aglycones. Oral administration of resveratrol and quercetin to humans yielded detectable levels of resveratrol, quercetin, and their derivatives in the plasma and urine. Urinary levels of resveratrol, quercetin, and their metabolites were observed in human subjects receiving 600 and 1200 mL of grape juice, whereas quercetin metabolites were identified in urine samples even after receiving 200 mL of grape juice. The cumulative amounts of resveratrol and quercetin excreted in the urine of mice receiving concentrated grape juice for 4 days were 2.3 and 0.7% of the ingested doses, respectively. After i.g. administration of resveratrol to rats (2 mg/kg), up to 1.2 M resveratrol was observed in the plasma. The study demonstrates that the glycoside forms of resveratrol and quercetin in grape juice are absorbed to a lesser extent than the aglycones.

Keywords: Resveratrol; quercetin; grape juice; human; rodents; plasma; urine

[xanadu]

I've noticed many of the effects mentioned for t-res and I only take around 60 to 70mg per day. That seems like a big dose to me. Yes, it may be placebo but I noticed on 20mg per day that I was getting more energy and a little harder to sleep. On the higher doses I was getting an elevated mood, more difficulty sleeping and some degree of stimulation like feeling hyper and aggressive. I don't know why I would feel that on such a small dose. I do take many other things which may synergize with it. For one thing, I take piracetam which I've already noticed increases the effects of other drugs, both stimulants and depressants.

As a matter of fact, I find that around 70mg per day is a little high for me and I'm cutting back a bit. I use BAC 50% mix and have had no laxative effects though perhaps a little more gas. I really like the effects though the overaggression is not so great. I can go from mellow to mad in an instant which I don't like. I think I will stay at around 60mg per day and see how it goes.

[Brainbox]

After spending some more time reading about the study of Sinclair, I do not understand the rationale behind the design of it.

What could be the reason not to include a fourth group of mice that were given a normal diet with added resveratrol? If you are investing in a expensive study, why not add a few more mice?

Is there any reason (biological, statistical, economical or whatever) not to do that? I mean, at the expense of a few extra $$ the practical value of the study could have been magnitudes better IMHO. [glasses]

[VP.]

What could be the reason not to include a fourth group of mice that were given a normal diet with added resveratrol? If you are investing in a expensive study, why not add a few more mice?

That protocol is being tested. It's just too early to release the full study since many of the mice controls and +RSV mice are still alive. Expect a full report later this year after SIRT goes public.

[niner]

What could be the reason not to include a fourth group of mice that were given a normal diet with added resveratrol? If you are investing in a expensive study, why not add a few more mice?

Is there any reason (biological, statistical, economical or whatever) not to do that? I mean, at the expense of a few extra $$ the practical value of the study could have been magnitudes better IMHO.

Maybe they were worried about generating a negative result. The mice on the high fat diet were an easier target, where they were more likely to see a positive outcome. A negative outcome with mice on a normal diet may have been irrelevant, since mice are not people, but it would have greatly clouded the issue. Even a neutral outcome would have clouded the issue. It's hard at this point to make a business case for any other choice, as far as Sirtris is concerned. "Clouding the issue" in this case might have meant losing momentum or losing funding, neither of which would have been good for Sirtris, or ultimately, us.

[Anthony_Loera]

Hi, I asked this before, but got no respnses.

Is anyone taking Resveratrol in another method besides orally? One of my suppliers mentioned the 98% resveratrol was being taken by injection in her country in some instances.

I personally dont like needles, and wondered if anyone here knew of someone who was doing this.

Anthony