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Salicyic Acit Strongly Inhibits Sulfation of Resveratrol


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#1 maxwatt

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Posted 27 December 2007 - 10:54 PM


I came across this and thought it would interest some here.

Xenobiotica. 2000 Jun;30(6):609-17.Links
Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum.De Santi C, Pietrabissa A, Spisni R, Mosca F, Pacifici GM.
Department of Neurosciences, Medical School, Pisa, Italy.

1. Resveratrol, a polyphenolic compound present in grapes and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. It is present in the diet, and the hepatic and duodenal sulphation might limit the bioavailability of this compound. The aim was to study the sulphation of resveratrol in the human liver and duodenum. 2. A simple and reproducible radiometric assay for resveratrol sulphation was developed. It employed 3'-phosphoadenosine-5'-phosphosulphate-[35S] as the sulphate donor and the rates of resveratrol sulphation (mean +/- SD, pmol/min/mg cytosolic protein) were 90 +/- 21 (liver, n = 10) and 74 +/- 60 (duodenum, n = 10, p = 0.082). 3. Resveratrol sulphotransferase followed Michaelis-Menten kinetics and Km (mean +/- SD; microM) was 0.63 +/- 0.03 (liver, n = 5) and 0.50 +/- 0.26 (duodenum, n = 5, p = 0.39) and Vmax (mean +/- SD, pmol/min/mg cytosolic protein) were 125 +/- 31 (liver, n = 5) and 129 +/- 85 (duodenum, n = 5, p = 0.62). 4. Resveratrol sulphation was inhibited by the flavonoid quercetin, by mefenamic acid and salicylic acid, two commonly used non-steroidal anti-inflammatory drugs. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. The potent inhibition of resveratrol sulphation by quercetin, a flavonoid present in wine, fruits and vegetables, suggests that compounds present in the diet may inhibit the sulphation of resveratrol, thus improving its bioavailability.

PMID: 10923862


PS I really should fix the spelling before I post. :-D

Edited by maxwatt, 28 December 2007 - 02:56 AM.


#2 missminni

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Posted 28 December 2007 - 12:22 AM

I came across this and thought it would interest some here.

Xenobiotica. 2000 Jun;30(6):609-17.Links
Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum.De Santi C, Pietrabissa A, Spisni R, Mosca F, Pacifici GM.
Department of Neurosciences, Medical School, Pisa, Italy.

1. Resveratrol, a polyphenolic compound present in grapes and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. It is present in the diet, and the hepatic and duodenal sulphation might limit the bioavailability of this compound. The aim was to study the sulphation of resveratrol in the human liver and duodenum. 2. A simple and reproducible radiometric assay for resveratrol sulphation was developed. It employed 3'-phosphoadenosine-5'-phosphosulphate-[35S] as the sulphate donor and the rates of resveratrol sulphation (mean +/- SD, pmol/min/mg cytosolic protein) were 90 +/- 21 (liver, n = 10) and 74 +/- 60 (duodenum, n = 10, p = 0.082). 3. Resveratrol sulphotransferase followed Michaelis-Menten kinetics and Km (mean +/- SD; microM) was 0.63 +/- 0.03 (liver, n = 5) and 0.50 +/- 0.26 (duodenum, n = 5, p = 0.39) and Vmax (mean +/- SD, pmol/min/mg cytosolic protein) were 125 +/- 31 (liver, n = 5) and 129 +/- 85 (duodenum, n = 5, p = 0.62). 4. Resveratrol sulphation was inhibited by the flavonoid quercetin, by mefenamic acid and salicylic acid, two commonly used non-steroidal anti-inflammatory drugs. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. The potent inhibition of resveratrol sulphation by quercetin, a flavonoid present in wine, fruits and vegetables, suggests that compounds present in the diet may inhibit the sulphation of resveratrol, thus improving its bioavailability.

PMID: 10923862

How convenient. Aspirin! Well that certainly mitigates the cost.

Click HERE to rent this advertising spot to support LongeCity (this will replace the google ad above).

#3 stephen_b

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Posted 28 December 2007 - 02:22 AM

Nice find! Any idea how much aspirin would be needed?

Stephen

#4 sUper GeNius

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Posted 28 December 2007 - 02:36 AM

I came across this and thought it would interest some here.

Xenobiotica. 2000 Jun;30(6):609-17.Links
Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum.De Santi C, Pietrabissa A, Spisni R, Mosca F, Pacifici GM.
Department of Neurosciences, Medical School, Pisa, Italy.

1. Resveratrol, a polyphenolic compound present in grapes and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. It is present in the diet, and the hepatic and duodenal sulphation might limit the bioavailability of this compound. The aim was to study the sulphation of resveratrol in the human liver and duodenum. 2. A simple and reproducible radiometric assay for resveratrol sulphation was developed. It employed 3'-phosphoadenosine-5'-phosphosulphate-[35S] as the sulphate donor and the rates of resveratrol sulphation (mean +/- SD, pmol/min/mg cytosolic protein) were 90 +/- 21 (liver, n = 10) and 74 +/- 60 (duodenum, n = 10, p = 0.082). 3. Resveratrol sulphotransferase followed Michaelis-Menten kinetics and Km (mean +/- SD; microM) was 0.63 +/- 0.03 (liver, n = 5) and 0.50 +/- 0.26 (duodenum, n = 5, p = 0.39) and Vmax (mean +/- SD, pmol/min/mg cytosolic protein) were 125 +/- 31 (liver, n = 5) and 129 +/- 85 (duodenum, n = 5, p = 0.62). 4. Resveratrol sulphation was inhibited by the flavonoid quercetin, by mefenamic acid and salicylic acid, two commonly used non-steroidal anti-inflammatory drugs. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. The potent inhibition of resveratrol sulphation by quercetin, a flavonoid present in wine, fruits and vegetables, suggests that compounds present in the diet may inhibit the sulphation of resveratrol, thus improving its bioavailability.

PMID: 10923862


I think you just refined the French Paradox. Drink enough wine to create a hangover. Wakeup, gulp down aspirin to relieve the pounding headache. Start drinking again. Explains alot.

Edited by FuLL meMbeR, 28 December 2007 - 02:48 AM.


#5 VP.

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Posted 28 December 2007 - 03:15 AM

Nice find Max. I was taking a baby aspirin everyday with my resveratrol and other supplements. After looking at my blood work my doctor said don't bother with the aspirin. I will start back up tonight. :-D

#6 sUper GeNius

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Posted 28 December 2007 - 03:23 AM

Nice find Max. I was taking a baby aspirin everyday with my resveratrol and other supplements. After looking at my blood work my doctor said don't bother with the aspirin. I will start back up tonight. :-D


Or just eat an apple.

#7 Hedgehog

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Posted 28 December 2007 - 03:30 AM

nice find. I actually found a compound that will inhibit the sulfonating enzymes in the picomolar range. I'm going to test my new formulation in my bioavailibity study. What is going to be cool is that on my HPLC assay I should be able to hopefully watch the products Trans-resveratrol-3-O-glucuronides and Trans-Resveratrol-3-O-sulfates decrease while keeping my Trans-Resveratrol active. I also got funding from a person to conduct a larger study!

#8 edward

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Posted 28 December 2007 - 03:37 AM

so we have 90 (liver) and 74 (duodenum) <--- this is baseline sulphation


.......... 53 (liver) and 66 (duodenum) <--- this is with aspirin (good but not amazing)

.......... 12 (liver) and 15 (duodenum) <--- this is with quercetin (amazing)


looks like aspirin is a great addition but nothing like the inhibition of sulphation you get with quercetin, which again brings up the whole risk of SIRT inhibition vs. the reward of decreased sulphation... sadly

note: anyone ever tried to cap or even dose bulk quercetin powder (it is the most bizarre stuff, it gets electrically charged and goes everywhere, not recommended)

#9 niner

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Posted 28 December 2007 - 05:16 AM

nice find. I actually found a compound that will inhibit the sulfonating enzymes in the picomolar range. I'm going to test my new formulation in my bioavailibity study. What is going to be cool is that on my HPLC assay I should be able to hopefully watch the products Trans-resveratrol-3-O-glucuronides and Trans-Resveratrol-3-O-sulfates decrease while keeping my Trans-Resveratrol active. I also got funding from a person to conduct a larger study!

Hedgehog, this is awesome! What is your sulfation inhibitor? Quercetin? The reported picomolar inhibition for quercetin is actually kind of hard to believe. I think that quercetin itself is very rapidly conjugated, for what it's worth.

#10 niner

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Posted 28 December 2007 - 05:40 AM

so we have 90 (liver) and 74 (duodenum) <--- this is baseline sulphation

.......... 53 (liver) and 66 (duodenum) <--- this is with aspirin (good but not amazing)

.......... 12 (liver) and 15 (duodenum) <--- this is with quercetin (amazing)

Edward, the first numbers (90 and 74) are rates of sulfation, but the other numbers are not. They are IC50 values, the concentration required to inhibit the enzyme 50%, i.e., cut the sulfation rate in half. Aspirin's are 53 and 66 micromolar, while quercetin's are 12 and 15 picomolar(!) A picomole is one millionth of a micromole. This means two things:

Aspirin is not a very strong sulfation inhibitor. According to a human PK study in http://jcp.sagepub.c...ract/35/12/1181 the maximum plasma concentration reached with an 80mg oral dose of (baby) aspirin was 1ug/ml = 5.5uM, or only one tenth of the IC50. Further, the half life of aspirin is only 24 minutes, although it is converted to salicylic acid, which has a much longer half life and develops higher plasma concentrations. Unless salicylic acid is also a sulfation inhibitor, I think you are going to need a dangerous dose of aspirin in order to get decent inhibition, and even then it will not last very long.

Quercetin, on the other hand, is over a million times more powerful than aspirin as a sulfation inhibitor, at least according to deSanti et al., the source of these numbers. To be honest, I kinda don't believe these numbers. A picomolar inhibitor of *anything* is rare. If these numbers are right, then we have to explain why we have any sulfation ability at all, given the level of quercetin intake in a decent diet. It may have something to do with quercetin being rapidly conjugated, but even so, I find this puzzling.

#11 Hedgehog

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Posted 28 December 2007 - 06:16 AM

nice find. I actually found a compound that will inhibit the sulfonating enzymes in the picomolar range. I'm going to test my new formulation in my bioavailibity study. What is going to be cool is that on my HPLC assay I should be able to hopefully watch the products Trans-resveratrol-3-O-glucuronides and Trans-Resveratrol-3-O-sulfates decrease while keeping my Trans-Resveratrol active. I also got funding from a person to conduct a larger study!

Hedgehog, this is awesome! What is your sulfation inhibitor? Quercetin? The reported picomolar inhibition for quercetin is actually kind of hard to believe. I think that quercetin itself is very rapidly conjugated, for what it's worth.


No its not quercetin. Pending my study I might have somebody formulate it. I think it might have to be time release formulation :(

Anyways, Thanks to the funding I have ordered all my testing and products to conduct the study.

If it does work it is going to take a lot more studys to determine the correct amounts of each thing. Max the [Res] and Min potential harmful degradents.

I personally think large doses of Res or other herbs are going to be dangerous to the body in the long run.

#12 HaloTeK

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Posted 28 December 2007 - 08:31 AM

I think people tend to forget that the human body views many if not all plant compunds as a toxins. Whether the compound in the end exerts a beneficial effect is another thing. The fact that resveratrol needs to be conjugated at all spells this out all the more. The fact that it mimics caloric restriction is a side effect. Its very possible that certain individuals who are out for top human performance would want to forgo resveratrol because it might hamper certain functions (high end oxidative capacity- but for the majority- the little side effects are worth the longevity advantages. Let us not forget that Intermittant fasting seems to confer all the same benefits and more that caloric restriction gives. And- you get to eat almost your normal daily allowances of food-albeit, intermittantly! Also, taking too many anti-oxidants seems way conterproductive. I don't need to quote the multitude of literature on that. We need to really figure out quantitatively what a good dose of resveratrol is- and to make sure it absorbed and not conjugated (or at least not completely).

Sorry about spelling and other issues- i view forums as random musings.

#13 sUper GeNius

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Posted 28 December 2007 - 09:07 AM

[quote name='HaloTeK' date='28-Dec 2007, 03:31 AM' post='216079']
I think people tend to forget that the human body views many if not all plant compunds as a toxins. Whether the compound in the end exerts a beneficial effect is another thing. The fact that resveratrol needs to be conjugated at all spells this out all the more. The fact that it mimics caloric restriction is a side effect. Its very possible that certain individuals who are out for top human performance would want to forgo resveratrol because it might hamper certain functions (high end oxidative capacity- but for the majority- the little side effects are worth the longevity advantages. Let us not forget that Intermittant fasting seems to confer all the same benefits and more that caloric restriction gives. And- you get to eat almost your normal daily allowances of food-albeit, intermittantly!

Where is the proof in humans?

#14 edward

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Posted 29 December 2007 - 07:04 PM

so we have 90 (liver) and 74 (duodenum) <--- this is baseline sulphation

.......... 53 (liver) and 66 (duodenum) <--- this is with aspirin (good but not amazing)

.......... 12 (liver) and 15 (duodenum) <--- this is with quercetin (amazing)

Edward, the first numbers (90 and 74) are rates of sulfation, but the other numbers are not. They are IC50 values, the concentration required to inhibit the enzyme 50%, i.e., cut the sulfation rate in half. Aspirin's are 53 and 66 micromolar, while quercetin's are 12 and 15 picomolar(!) A picomole is one millionth of a micromole. This means two things:

Aspirin is not a very strong sulfation inhibitor. According to a human PK study in http://jcp.sagepub.c...ract/35/12/1181 the maximum plasma concentration reached with an 80mg oral dose of (baby) aspirin was 1ug/ml = 5.5uM, or only one tenth of the IC50. Further, the half life of aspirin is only 24 minutes, although it is converted to salicylic acid, which has a much longer half life and develops higher plasma concentrations. Unless salicylic acid is also a sulfation inhibitor, I think you are going to need a dangerous dose of aspirin in order to get decent inhibition, and even then it will not last very long.

Quercetin, on the other hand, is over a million times more powerful than aspirin as a sulfation inhibitor, at least according to deSanti et al., the source of these numbers. To be honest, I kinda don't believe these numbers. A picomolar inhibitor of *anything* is rare. If these numbers are right, then we have to explain why we have any sulfation ability at all, given the level of quercetin intake in a decent diet. It may have something to do with quercetin being rapidly conjugated, but even so, I find this puzzling.


Thanks Niner for clearing up my confusion.

#15 cleargreen

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Posted 30 December 2007 - 05:42 AM

In http://www.longevine...io-Availability they talk about quercetin as a sulfation inhibitor for resveratrol. However, they cite an article that says that glucuronidation of resveratrol by the liver may actually be beneficial, as it may increase its half life and allow it to target specific tissues more efficiently. So sulfation is bad but glucuronidation is good? Any thoughts?

#16 StrangeAeons

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Posted 30 December 2007 - 07:00 AM

I'm just a lowly paramedic student who still hasn't caught on to all of your science, but does the fact that aspirin is ACETYLsalicylic acid not change things just a bit? Perhaps I'm wrong and they acetyl part gets knocked off somewhere in the enteral route... or perhaps you should swallow acne gel instead...

#17 niner

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Posted 30 December 2007 - 07:39 AM

I'm just a lowly paramedic student who still hasn't caught on to all of your science, but does the fact that aspirin is ACETYLsalicylic acid not change things just a bit? Perhaps I'm wrong and they acetyl part gets knocked off somewhere in the enteral route... or perhaps you should swallow acne gel instead...

Ahem... once again, a "lowly" student has the clue. You're right, PetaKiaRose! The abstract at the top of the thread says "salicylic acid", not aspirin. It quickly got transmogrified in all subsequent posts and I didn't notice it. Aspirin is pretty rapidly hydrolyzed to salicylic acid in vivo, and the salicylic acid has a much longer half life than the aspirin. It also has higher blood levels; in some cases much higher. In my post above, I stupidly wrote "Unless salicylic acid is also a sulfation inhibitor, I think you are going to need a dangerous dose of aspirin in order to get decent inhibition, and even then it will not last very long." So, since salicylic acid IS a sulfation inhibitor, it looks like while a baby aspirin wouldn't get you there, (I think that's around 20 uM salicylic acid) a regular aspirin probably would. Aspirin is a somewhat gnarly drug with respect to induction of GI bleeds and the like, but it's cheap and available. Could be something to this after all. If you try it, take the aspirin about an hour before the res.

#18 Mixter

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Posted 30 December 2007 - 11:37 AM

1. Resveratrol, a polyphenolic compound present in grapes and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. It is present in the diet, and the hepatic and duodenal sulphation might limit the bioavailability of this compound. The aim was to study the sulphation of resveratrol in the human liver and duodenum. 2. A simple and reproducible radiometric assay for resveratrol sulphation was developed. It employed 3'-phosphoadenosine-5'-phosphosulphate-[35S] as the sulphate donor and the rates of resveratrol sulphation (mean +/- SD, pmol/min/mg cytosolic protein) were 90 +/- 21 (liver, n = 10) and 74 +/- 60 (duodenum, n = 10, p = 0.082). 3. Resveratrol sulphotransferase followed Michaelis-Menten kinetics and Km (mean +/- SD; microM) was 0.63 +/- 0.03 (liver, n = 5) and 0.50 +/- 0.26 (duodenum, n = 5, p = 0.39) and Vmax (mean +/- SD, pmol/min/mg cytosolic protein) were 125 +/- 31 (liver, n = 5) and 129 +/- 85 (duodenum, n = 5, p = 0.62). 4. Resveratrol sulphation was inhibited by the flavonoid quercetin, by mefenamic acid and salicylic acid, two commonly used non-steroidal anti-inflammatory drugs. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. The potent inhibition of resveratrol sulphation by quercetin, a flavonoid present in wine, fruits and vegetables, suggests that compounds present in the diet may inhibit the sulphation of resveratrol, thus improving its bioavailability.


Also note that quercetin inhibits the sulfation even more, and is the best candidate in this study. And more than a daily 3-4 baby aspirin might damage your stomach lining. Many suppliers already add quercetin to their resveratrol supplements to enhance bioavailability,.. I'm inclined to believe that taking it with a little of whole grape+grape speed extract gives even more benefits than quercetin alone, as you get a lot of compounds similar to TRES, and consider taking it this way. If you want a higher SIRT activation, you could always add more resveratrol to grape-/grape seed extract.

Edited by mixter, 30 December 2007 - 11:38 AM.


#19 Mixter

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Posted 30 December 2007 - 11:40 AM

I'm just a lowly paramedic student who still hasn't caught on to all of your science, but does the fact that aspirin is ACETYLsalicylic acid not change things just a bit? Perhaps I'm wrong and they acetyl part gets knocked off somewhere in the enteral route... or perhaps you should swallow acne gel instead...


No, but willow bark extract, the natural source of salicylic acid... that may be a better option than ASS, actually.

#20 maxwatt

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Posted 30 December 2007 - 02:08 PM

In http://www.longevine...io-Availability they talk about quercetin as a sulfation inhibitor for resveratrol. However, they cite an article that says that glucuronidation of resveratrol by the liver may actually be beneficial, as it may increase its half life and allow it to target specific tissues more efficiently. So sulfation is bad but glucuronidation is good? Any thoughts?


The source is suspect; he twists everything to make his product look good, even when he ends up contradicting himself. Having corresponded with him, I think it's not venality; the man is truly manic.

I had trouble believing the anti-sulfation figures for resveratrol, thought they were a misprint, but if they are true, one would need very little quercetin. So little that it would not act to block SirT1. However the amounts most manufacturers add to their formulations is the same order of magnitude as the amount of resveratrol, so it's counter productive. I think 1/100th the resveratrol amount would be appropriate.

I've also thought that just taking a higher resveratrol dose would swamp the sulfation mechanism, so if might be an answer. I've misplaced the reference, unfortunately, but I thought I saw an abstract where human blood levels were measured and they found just that. If anyone can turn it up, thanks.

edit to clean up spelling errors

Edited by maxwatt, 31 December 2007 - 02:50 AM.


#21 steelheader

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Posted 30 December 2007 - 07:59 PM

In http://www.longevine...io-Availability they talk about quercetin as a sulfation inhibitor for resveratrol. However, they cite an article that says that glucuronidation of resveratrol by the liver may actually be beneficial, as it may increase its half life and allow it to target specific tissues more efficiently. So sulfation is bad but glucuronidation is good? Any thoughts?


The source is suspect; he twists everything to make his product look good, even when he ends up contradicting himself. Having corresponded with him, I think it's not venality; the man is truly manic.

I had trouple believing the anti-sulfonation figures for resveratrol, thought htey were a missprint, but if they are true, one would need very little quercetin. So little that it would not act to block SirT1. However the amounts most manufacturers add to their formulations is the same order of magnitude as the amount of resveratrol, so it's counter productive. I think 1/100th the resveratrol amount would be appropriate.

I've also thought that just taking a higher resveratrol dose would swamp the sulfonation mechanism, so if might be an answer. I've misplaced the reference, unfortunately, but I thought I saw an abstract where human blood levels were measured and they found just that. If anyone can turn it up, thanks.


Maxwatt, when you tried quercetin with poor results as far as longer term pain relief was concerned, how much were you using? Are you planning to experiment with 1/100th the resveratrol amount?

#22 krillin

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Posted 30 December 2007 - 11:24 PM

Maxwatt, when you tried quercetin with poor results as far as longer term pain relief was concerned, how much were you using? Are you planning to experiment with 1/100th the resveratrol amount?


http://www.imminst.o...&...st&p=204877

500 mg. There was some bromelain in it too. The reason people think it helps is that it is preferentially sulfonated, sparing resveratrol so that in theory more of it gets to the cells. I found it weakened the effect of the resveratrol I was taking, in that the anti-arthritic effect I obtained from resveratrol disappeared when I added 500 mg of quercetin to my regimen. (I was taking about 1.5 gram of resveratrol at the time.)


http://www.imminst.o...&...st&p=191631

I was taking 250 mg quercetin per 1 gram resveratrol.



#23 maxwatt

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Posted 31 December 2007 - 02:55 AM

....
Maxwatt, when you tried quercetin with poor results as far as longer term pain relief was concerned, how much were you using? Are you planning to experiment with 1/100th the resveratrol amount?


I may sometime, but I am not going out of my way to acquire quercetin in the form or dosage necessary to do this.
I have large quantities of inexpensive resveratrol available, and using an extra 500 mg per dose to inhibit sulfation is a good option for me. I did find I did not get the deep-joint, long-term pain and inflammation relief until my dose exceeded 500 mg.

PS: Thanks, Krillin, for finding my previous answer to the question.

Edited by maxwatt, 31 December 2007 - 02:57 AM.


#24 niner

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Posted 31 December 2007 - 04:15 AM

I had trouble believing the anti-sulfation figures for resveratrol, thought they were a misprint, but if they are true, one would need very little quercetin. So little that it would not act to block SirT1. However the amounts most manufacturers add to their formulations is the same order of magnitude as the amount of resveratrol, so it's counter productive. I think 1/100th the resveratrol amount would be appropriate.

I've also thought that just taking a higher resveratrol dose would swamp the sulfation mechanism, so if might be an answer. I've misplaced the reference, unfortunately, but I thought I saw an abstract where human blood levels were measured and they found just that. If anyone can turn it up, thanks.

Quercetin is heavily conjugated just like all these polyphenols are, so that at least partially explains the need for more, but I'm with you on the hard to believe aspect of picomolar quercetin sulfation inhibition.

Could this be the paper you were thinking of? It's not human blood levels, but the Caco2 model has the metabolic systems of the human gut, so it's a reasonable model. (It is widely used for permeability testing.) Here they did see an enhancement of 3.5X in transport of resveratrol at concentrations of 200uM. The only reason I don't laugh at that concentration is because in the gut, it's at least conceivable that one might obtain local concentrations of that magnitude on the lumenal side. This is why I take resveratrol on an empty stomach; it's an attempt to flood the gut and swamp the gut metabolic enzymes.

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



#25 maxwatt

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Posted 31 December 2007 - 04:30 PM

I had trouble believing the anti-sulfation figures for resveratrol, thought they were a misprint, but if they are true, one would need very little quercetin. So little that it would not act to block SirT1. However the amounts most manufacturers add to their formulations is the same order of magnitude as the amount of resveratrol, so it's counter productive. I think 1/100th the resveratrol amount would be appropriate.

I've also thought that just taking a higher resveratrol dose would swamp the sulfation mechanism, so if might be an answer. I've misplaced the reference, unfortunately, but I thought I saw an abstract where human blood levels were measured and they found just that. If anyone can turn it up, thanks.

Quercetin is heavily conjugated just like all these polyphenols are, so that at least partially explains the need for more, but I'm with you on the hard to believe aspect of picomolar quercetin sulfation inhibition.

Could this be the paper you were thinking of? It's not human blood levels, but the Caco2 model has the metabolic systems of the human gut, so it's a reasonable model. (It is widely used for permeability testing.) Here they did see an enhancement of 3.5X in transport of resveratrol at concentrations of 200uM. The only reason I don't laugh at that concentration is because in the gut, it's at least conceivable that one might obtain local concentrations of that magnitude on the lumenal side. This is why I take resveratrol on an empty stomach; it's an attempt to flood the gut and swamp the gut metabolic enzymes.

SNIP
PMID: 16952002


That could be the paper I was told about. I don't agree with you about taking resveratrol on an empty stomach. Most fruits and vegetables have quite a few substances that compet with resveratrol for glucoronation and sulfation, so I think you can get higher serum levels with a little grapefruit or orange juice, or broccoli or kale or onions or Confit Vegetal, Duck a l'Orange avec Haricot Vert, Sorbet de Citron, Kasha varnishes mit carrots und celery......

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#26 krillin

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Posted 02 January 2008 - 12:57 AM

If it helps any, here's a paper that Niner found back in April which includes a review of plasma quercetin levels attained by various quercetin intakes.

http://jn.nutrition..../full/135/3/525




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