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Acetylated Resveratrol


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Poll: Would you be interested? (33 member(s) have cast votes)

Actylated Resveratrol

  1. Definitely (23 votes [69.70%])

    Percentage of vote: 69.70%

  2. No (10 votes [30.30%])

    Percentage of vote: 30.30%

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#1 Reverse

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Posted 29 April 2008 - 12:33 AM


I first want to say that this forum is quite remarkable. I had never seen it before today and there is a lot of good information on here, not just a bunch of people screaming about things they know nothing about as with a lot of health forums across the internet. Secondly I want to say that I am by no means adverstising this product, I just want to gauge interest in it and I felt like this was a great place to start. I work for a dietary supplement company and we will soon be releasing 3,5,4'-triacetyl resveratrol. It will be in effective dosages (not yet determined) and contain ingredients such as piperine and others to decrease enzymatic activity and increase enzymatic competition. We are toying with the idea of using compounds such as HPBC and flax oil as a delivery system in a liquid capsule. After a lot of research we felt as though this compound was the best of both worlds when it comes to increasing lipophilicity without going as far as creating a trimethoxy compound which in a few studies has shown to have potent anti-tumor properties but negligble antioxidant properties. Would any of you be interested in this sort of product? What would be your concerns? I know one of your main concerns would be price but I can assure you we are not here to rip anyone off or provide a product that contains minute amounts of active ingredients. I have seen this too much in this industry and it is ridiculous. I am not sure of price just yet but it should not exceed $50.

#2 tintinet

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Posted 29 April 2008 - 01:22 AM

I first want to say that this forum is quite remarkable. I had never seen it before today and there is a lot of good information on here, not just a bunch of people screaming about things they know nothing about as with a lot of health forums across the internet. Secondly I want to say that I am by no means adverstising this product, I just want to gauge interest in it and I felt like this was a great place to start. I work for a dietary supplement company and we will soon be releasing 3,5,4'-triacetyl resveratrol. It will be in effective dosages (not yet determined) and contain ingredients such as piperine and others to decrease enzymatic activity and increase enzymatic competition. We are toying with the idea of using compounds such as HPBC and flax oil as a delivery system in a liquid capsule. After a lot of research we felt as though this compound was the best of both worlds when it comes to increasing lipophilicity without going as far as creating a trimethoxy compound which in a few studies has shown to have potent anti-tumor properties but negligble antioxidant properties. Would any of you be interested in this sort of product? What would be your concerns? I know one of your main concerns would be price but I can assure you we are not here to rip anyone off or provide a product that contains minute amounts of active ingredients. I have seen this too much in this industry and it is ridiculous. I am not sure of price just yet but it should not exceed $50.


Likely I'd be interested, depending upon pricing and scientific support. $50 for how much?

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#3 maxwatt

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Posted 29 April 2008 - 01:42 AM

Sinclair's group mentioned an acetylated resveratrol in one of their papers. Though it was more potent than resveratrol, it was not fully acetylated. That I would be interested in. I wouldn't be interested in the tri-acetylated form until I saw some studies or test results. We can't be sure it will be properly de-acetylated in the body, or that it activates Sirt1.

Edited by maxwatt, 29 April 2008 - 03:53 AM.


#4 niner

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Posted 29 April 2008 - 01:58 AM

If memory serves me correctly, according to one of the papers that came out of Sinclair's group, with anything but an OH the 4' position, you lose the property of activating Sirt1. You can find discussion of this in the first five pages or so of the 500-mg club thread. So despite the improved solubility, it probably would not be effective for our purposes. I would want to see studies or tests for sirtuin activation.

Another substance they worked with, trans-3,5-acetyl, 4'-hydroxy-stilbene, was reported to an effective sirtuin agonist, and was thought to remain inside the cell being de-acetylated. That would be be a sort of super-time release resveratrol, and would get around the problems of glucuronation and sulfation. The synthesis is not so simple as for tri-acetyl resveratrol. But that I would be interested in.

The 4' acetyl was inactive in vitro, but in vivo it was very active; moreso than resveratrol. The thinking was that the acetyl was cleaved by an intracellular esterase. I'm not sure that you would even need to peracetylate the molecule, just hit the 4'. There's an enzymatic synthesis that does that, although it might be cheaper to hit the whole thing chemically. The problem with either of these approaches is that it's no longer a natural product. Once it's modified, you're dealing with a New Chemical Entity (NCE) and the laws are different, aren't they? Could you get around it by finding a natural form of it, then just say you were synthesizing that? Otherwise, Sirtris could have used acetylated resveratrol instead of regular resveratrol in SRT501. At least that would have made sense, given the substantial increase in activity (tenfold(?), if I remember correctly) that was seen in vivo, compared to resveratrol. When 501 first came out and there wasn't any information about what it was, I thought that it was acetylated resveratrol.

#5 sUper GeNius

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Posted 29 April 2008 - 02:13 AM

If memory serves me correctly, according to one of the papers that came out of Sinclair's group, with anything but an OH the 4' position, you lose the property of activating Sirt1. You can find discussion of this in the first five pages or so of the 500-mg club thread. So despite the improved solubility, it probably would not be effective for our purposes. I would want to see studies or tests for sirtuin activation.

Another substance they worked with, trans-3,5-acetyl, 4'-hydroxy-stilbene, was reported to an effective sirtuin agonist, and was thought to remain inside the cell being de-acetylated. That would be be a sort of super-time release resveratrol, and would get around the problems of glucuronation and sulfation. The synthesis is not so simple as for tri-acetyl resveratrol. But that I would be interested in.

The 4' acetyl was inactive in vitro, but in vivo it was very active; moreso than resveratrol. The thinking was that the acetyl was cleaved by an intracellular esterase. I'm not sure that you would even need to peracetylate the molecule, just hit the 4'. There's an enzymatic synthesis that does that, although it might be cheaper to hit the whole thing chemically. The problem with either of these approaches is that it's no longer a natural product. Once it's modified, you're dealing with a New Chemical Entity (NCE) and the laws are different, aren't they? Could you get around it by finding a natural form of it, then just say you were synthesizing that? Otherwise, Sirtris could have used acetylated resveratrol instead of regular resveratrol in SRT501. At least that would have made sense, given the substantial increase in activity (tenfold(?), if I remember correctly) that was seen in vivo, compared to resveratrol. When 501 first came out and there wasn't any information about what it was, I thought that it was acetylated resveratrol.


No worries. There's gotta be a little bit of the stuff in a peanut, right? What about fermented peanuts? Rancid peanuts?

#6 Reverse

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Posted 29 April 2008 - 02:30 PM

If memory serves me correctly, according to one of the papers that came out of Sinclair's group, with anything but an OH the 4' position, you lose the property of activating Sirt1. You can find discussion of this in the first five pages or so of the 500-mg club thread. So despite the improved solubility, it probably would not be effective for our purposes. I would want to see studies or tests for sirtuin activation.

Another substance they worked with, trans-3,5-acetyl, 4'-hydroxy-stilbene, was reported to an effective sirtuin agonist, and was thought to remain inside the cell being de-acetylated. That would be be a sort of super-time release resveratrol, and would get around the problems of glucuronation and sulfation. The synthesis is not so simple as for tri-acetyl resveratrol. But that I would be interested in.

The 4' acetyl was inactive in vitro, but in vivo it was very active; moreso than resveratrol. The thinking was that the acetyl was cleaved by an intracellular esterase. I'm not sure that you would even need to peracetylate the molecule, just hit the 4'. There's an enzymatic synthesis that does that, although it might be cheaper to hit the whole thing chemically. The problem with either of these approaches is that it's no longer a natural product. Once it's modified, you're dealing with a New Chemical Entity (NCE) and the laws are different, aren't they? Could you get around it by finding a natural form of it, then just say you were synthesizing that? Otherwise, Sirtris could have used acetylated resveratrol instead of regular resveratrol in SRT501. At least that would have made sense, given the substantial increase in activity (tenfold(?), if I remember correctly) that was seen in vivo, compared to resveratrol. When 501 first came out and there wasn't any information about what it was, I thought that it was acetylated resveratrol.


Thanks for the feedback guys. Actualy there is a reason we used the triacetylated version. To get the 4'-acetyl analogue you must pass right on by the triacetylted analogue using CA Lipase. CA Lipase is pretty expensive because it needs to be in a 1:1 ratio with the resveratrol, which would make it inefficient price wise. I have kept an eye on the steric effects of functional groups and the research that I have done suggests that even with somewhat larger functional groups steric effects do not play a part in activity. With this being said triacetyl resveratrol should last longer in the body since the group will either be broken down straight back to the hydroxy version, giving some more time to pass the liver, or the carbonyl group will be converted to a hydroxyl with the side chain intact. I was glad to read in a lot of threads here that people understood that you can not "predict" metabolism, we are talking about millions of enzymes throughout the body many of which we do not understand. One of the reasons we are using a lipophylic delivery system as well is to speed uptake in the intestines. We feel the faster the process the better the chances of high blood levels.

What additions would everyone like to see to this type of product? Quercetin, piperine, HPBC?

#7 Hedgehog

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Posted 29 April 2008 - 03:35 PM

Sinclair's group mentioned an acetylated resveratrol in one of their papers. Though it was more potent than resveratrol, it was not fully acetylated. That I would be interested in. I wouldn't be interested in the tri-acetylated form until I saw some studies or test results. We can't be sure it will be properly de-acetylated in the body, or that it activates Sirt1.



Furthermore, different structural components are responsible for the activities of isoflavones: the hydroxyl group at position 7 is required SIRT1Posted Image activation, a hydroxyl group at position 5 blocks SIRT1Posted Image activation, and the loss of the phenyl ring at position 3 or the 4' hydroxy or methoxy substituent blocks increased SIRT1Posted Image expression. [2008]

Do you have any evidence that it activates SIRT1? with a tri-methoxy resveratrol?

#8 malbecman

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Posted 29 April 2008 - 04:34 PM

I think you need another choice in your poll and that would be "Maybe". ;)

Would depend on cost, of course but like you said, the forum here is a group of generally pretty savvy folks and we would likely need to be swayed by at least some in vitro SIRT-1 activation assay results or some in vivo metabolism, IMHO.

I don't think most people would want additives but would prefer to do it themself, if at all. The general feeling I get here is that piperine has some negatives to its regular usage, for instance...

#9 stephen_b

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Posted 29 April 2008 - 05:22 PM

What additions would everyone like to see to this type of product? Quercetin, piperine, HPBC?

You might find some resistance to adding either quercetin or piperine to the mix. I would just as soon not have either one in the product.

Stephen

Edited by stephen_b, 29 April 2008 - 05:22 PM.


#10 Hedgehog

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Posted 29 April 2008 - 06:16 PM

If memory serves me correctly, according to one of the papers that came out of Sinclair's group, with anything but an OH the 4' position, you lose the property of activating Sirt1. You can find discussion of this in the first five pages or so of the 500-mg club thread. So despite the improved solubility, it probably would not be effective for our purposes. I would want to see studies or tests for sirtuin activation.

Another substance they worked with, trans-3,5-acetyl, 4'-hydroxy-stilbene, was reported to an effective sirtuin agonist, and was thought to remain inside the cell being de-acetylated. That would be be a sort of super-time release resveratrol, and would get around the problems of glucuronation and sulfation. The synthesis is not so simple as for tri-acetyl resveratrol. But that I would be interested in.

The 4' acetyl was inactive in vitro, but in vivo it was very active; moreso than resveratrol. The thinking was that the acetyl was cleaved by an intracellular esterase. I'm not sure that you would even need to peracetylate the molecule, just hit the 4'. There's an enzymatic synthesis that does that, although it might be cheaper to hit the whole thing chemically. The problem with either of these approaches is that it's no longer a natural product. Once it's modified, you're dealing with a New Chemical Entity (NCE) and the laws are different, aren't they? Could you get around it by finding a natural form of it, then just say you were synthesizing that? Otherwise, Sirtris could have used acetylated resveratrol instead of regular resveratrol in SRT501. At least that would have made sense, given the substantial increase in activity (tenfold(?), if I remember correctly) that was seen in vivo, compared to resveratrol. When 501 first came out and there wasn't any information about what it was, I thought that it was acetylated resveratrol.


Thanks for the feedback guys. Actualy there is a reason we used the triacetylated version. To get the 4'-acetyl analogue you must pass right on by the triacetylted analogue using CA Lipase. CA Lipase is pretty expensive because it needs to be in a 1:1 ratio with the resveratrol, which would make it inefficient price wise. I have kept an eye on the steric effects of functional groups and the research that I have done suggests that even with somewhat larger functional groups steric effects do not play a part in activity. With this being said triacetyl resveratrol should last longer in the body since the group will either be broken down straight back to the hydroxy version, giving some more time to pass the liver, or the carbonyl group will be converted to a hydroxyl with the side chain intact. I was glad to read in a lot of threads here that people understood that you can not "predict" metabolism, we are talking about millions of enzymes throughout the body many of which we do not understand. One of the reasons we are using a lipophylic delivery system as well is to speed uptake in the intestines. We feel the faster the process the better the chances of high blood levels.

What additions would everyone like to see to this type of product? Quercetin, piperine, HPBC?


I still think you need some of the -OH's for activation of SIRT1.

#11 Reverse

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Posted 29 April 2008 - 06:45 PM

If memory serves me correctly, according to one of the papers that came out of Sinclair's group, with anything but an OH the 4' position, you lose the property of activating Sirt1. You can find discussion of this in the first five pages or so of the 500-mg club thread. So despite the improved solubility, it probably would not be effective for our purposes. I would want to see studies or tests for sirtuin activation.

Another substance they worked with, trans-3,5-acetyl, 4'-hydroxy-stilbene, was reported to an effective sirtuin agonist, and was thought to remain inside the cell being de-acetylated. That would be be a sort of super-time release resveratrol, and would get around the problems of glucuronation and sulfation. The synthesis is not so simple as for tri-acetyl resveratrol. But that I would be interested in.

The 4' acetyl was inactive in vitro, but in vivo it was very active; moreso than resveratrol. The thinking was that the acetyl was cleaved by an intracellular esterase. I'm not sure that you would even need to peracetylate the molecule, just hit the 4'. There's an enzymatic synthesis that does that, although it might be cheaper to hit the whole thing chemically. The problem with either of these approaches is that it's no longer a natural product. Once it's modified, you're dealing with a New Chemical Entity (NCE) and the laws are different, aren't they? Could you get around it by finding a natural form of it, then just say you were synthesizing that? Otherwise, Sirtris could have used acetylated resveratrol instead of regular resveratrol in SRT501. At least that would have made sense, given the substantial increase in activity (tenfold(?), if I remember correctly) that was seen in vivo, compared to resveratrol. When 501 first came out and there wasn't any information about what it was, I thought that it was acetylated resveratrol.


Thanks for the feedback guys. Actualy there is a reason we used the triacetylated version. To get the 4'-acetyl analogue you must pass right on by the triacetylted analogue using CA Lipase. CA Lipase is pretty expensive because it needs to be in a 1:1 ratio with the resveratrol, which would make it inefficient price wise. I have kept an eye on the steric effects of functional groups and the research that I have done suggests that even with somewhat larger functional groups steric effects do not play a part in activity. With this being said triacetyl resveratrol should last longer in the body since the group will either be broken down straight back to the hydroxy version, giving some more time to pass the liver, or the carbonyl group will be converted to a hydroxyl with the side chain intact. I was glad to read in a lot of threads here that people understood that you can not "predict" metabolism, we are talking about millions of enzymes throughout the body many of which we do not understand. One of the reasons we are using a lipophylic delivery system as well is to speed uptake in the intestines. We feel the faster the process the better the chances of high blood levels.

What additions would everyone like to see to this type of product? Quercetin, piperine, HPBC?


I still think you need some of the -OH's for activation of SIRT1.



Problem is I have seen conflicting data on this. One study will say one thing, another will say something else. It is quite frustrating actually and there is definitely a lack of standardization in these studies. Our hopes, and I will admit this is purely theoretical due to the complexity of enzymatic metabolism in humans, is that it will be broken down to the hydroxl version then glucoronidized or sulfated after this. Due to the increased lipophilicity of the compound we will achieve much much faster absorption at least in hopes of making the first pass as quickly as possible. At current we have the dosage at 350mg of triacetylated resveratrol/serving (30 servings) and it will probably sell for $60 retail. We are not in the game to rip people off, the product is definitely expensive though (raw materials). Again it will be in liquid cap and be completely dissolved in a lipid delivery system. Many people on here take 1+ g/daily but we don't feel that using that high of a dosage is required to reap the health benefits, especially when using a derivative such as triacetylated or trimethoxy.

#12 Hedgehog

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Posted 29 April 2008 - 07:07 PM



Problem is I have seen conflicting data on this. One study will say one thing, another will say something else.
It is quite frustrating actually and there is definitely a lack of standardization in these studies. Our hopes, and I will admit this is purely theoretical due to the complexity of enzymatic metabolism in humans, is that it will be broken down to the hydroxl version then glucoronidized or sulfated after this. Due to the increased lipophilicity of the compound we will achieve much much faster absorption at least in hopes of making the first pass as quickly as possible. At current we have the dosage at 350mg of triacetylated resveratrol/serving (30 servings) and it will probably sell for $60 retail. We are not in the game to rip people off, the product is definitely expensive though (raw materials). Again it will be in liquid cap and be completely dissolved in a lipid delivery system. Many people on here take 1+ g/daily but we don't feel that using that high of a dosage is required to reap the health benefits, especially when using a derivative such as triacetylated or trimethoxy.



Do you have the studies that conflict? Sounds interesting... This sounds like a NCE, if you are NOT finding this compound in a plant you will need tox studies and clinical trials... which could be costly.

"In agreement with previous reports (Howitz et al ., 2003; de Boer et al ., 2006), resveratrol (50 μ M ) stimulated the activity of SIRT1 ∼ 12-fold (Fig. 3). Derivative 1 (3,5-dihydroxy-4'-thiomethyltrans-stilbene), in which the 4'-hydroxyl was replaced with a thiomethyl group, was the most effective, stimulating SIRT1 activity 18-fold, while Derivative 4 (3,5-dihydroxy-4 ′ -methoxytrans -stilbene), bearing a chemically similar methoxy group activated SIRT1 11-fold (Fig. 3). Derivative 2 (3,5-dihydroxy-4'-methyltrans-stilbene) and Derivative 3 (3,5-dihydroxy-4'-ethyltrans-stilbene), substituted with hydrophobic methyl and ethylgroups at the 4' positions, activated SIRT1 16- and 14-fold, respectively. Derivative 5 (3,5-dihydroxy-4'-acetoxytrans-stilbene), bearing an ester group with a relatively large volume at the 4'position was the least potent, stimulating SIRT1 only threefold. Based on this structure–activity relationship, it appears that small, hydrophobic substituents at the 4' position can enhance the potency of stilbenes."

"
The activity of a STAC in vivo will depend on many factors such as its rate of uptake and metabolism. For this reason,
in vitro activity may not always correlate with the ability to activate sirtuins in cells. For example, in vivo esterases are known to readily cleave off acetyl groups from acetyl-containing molecules to release acetate (White & Hope, 1984). For this reason drugs are often acetylated in a prodrug form as a means of enhancing its properties, such as stability, without diminishing its biological activity (Takahashi et al., 1992). Derivative 5, which is acetylated at the 4' position, was the least efficacious of the STACs in activating SIRT1 in vitro, although the lifespan extension it produced was the largest achieved by treatment with a STAC to date, possibly because it remains more stable in the yeast medium than other STACs and is cleaved by esterases once it enters the cell, releasing free resveratrol and acetate and providing a steady
stream of the active compound, but clearly more experiments will be required to confirm this.
"

"



#13 krillin

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Posted 29 April 2008 - 08:49 PM

There is a minor issue with the choice of oil. Olive would be better received than flax. Longer shelf life and not implicated in increased prostate cancer risk. (I admit the studies don't all agree, but there's no need for it if you take fish oil.)

#14 Reverse

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Posted 30 April 2008 - 12:12 AM

There is a minor issue with the choice of oil. Olive would be better received than flax. Longer shelf life and not implicated in increased prostate cancer risk. (I admit the studies don't all agree, but there's no need for it if you take fish oil.)


Yeah, that wasn't set in stone. As soon as I get solid details on what we do I will let you guys know. Again I definitely appreciate all the feedback. Does that price seem fair to everyone?

#15 niner

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Posted 30 April 2008 - 02:34 AM

With this being said triacetyl resveratrol should last longer in the body since the group will either be broken down straight back to the hydroxy version, giving some more time to pass the liver, or the carbonyl group will be converted to a hydroxyl with the side chain intact. I was glad to read in a lot of threads here that people understood that you can not "predict" metabolism, we are talking about millions of enzymes throughout the body many of which we do not understand. One of the reasons we are using a lipophylic delivery system as well is to speed uptake in the intestines. We feel the faster the process the better the chances of high blood levels.

What additions would everyone like to see to this type of product? Quercetin, piperine, HPBC?

Where (or if) it gets broken down depends on the existence of esterases. There are intracellular esterases, so being more lipophilic, it might diffuse into cells more easily, then get cleaved. That would be the ideal situation. I don't know if there are esterases in plasma or not but it would be better in this case if there were not. It is possible to predict metabolism in many cases; that's essentially what an experienced med chemist does, and there are computational models that are somewhat effective. Not perfect though; depends on the case at hand. One question: What is HPBC? HPMC (HydroxyPropyl MethylCellulose) is an agent that we've been talking about recently; B = butyl?

#16 PWAIN

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Posted 30 April 2008 - 04:58 AM

I am not an expert on the chemistry side of this so bear with me please.

I understand that acetylated means that it is attached to a sugar (or something along those lines) to help it be better absorbed/retained?

Other discussions here have talked about using ethanol or other liquid (PEG, Miralax, Tween80 etc) to allow better absorbtion into the body by dissolving the powder. Would it be possible to provide something like this in a capsule form? Most of the suggested liquids are unpleasant to take at best and are really inconvienient, so having something like a capsule form would be excellent.

If the above is possible, what sort of price would we be looking at? I imagine that it may be a bit cheaper than the acetylated stuff, true? I think there would be quite a few takers for such a product, especially if priced right. I would certainly look to switch to such a cap exclusivly if priced right. Perhaps bulk discounts for those of use that normally buy powder?

#17 tintinet

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Posted 30 April 2008 - 03:25 PM

There is a minor issue with the choice of oil. Olive would be better received than flax. Longer shelf life and not implicated in increased prostate cancer risk. (I admit the studies don't all agree, but there's no need for it if you take fish oil.)


Yeah, that wasn't set in stone. As soon as I get solid details on what we do I will let you guys know. Again I definitely appreciate all the feedback. Does that price seem fair to everyone?


I suppose price "fair"-ness might depend upon relative serum levels achieved by acetylated resveratrol vs. the un-acetylated powder or capsules currently available.

#18 Hedgehog

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Posted 30 April 2008 - 03:35 PM

I might be interested but how do you know this won't hurt ppl? Because your changing the chemical structure you could cause it to target other proteins some of which could cause problems over a long period of time.... After tox studies then I might be interested. I just don't think the gain is worth the gamble.
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#19 Reverse

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Posted 30 April 2008 - 03:59 PM

I am not an expert on the chemistry side of this so bear with me please.

I understand that acetylated means that it is attached to a sugar (or something along those lines) to help it be better absorbed/retained?

Other discussions here have talked about using ethanol or other liquid (PEG, Miralax, Tween80 etc) to allow better absorbtion into the body by dissolving the powder. Would it be possible to provide something like this in a capsule form? Most of the suggested liquids are unpleasant to take at best and are really inconvienient, so having something like a capsule form would be excellent.

If the above is possible, what sort of price would we be looking at? I imagine that it may be a bit cheaper than the acetylated stuff, true? I think there would be quite a few takers for such a product, especially if priced right. I would certainly look to switch to such a cap exclusivly if priced right. Perhaps bulk discounts for those of use that normally buy powder?


Actually acetylation is merely attaching acetic acid as a functional group. Sugars are larger and much more complex. As for the liquid question, we are going to have liquid capsules, it will not be a liquid that you will taste. The liquid capsules will be very similar to advil liquidcaps if you have ever taken or seen them before.

#20 inawe

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Posted 30 April 2008 - 05:21 PM

J Agric Food Chem. 2007 Jan 10;55(1):80-9.
Biological activity of acetylated phenolic compounds.Fragopoulou E, Nomikos T, Karantonis HC, Apostolakis C, Pliakis E, Samiotaki M, Panayotou G, Antonopoulou S.
Department of Science of Nutrition--Dietetics, Harokopio University of Athens, 17671 Athens, Greece.

In recent years an effort has been made to isolate and identify biologically active compounds that are included in the Mediterranean diet. The existence of naturally occurring acetylated phenolics, as well as studies with synthetic ones, provide evidence that acetyl groups could be correlated with their biological activity. Platelet activating factor (PAF) is implicated in atherosclerosis, whereas its inhibitors seem to play a protective role against cardiovascular disease. The aim of this study was to examine the biological activity of resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF-induced washed rabbit platelet aggregation. Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC. Acetylated derivatives were identified by negative mass spectrometry. The data showed that tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas diacetylated derivatives induce platelet aggregation. Resveratrol and its mono- and triacetylated derivatives exert similar inhibitory activity, whereas the diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics exert the same or even higher antithrombotic activity compared to the biological activity of the initial one.

PMID: 17199317 [PubMed - indexed for MEDLINE]

#21 Hedgehog

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Posted 30 April 2008 - 05:37 PM

J Agric Food Chem. 2007 Jan 10;55(1):80-9.
Biological activity of acetylated phenolic compounds.Fragopoulou E, Nomikos T, Karantonis HC, Apostolakis C, Pliakis E, Samiotaki M, Panayotou G, Antonopoulou S.
Department of Science of Nutrition--Dietetics, Harokopio University of Athens, 17671 Athens, Greece.

In recent years an effort has been made to isolate and identify biologically active compounds that are included in the Mediterranean diet. The existence of naturally occurring acetylated phenolics, as well as studies with synthetic ones, provide evidence that acetyl groups could be correlated with their biological activity. Platelet activating factor (PAF) is implicated in atherosclerosis, whereas its inhibitors seem to play a protective role against cardiovascular disease. The aim of this study was to examine the biological activity of resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF-induced washed rabbit platelet aggregation. Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC. Acetylated derivatives were identified by negative mass spectrometry. The data showed that tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas diacetylated derivatives induce platelet aggregation. Resveratrol and its mono- and triacetylated derivatives exert similar inhibitory activity, whereas the diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics exert the same or even higher antithrombotic activity compared to the biological activity of the initial one.

PMID: 17199317 [PubMed - indexed for MEDLINE]


Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC.



I don't have the article yet and will post if they found it naturally but it appears that by didn't find it naturally (they performed the acetylation of resveratrol). I think this theory is a great idea. I have no problem with that. I just don't see any evidence that it is safe or not safe IMO.

#22 bixbyte

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Posted 01 May 2008 - 05:33 AM

I first want to say that this forum is quite remarkable. I had never seen it before today and there is a lot of good information on here, not just a bunch of people screaming about things they know nothing about as with a lot of health forums across the internet. Secondly I want to say that I am by no means adverstising this product, I just want to gauge interest in it and I felt like this was a great place to start. I work for a dietary supplement company and we will soon be releasing 3,5,4'-triacetyl resveratrol. It will be in effective dosages (not yet determined) and contain ingredients such as piperine and others to decrease enzymatic activity and increase enzymatic competition. We are toying with the idea of using compounds such as HPBC and flax oil as a delivery system in a liquid capsule. After a lot of research we felt as though this compound was the best of both worlds when it comes to increasing lipophilicity without going as far as creating a trimethoxy compound which in a few studies has shown to have potent anti-tumor properties but negligble antioxidant properties. Would any of you be interested in this sort of product? What would be your concerns? I know one of your main concerns would be price but I can assure you we are not here to rip anyone off or provide a product that contains minute amounts of active ingredients. I have seen this too much in this industry and it is ridiculous. I am not sure of price just yet but it should not exceed $50.



Processing RES into an aspirin like compound?
RES in the presence of Acetic anhydride?

When can I order some?

#23 maxwatt

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Posted 01 May 2008 - 01:12 PM

J Agric Food Chem. 2007 Jan 10;55(1):80-9.
Biological activity of acetylated phenolic compounds.Fragopoulou E, Nomikos T, Karantonis HC, Apostolakis C, Pliakis E, Samiotaki M, Panayotou G, Antonopoulou S.
Department of Science of Nutrition--Dietetics, Harokopio University of Athens, 17671 Athens, Greece.

In recent years an effort has been made to isolate and identify biologically active compounds that are included in the Mediterranean diet. The existence of naturally occurring acetylated phenolics, as well as studies with synthetic ones, provide evidence that acetyl groups could be correlated with their biological activity. Platelet activating factor (PAF) is implicated in atherosclerosis, whereas its inhibitors seem to play a protective role against cardiovascular disease. The aim of this study was to examine the biological activity of resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF-induced washed rabbit platelet aggregation. Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC. Acetylated derivatives were identified by negative mass spectrometry. The data showed that tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas diacetylated derivatives induce platelet aggregation. Resveratrol and its mono- and triacetylated derivatives exert similar inhibitory activity, whereas the diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics exert the same or even higher antithrombotic activity compared to the biological activity of the initial one.

PMID: 17199317 [PubMed - indexed for MEDLINE]


Yaah. There is no reason to believe tri-acetylated resveratrol will or will not have the Sirt1 activating properties of reseratrol. It is equally likely to be damaging as to be beneficial. Since we know what resveratrol does and it can be had in large quantities very reasonably, I believe tri-acetylated resveratrol is not a good bet until more is known about its actual action.

Proteomist synthesized about 10 grams of acetylated resveratrol about a year ago. As far as I know he did not continue in this direction. He hasn't posted since he got his masters and took a "real" job.

Besides the negatives for piperine, there are indications quercetin blocks the action of Sirt1, even though as a sulfonation inhibitor it increases serum levels of resveratrol. Again. possibly good in theory, but not proven and possibly counterproductive.

#24 Reverse

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Posted 01 May 2008 - 03:13 PM

J Agric Food Chem. 2007 Jan 10;55(1):80-9.
Biological activity of acetylated phenolic compounds.Fragopoulou E, Nomikos T, Karantonis HC, Apostolakis C, Pliakis E, Samiotaki M, Panayotou G, Antonopoulou S.
Department of Science of Nutrition--Dietetics, Harokopio University of Athens, 17671 Athens, Greece.

In recent years an effort has been made to isolate and identify biologically active compounds that are included in the Mediterranean diet. The existence of naturally occurring acetylated phenolics, as well as studies with synthetic ones, provide evidence that acetyl groups could be correlated with their biological activity. Platelet activating factor (PAF) is implicated in atherosclerosis, whereas its inhibitors seem to play a protective role against cardiovascular disease. The aim of this study was to examine the biological activity of resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF-induced washed rabbit platelet aggregation. Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC. Acetylated derivatives were identified by negative mass spectrometry. The data showed that tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas diacetylated derivatives induce platelet aggregation. Resveratrol and its mono- and triacetylated derivatives exert similar inhibitory activity, whereas the diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics exert the same or even higher antithrombotic activity compared to the biological activity of the initial one.

PMID: 17199317 [PubMed - indexed for MEDLINE]


Yes, I saw this same study not all that long ago. There are many like it is well that begin to show how acetylated derivatives work better in vivo due to their increased lipophilicity. As with other acetylated derivatives there isn't really anything that would suggest that this would be harmful in any way. There may be no direct studies on the side effects of such an analog, but other very similar derivatives still exhibited potent antioxidant and many other effects.

As for the diacetylation, it is far too expensive to selectively acetylate as opposed to triacetylating. I am a chemist and currently in a doctor of pharmacy program and from what I have seen so far the cost to benefit ratio of diacetylation isn't very good. Again we are just looking to greatly increase lipophilicity, making absorption as quick as possible and delaying break down. We have playing around with the idea of liposomal delivery and we actually had a smaller pharmaceutical company agree to provide their delivery system to it but again the cost was just too high.

#25 Hedgehog

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Posted 01 May 2008 - 03:36 PM

J Agric Food Chem. 2007 Jan 10;55(1):80-9.
Biological activity of acetylated phenolic compounds.Fragopoulou E, Nomikos T, Karantonis HC, Apostolakis C, Pliakis E, Samiotaki M, Panayotou G, Antonopoulou S.
Department of Science of Nutrition--Dietetics, Harokopio University of Athens, 17671 Athens, Greece.

In recent years an effort has been made to isolate and identify biologically active compounds that are included in the Mediterranean diet. The existence of naturally occurring acetylated phenolics, as well as studies with synthetic ones, provide evidence that acetyl groups could be correlated with their biological activity. Platelet activating factor (PAF) is implicated in atherosclerosis, whereas its inhibitors seem to play a protective role against cardiovascular disease. The aim of this study was to examine the biological activity of resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF-induced washed rabbit platelet aggregation. Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC. Acetylated derivatives were identified by negative mass spectrometry. The data showed that tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas diacetylated derivatives induce platelet aggregation. Resveratrol and its mono- and triacetylated derivatives exert similar inhibitory activity, whereas the diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics exert the same or even higher antithrombotic activity compared to the biological activity of the initial one.

PMID: 17199317 [PubMed - indexed for MEDLINE]


Yes, I saw this same study not all that long ago. There are many like it is well that begin to show how acetylated derivatives work better in vivo due to their increased lipophilicity. As with other acetylated derivatives there isn't really anything that would suggest that this would be harmful in any way. There may be no direct studies on the side effects of such an analog, but other very similar derivatives still exhibited potent antioxidant and many other effects.

As for the diacetylation, it is far too expensive to selectively acetylate as opposed to triacetylating. I am a chemist and currently in a doctor of pharmacy program and from what I have seen so far the cost to benefit ratio of diacetylation isn't very good. Again we are just looking to greatly increase lipophilicity, making absorption as quick as possible and delaying break down. We have playing around with the idea of liposomal delivery and we actually had a smaller pharmaceutical company agree to provide their delivery system to it but again the cost was just too high.


Resveratrol is already very lipophillic, if anything you probably want it less lipophillic so it will dissolve into water for example (oil may or may not be a good carrier, it probably causes it to isomerize fast, and one could assume that it would be more attracted to the oil rather then ones cells once you consume it). For it to work you probably would have to show that it activates SIRT1 and doesn't inhibit or activate other proteins. I help run a GMP/FDA chemistry lab and you simply can't make a molecule and start selling it w/o out a lot of work. I don't think you understand the risks involved w/ a new molecule. It takes years for us to get a molecule into the clinic.

#26 Reverse

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Posted 01 May 2008 - 06:49 PM

J Agric Food Chem. 2007 Jan 10;55(1):80-9.
Biological activity of acetylated phenolic compounds.Fragopoulou E, Nomikos T, Karantonis HC, Apostolakis C, Pliakis E, Samiotaki M, Panayotou G, Antonopoulou S.
Department of Science of Nutrition--Dietetics, Harokopio University of Athens, 17671 Athens, Greece.

In recent years an effort has been made to isolate and identify biologically active compounds that are included in the Mediterranean diet. The existence of naturally occurring acetylated phenolics, as well as studies with synthetic ones, provide evidence that acetyl groups could be correlated with their biological activity. Platelet activating factor (PAF) is implicated in atherosclerosis, whereas its inhibitors seem to play a protective role against cardiovascular disease. The aim of this study was to examine the biological activity of resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF-induced washed rabbit platelet aggregation. Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC. Acetylated derivatives were identified by negative mass spectrometry. The data showed that tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas diacetylated derivatives induce platelet aggregation. Resveratrol and its mono- and triacetylated derivatives exert similar inhibitory activity, whereas the diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics exert the same or even higher antithrombotic activity compared to the biological activity of the initial one.

PMID: 17199317 [PubMed - indexed for MEDLINE]


Yes, I saw this same study not all that long ago. There are many like it is well that begin to show how acetylated derivatives work better in vivo due to their increased lipophilicity. As with other acetylated derivatives there isn't really anything that would suggest that this would be harmful in any way. There may be no direct studies on the side effects of such an analog, but other very similar derivatives still exhibited potent antioxidant and many other effects.

As for the diacetylation, it is far too expensive to selectively acetylate as opposed to triacetylating. I am a chemist and currently in a doctor of pharmacy program and from what I have seen so far the cost to benefit ratio of diacetylation isn't very good. Again we are just looking to greatly increase lipophilicity, making absorption as quick as possible and delaying break down. We have playing around with the idea of liposomal delivery and we actually had a smaller pharmaceutical company agree to provide their delivery system to it but again the cost was just too high.


Resveratrol is already very lipophillic, if anything you probably want it less lipophillic so it will dissolve into water for example (oil may or may not be a good carrier, it probably causes it to isomerize fast, and one could assume that it would be more attracted to the oil rather then ones cells once you consume it). For it to work you probably would have to show that it activates SIRT1 and doesn't inhibit or activate other proteins. I help run a GMP/FDA chemistry lab and you simply can't make a molecule and start selling it w/o out a lot of work. I don't think you understand the risks involved w/ a new molecule. It takes years for us to get a molecule into the clinic.



I definitely wouldn't call a hydroxy phenol "very lipophilic" compared to the acetyl phenyls.

Also, everyone needs to be aware that SIRT1 activation is not the only thing one should look for as far as benifits are concerned with resveratrol. I have seen a few of these studies:

http://www.ncbi.nlm....pubmed/15684413

Resveratrol has countless benefits of course, but just be careful what you read. These studies lack standardization and there aren't enough to make a solid claim on a lot of them yet. As for making a new molecule I understand what goes into it and by no means are we stating that anything is FDA approved, considering the length and price it takes. As for changing from a hydroxy to an acetyl there shouldn't be much of a problem at all. The body goes from carbonyl to hydroxy and vice versa all day long. A lot of people underestimate the body and what it can do.

Edited by Reverse, 01 May 2008 - 06:58 PM.


#27 PWAIN

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Posted 02 May 2008 - 12:10 AM

Actually acetylation is merely attaching acetic acid as a functional group. Sugars are larger and much more complex. As for the liquid question, we are going to have liquid capsules, it will not be a liquid that you will taste. The liquid capsules will be very similar to advil liquidcaps if you have ever taken or seen them before.


Acetic acid as found in Vinegar? What would happen if I soaked some ResV in Vinegar? - Probably nothing.

When you say you are going to have liquid capsules, are you also going to have NON actelated resveratrol liquid caps? To be honest, the $60 for 30 x 350 mg caps comes across as a bit high so if I could get 30 x 500mg NON acetelated caps for $30, I'd probably be going for a years supply. Please let me know if you would consider this?

Anyone else here like the idea of non acetlated liquid caps? (for better gut absorbtion)

#28 Ironman

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Posted 03 May 2008 - 04:37 PM

How do you sell this as a supplement since you've tweaked it and now its a drug? Confused....

I think methoxy/methyl/ethyl forms are what SIRTRIS is working on.

#29 Reverse

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Posted 18 May 2008 - 05:03 PM

How do you sell this as a supplement since you've tweaked it and now its a drug? Confused....

I think methoxy/methyl/ethyl forms are what SIRTRIS is working on.


Yes, but just because one company is working with one doesn't mean it is the best for everything. The methoxy form is extremely lipid soluble, making plasma levels rise the fastest. Trimethoxy Resveratrol has been shown to be the most potent anti-tumor analog but the weakest antioxidant form. There are so many benefits of resveratrol that each analog is tailored to a specific need. One of the reasons we chose the triacetyl form is because of the much increased lipid solubility and the fact that we believe ester hydrolysis will convert the acetylated form back to its original form. The faster the absorption and the longer the process the higher the levels of plasma resveratrol levels by prevention/slowing of liver breakdown.

There are many articles that explain the process but a couple for you to see would be:
http://www.ncbi.nlm..../pubmed/9821815
and
http://www.chem.ucal...ch20-3-3-1.html (explains ester hydroloysis)
Posted Image where R' = resveratrol and the O-C=0,-R is the acetyl group.

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

#30 Reverse

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Posted 19 May 2008 - 03:55 PM

How do you sell this as a supplement since you've tweaked it and now its a drug? Confused....

I think methoxy/methyl/ethyl forms are what SIRTRIS is working on.


Yes, but just because one company is working with one doesn't mean it is the best for everything. The methoxy form is extremely lipid soluble, making plasma levels rise the fastest. Trimethoxy Resveratrol has been shown to be the most potent anti-tumor analog but the weakest antioxidant form. There are so many benefits of resveratrol that each analog is tailored to a specific need. One of the reasons we chose the triacetyl form is because of the much increased lipid solubility and the fact that we believe ester hydrolysis will convert the acetylated form back to its original form. The faster the absorption and the longer the process the higher the levels of plasma resveratrol levels by prevention/slowing of liver breakdown.

There are many articles that explain the process but a couple for you to see would be:
http://www.ncbi.nlm..../pubmed/9821815
and
http://www.chem.ucal...ch20-3-3-1.html (explains ester hydroloysis)
Posted Image where R' = resveratrol and the O-C=0,-R is the acetyl group.



I also wanted to add this article as well that shows that acetylated versions are potent antithrombotic inhibitors and are very good for controlling heart disease.

Biological Activity of Acetylated Phenolic Compounds

Elizabeth Fragopoulou, Tzortzis Nomikos, Haralabos C. Karantonis, Constantinos Apostolakis, Emmanuel Pliakis, Martina Samiotaki, George Panayotou, and Smaragdi Antonopoulou*

Department of Science of Nutrition-Dietetics, Harokopio University of Athens, 17671 Athens, Greece, and Protein Chemistry Laboratory B.S.R.C. "Alexander Fleming", Athens, Greece

Received for review September 22, 2006. Revised manuscript received November 6, 2006. Accepted November 8, 2006.

Abstract:

In recent years an effort has been made to isolate and identify biologically active compounds that are included in the Mediterranean diet. The existence of naturally occurring acetylated phenolics, as well as studies with synthetic ones, provide evidence that acetyl groups could be correlated with their biological activity. Platelet activating factor (PAF) is implicated in atherosclerosis, whereas its inhibitors seem to play a protective role against cardiovascular disease. The aim of this study was to examine the biological activity of resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF-induced washed rabbit platelet aggregation. Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC. Acetylated derivatives were identified by negative mass spectrometry. The data showed that tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas diacetylated derivatives induce platelet aggregation. Resveratrol and its mono- and triacetylated derivatives exert similar inhibitory activity, whereas the diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics exert the same or even higher antithrombotic activity compared to the biological activity of the initial one.




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