26 replies to this topic

[manofsan]

And more news from Sirtris on their trials of SRT1720:

http://www.technolog...medicine/21635/

"Resveratrol will pretty soon look like ancient technology," says Sinclair.

Sinclair says that a cousin molecule of SRT1720, which is even more potent, is currently in human trials and will enter clinical studies for the treatment of diseases like type 2 diabetes in 2009. "We could know as early as next year if the same types of benefits we see in mice, we see in humans," he says.

Edited by Mind, 05 November 2008 - 12:08 AM.

[stephen_b]

Wired has an article today on SRT1720, Next-Generation Longevity Drug Works Mouse Wonders.

Stephen

Edit: it's actually a blog posting.

Edited by stephen_b, 04 November 2008 - 11:03 PM.

[malbecman]

They also have the link to the Cell Metabolism article:

http://www.cell.com/...4131(08)00284-2

Nice to see they have Auwerx as the lead author...........

[malbecman]

Just a nice juicy tidbit from the results, still a pretty high dose administered, IMHO.....

"The metabolic actions of SRT1720 were then evaluated by administering the compound by food admixture to wild-type C57BL/6J male mice challenged with a high-fat (HF) diet. The incorporation of the compound to the diet was adjusted weekly to food intake and body weight in order to achieve average exposures of 100 and 500 mg/kg/day (mkd). While the low dose only partially protected from weight gain after not, vert, similar10 weeks of treatment, the high dose totally prevented diet-induced obesity by inhibiting fat accumulation (Figures 2A and 2B). Importantly, this effect on body weight did not result from altered feeding behavior or increased locomotor activity (Figures 2C, 2D, and S2A). Enzymes associated with hepatic injury or tissue breakdown were normal during the study, indicating that SRT1720 was well tolerated and that the efficacy observed was not through a toxic response (Figure S2B)."

[Mind]

Just a quote from the Wired Article:

Mice given the new drug, called SRT1720, gorged on high-fat food for four months without gaining weight or developing diabetes, and ran twice as far on a treadmill as their control-group counterparts. Similar drugs are expected to follow down the pipeline.

"If you look at all the things that have fundamentally changed medicine in the last 150 years, washing hands would be one, and antibiotics another. This could be the third," said study co-author Philip Lambert, a pharmacologist at Sirtris Pharmaceuticals, the drug's developer. "If you could keep your health for another 10 or 15 years, that would be amazing."

SRT1720 activates one of several enzymes that regulate the function of mitochondria — cellular power generators that convert glucose into chemical energy. The wearing down of these generators has been linked to heart disease, Alzheimer's disease, diabetes, cancer and other age-related afflictions.

That same enzyme is also targeted by resveratrol, a naturally occurring compound that reduces age-related diseases in lab animals and is already used by longevity enthusiasts. Researchers at Sirtris showed last year that synthetic drugs that activate the enzyme produced the same cell-level changes as resveratrol, but the tests only lasted for two weeks. The latest study lasted four months, suggesting that SRT1720 — and perhaps the class of enzyme activators expected to follow — are for real.

"This shows you can make drugs that work even better than resveratrol," said David Sinclair, co-founder of Sirtris, who compared the finding to the synthesis of antibiotics inspired by early fungal components. "Now we've got human-designed synthetic molecules. We're not talking about plant extracts anymore."

Rafael de Cabo, a National Institute on Aging gerontologist who is researching SRT1720 but was not involved in the study, published today in Cell Metabolism, agreed with Sinclair's assessment, though he cautioned against premature celebration.

"From rodents to humans is a long, long process," he said. "We've demonstrated this in cells, and in mice. Now we need to move to the next level — primates or humans."

[wydell]

Did we not hear something similar last year regarding mice running twice as long on plain old resveratrol? By the way, it never helped me run any further.

Just a quote from the Wired Article:

Mice given the new drug, called SRT1720, gorged on high-fat food for four months without gaining weight or developing diabetes, and ran twice as far on a treadmill as their control-group counterparts. Similar drugs are expected to follow down the pipeline.

"If you look at all the things that have fundamentally changed medicine in the last 150 years, washing hands would be one, and antibiotics another. This could be the third," said study co-author Philip Lambert, a pharmacologist at Sirtris Pharmaceuticals, the drug's developer. "If you could keep your health for another 10 or 15 years, that would be amazing."

SRT1720 activates one of several enzymes that regulate the function of mitochondria — cellular power generators that convert glucose into chemical energy. The wearing down of these generators has been linked to heart disease, Alzheimer's disease, diabetes, cancer and other age-related afflictions.

That same enzyme is also targeted by resveratrol, a naturally occurring compound that reduces age-related diseases in lab animals and is already used by longevity enthusiasts. Researchers at Sirtris showed last year that synthetic drugs that activate the enzyme produced the same cell-level changes as resveratrol, but the tests only lasted for two weeks. The latest study lasted four months, suggesting that SRT1720 — and perhaps the class of enzyme activators expected to follow — are for real.

"This shows you can make drugs that work even better than resveratrol," said David Sinclair, co-founder of Sirtris, who compared the finding to the synthesis of antibiotics inspired by early fungal components. "Now we've got human-designed synthetic molecules. We're not talking about plant extracts anymore."

Rafael de Cabo, a National Institute on Aging gerontologist who is researching SRT1720 but was not involved in the study, published today in Cell Metabolism, agreed with Sinclair's assessment, though he cautioned against premature celebration.

"From rodents to humans is a long, long process," he said. "We've demonstrated this in cells, and in mice. Now we need to move to the next level — primates or humans."

[Zenob]

A drug designed to specifically hit a protein linked to the life-extending benefits of a meager diet can essentially trick the body into believing food is scarce even when it isn't, suggests a new report in the November Cell Metabolism.

Link

Now we just need to be able to get our hands on some.

[niner]

Did we not hear something similar last year regarding mice running twice as long on plain old resveratrol? By the way, it never helped me run any further.

The dosages that caused mitochodrial biogenesis were on the order of 5g/day for a human, at a minimum, if I recall correctly.

[niner]

Now we just need to be able to get our hands on some.

1720 could take a while; maybe forever. Meanwhile, there's always resveratrol.

[Crepulance]

Have they mentioned how much Res would be needed to match the equivalent benefits of the 1720 trials?


Crep

[tom a]

OK, here's what I don't get. According to Wikipedia, the dose of resveratrol used by Auxwerx in the original study showing greater athletic performance in rats, and showing comparable results to those now found for 1720, was 400mg/kg/day.

Supposedly, 1720 is many, many times more potent. Yet the 100mg/kg/day dose did NOT provide the full benefits found in either the 500mg/kg/day dose of 1720, or, it would seem, in the 400mg/kg/day dose of resveratrol.

So what is the real advantage of 1720?

What am I missing here?

Edited by tom a, 05 November 2008 - 01:41 PM.

[stephen_b]

So what is the real advantage of 1720?

What am I missing here?

Well ...

"Now we've got human-designed synthetic molecules. We're not talking about plant extracts anymore."

There's one huge difference: Sitris can patent SRT1720 and make a lot of $$$. For plant extracts, there's Shaklee.


(Wow, aren't I pessimistic this morning; there's posting while drunk and in my case posting before coffee )

StephenB

Edited by stephen_b, 05 November 2008 - 01:53 PM.

[malbecman]

While the improvement in athletic performance is noted in this paper, I believe the main point is that the mice on a HF diet and the high dose of 1720 showed *no* weight gain. That's pretty remarkable and likely cannot be seen w/ straight resveratrol.

OK, here's what I don't get. According to Wikipedia, the dose of resveratrol used by Auxwerx in the original study showing greater athletic performance in rats, and showing comparable results to those now found for 1720, was 400mg/kg/day.

Supposedly, 1720 is many, many times more potent. Yet the 100mg/kg/day dose did NOT provide the full benefits found in either the 500mg/kg/day dose of 1720, or, it would seem, in the 400mg/kg/day dose of resveratrol.

So what is the real advantage of 1720?

What am I missing here?

Edited by malbecman, 05 November 2008 - 06:21 PM.

[Ringostarr]

Here is the deal - the results with the 1720 drug are exactly the same as with the resveratrol (and in the similar dosages!). Glaxo can't make money on resveratrol (because it is not patentable) so they are downplaying its effectiveness. This French scientist who conducted the study works for Sirtris/Glaxo to boot. That being said, the bottom line as I see it, someone could take 500 mg to 1000 mg of micronized resveratrol per day at one tenth of the cost Glaxo is talking about ($7 dollars per pill) and get the same benefits (and without the doctor's visits). I am not downplaying how exciting these sythetic molecules are but the case has not been made for why ther are necessary. The potency argument does not add up as you stated. Also, the mice taking in 400 mg/kg/day of resveratrol per day did lose weight. In sum, be prepared for futher assaults on resveratrol by Glaxo. They have to make their case as to why they spent $720 million in shareholder money for Sirtris. These attacks are now coming from $$David Sinclair$$ who JUST a month ago seemingly endorsed a dietary supplement resveratrol product. My guess is that Glaxo either came down on him very hard or paid him more money to go on the assault and quit touting resveratrol.

While the improvement in athletic performance is noted in this paper, I believe the main point is that the mice on a HF diet and the high dose of 1720 showed *no* weight gain. That's pretty remarkable and likely cannot be seen w/ straight resveratrol.

OK, here's what I don't get. According to Wikipedia, the dose of resveratrol used by Auxwerx in the original study showing greater athletic performance in rats, and showing comparable results to those now found for 1720, was 400mg/kg/day.

Supposedly, 1720 is many, many times more potent. Yet the 100mg/kg/day dose did NOT provide the full benefits found in either the 500mg/kg/day dose of 1720, or, it would seem, in the 400mg/kg/day dose of resveratrol.

So what is the real advantage of 1720?

What am I missing here?

[Crepulance]

Yeah but, taking 500mg to 1000mg of Res doesn't make you not gain wait when eating fattening food. Right? Or has someone taking that dosage experienced that craziness? If they have speak up, cause I'm not taking that much. That's obviously the anomoly between the two, so if you are gaining wait with just high dose res, then that's why 1720 is better.



Crep

[getmarkus]

This really caught my eye...

The last paragraph in the article where it says,

"Sinclair says that a cousin molecule of SRT1720, which is even more potent, is currently in human trials and will enter clinical studies for the treatment of diseases like type 2 diabetes in 2009."

I am pretty certain they are referring to SRT2104 another NCE (New Chemical Entity) created by Sirtris and which is currently in "first-in-human" Phase 1a trials. This is supposed to be even more potent then SRT1720. While I understand Sirtris needs a marketable product and they may have other motives for designing these drugs, you have to give them credit for all the potentially ground-breaking work they are doing.

In an article recently written on xconomy.com a journalist interviewed Westphal and I was impressed by one of the quotes he made.

"I think ultimately, from a pharmaceutical- company perspective, a patented, composition-of-matter compound that is 1,000 times more potent is going to be more attractive than reformulated resveratrol, so definitely our focus is more on the NCEs," Westphal says.

My interpretation was he owned up to the fact that SRT501 is in fact something they will have trouble monetizing. He also said that SRT501 trials in Diabetes will be "scrapped" but will continue on in MELAS and and Colon Cancer.

A direct like to the article can be found here: Sirtris' Red Wine Chemical to Take Back Seat to "Potent" Diabetes Drugs

My review of the article and a link to the original piece can be found here: Sirtris Makes Major Moves - Goes Relatively Unreported!

I found Westphal to be very candid with regards to the plan for his existing and future prospects within Sirtris. The article itself is a great short read.

Cheers,
Markus

Edited by getmarkus, 07 November 2008 - 04:10 AM.

[Ringostarr]

Here is what I have issue with:
Sirtris downplays the effectiveness of resveratrol. It's twisted press releases and reported studies make it seem like one has to mega dose to greatly benefit from resveratrol. This is just not so. EVERY resveratrol study I have read,(not conducted by Sirtis) reveals that the effective dose of resveratrol is much smaller than they are reporting. For humans I belive it is between 300 and 500 mg per day for health maintenance. And $Sinclair$ knows this. He has been brainwashed or pressured by Glaxo/Westphal to fall in line. This is to the detriment of millions of people who are now confused about dosages, effectivenss etc. becaues of the conflicting and confusing reports released by the Sirtris machine. I do not say "machine" without reason. Most of the major resveratrol scientists are now on the Sirtris payroll. They are not reporting on the benefits of resveratrol anymore. They are not publishing experiments. They are focused on the NCE's when, quite frankly, I'm not even sure they are needed? - especially for health maintenance, especially considering 500 mg per day is a VERY attainable amount. I know Sirtris is not in the business of public servitude, but they are intentionally misleading people. I know what is going on and am concerned.

This really caught my eye...

The last paragraph in the article where it says,

"Sinclair says that a cousin molecule of SRT1720, which is even more potent, is currently in human trials and will enter clinical studies for the treatment of diseases like type 2 diabetes in 2009."

I am pretty certain they are referring to SRT2104 another NCE (New Chemical Entity) created by Sirtris and which is currently in "first-in-human" Phase 1a trials. This is supposed to be even more potent then SRT1720. While I understand Sirtris needs a marketable product and they may have other motives for designing these drugs, you have to give them credit for all the potentially ground-breaking work they are doing.

In an article recently written on xconomy.com a journalist interviewed Westphal and I was impressed by one of the quotes he made.

"I think ultimately, from a pharmaceutical- company perspective, a patented, composition-of-matter compound that is 1,000 times more potent is going to be more attractive than reformulated resveratrol, so definitely our focus is more on the NCEs," Westphal says.

My interpretation was he owned up to the fact that SRT501 is in fact something they will have trouble monetizing. He also said that SRT501 trials in Diabetes will be "scrapped" but will continue on in MELAS and and Colon Cancer.

A direct like to the article can be found here: Sirtris' Red Wine Chemical to Take Back Seat to "Potent" Diabetes Drugs

My review of the article and a link to the original piece can be found here: Sirtris Makes Major Moves - Goes Relatively Unreported!

I found Westphal to be very candid with regards to the plan for his existing and future prospects within Sirtris. The article itself is a great short read.

Cheers,
Markus

[getmarkus]

At this point with the lack of human studies that have been completed over lengthy periods of time I don't think anyone can say "for sure" what is the most effective way to take resveratrol, or these new NCE's. Perhaps larger doeses are needed, perhaps they are not. Sirtris does not seem to be focused on "health maintenance," rather trying to cure serious diseases related to aging. I have no problems with companies who are attempting to solve major problems, making lots of money for doing it. As of now they aren't making any.

Your take on Sirtris may be correct but I am hopeful the outcome of their research will be greater then the potential misconduct you are suggesting.

Here is what I have issue with:
Sirtris downplays the effectiveness of resveratrol. It's twisted press releases and reported studies make it seem like one has to mega dose to greatly benefit from resveratrol. This is just not so. EVERY resveratrol study I have read,(not conducted by Sirtis) reveals that the effective dose of resveratrol is much smaller than they are reporting. For humans I belive it is between 300 and 500 mg per day for health maintenance. And $Sinclair$ knows this. He has been brainwashed or pressured by Glaxo/Westphal to fall in line. This is to the detriment of millions of people who are now confused about dosages, effectivenss etc. becaues of the conflicting and confusing reports released by the Sirtris machine. I do not say "machine" without reason. Most of the major resveratrol scientists are now on the Sirtris payroll. They are not reporting on the benefits of resveratrol anymore. They are not publishing experiments. They are focused on the NCE's when, quite frankly, I'm not even sure they are needed? - especially for health maintenance, especially considering 500 mg per day is a VERY attainable amount. I know Sirtris is not in the business of public servitude, but they are intentionally misleading people. I know what is going on and am concerned.

This really caught my eye...

The last paragraph in the article where it says,

"Sinclair says that a cousin molecule of SRT1720, which is even more potent, is currently in human trials and will enter clinical studies for the treatment of diseases like type 2 diabetes in 2009."

I am pretty certain they are referring to SRT2104 another NCE (New Chemical Entity) created by Sirtris and which is currently in "first-in-human" Phase 1a trials. This is supposed to be even more potent then SRT1720. While I understand Sirtris needs a marketable product and they may have other motives for designing these drugs, you have to give them credit for all the potentially ground-breaking work they are doing.

In an article recently written on xconomy.com a journalist interviewed Westphal and I was impressed by one of the quotes he made.

"I think ultimately, from a pharmaceutical- company perspective, a patented, composition-of-matter compound that is 1,000 times more potent is going to be more attractive than reformulated resveratrol, so definitely our focus is more on the NCEs," Westphal says.

My interpretation was he owned up to the fact that SRT501 is in fact something they will have trouble monetizing. He also said that SRT501 trials in Diabetes will be "scrapped" but will continue on in MELAS and and Colon Cancer.

A direct like to the article can be found here: Sirtris' Red Wine Chemical to Take Back Seat to "Potent" Diabetes Drugs

My review of the article and a link to the original piece can be found here: Sirtris Makes Major Moves - Goes Relatively Unreported!

I found Westphal to be very candid with regards to the plan for his existing and future prospects within Sirtris. The article itself is a great short read.

Cheers,
Markus

[Ringostarr]

When I say health maintainance, I mean figting the diseases of ageing (i.e. not getting diseases such as cancer, Alzheimer's etc. and thus living longer). Also, I would not say what Sirtris is doing is misconduct from a business standpoint. They just arn't telling the whole story. They are intentionally leaving the lower dosage resveratrol trials out. Every trial reports on 2 to 5 grams of resveratrol consumed; they have intentionally set the bar very high (and have avoided publishing the lower dosage studies). It is a way to make readers and the media believe that resveratrol is not that powerful and a way to suggest that their proprietary drugs were the solution. Very clever.

Eventually (even though Sirtis has hired many of the resveratrol scientists) studies from other scientists will prove once and for all that a lower does is effective for humans (this has already happened in mice - the effective human equivalent to replicate caloric restriction is around 400 mg per day as opposed to 2 grams per day - all things being equal). All the while, this is giving Sirtris a time cushion. The more Sirtis can stall the widespread adoption of resveratrol, the better it will be able to postion it's drugs that are not available because they have to pass FDA approval. All the while, the message is not getting out to the gernaral population. All the while, people are missing the benefits of resveratrol. Have you noticed how Sirtris is NOW saying you would have to drink a few gallons of wine to get the benefits of resveratrol - it used to be (not less than a year ago) 1000 bottles was what it would take. They realized what they were saying was not true - they have drasticlly lowered the required effective dosage as seen by this. All of this is very choreographed.
Cheers, Ringo

At this point with the lack of human studies that have been completed over lengthy periods of time I don't think anyone can say "for sure" what is the most effective way to take resveratrol, or these new NCE's. Perhaps larger doeses are needed, perhaps they are not. Sirtris does not seem to be focused on "health maintenance," rather trying to cure serious diseases related to aging. I have no problems with companies who are attempting to solve major problems, making lots of money for doing it. As of now they aren't making any.

Your take on Sirtris may be correct but I am hopeful the outcome of their research will be greater then the potential misconduct you are suggesting.

Here is what I have issue with:
Sirtris downplays the effectiveness of resveratrol. It's twisted press releases and reported studies make it seem like one has to mega dose to greatly benefit from resveratrol. This is just not so. EVERY resveratrol study I have read,(not conducted by Sirtis) reveals that the effective dose of resveratrol is much smaller than they are reporting. For humans I belive it is between 300 and 500 mg per day for health maintenance. And $Sinclair$ knows this. He has been brainwashed or pressured by Glaxo/Westphal to fall in line. This is to the detriment of millions of people who are now confused about dosages, effectivenss etc. becaues of the conflicting and confusing reports released by the Sirtris machine. I do not say "machine" without reason. Most of the major resveratrol scientists are now on the Sirtris payroll. They are not reporting on the benefits of resveratrol anymore. They are not publishing experiments. They are focused on the NCE's when, quite frankly, I'm not even sure they are needed? - especially for health maintenance, especially considering 500 mg per day is a VERY attainable amount. I know Sirtris is not in the business of public servitude, but they are intentionally misleading people. I know what is going on and am concerned.

This really caught my eye...

The last paragraph in the article where it says,

"Sinclair says that a cousin molecule of SRT1720, which is even more potent, is currently in human trials and will enter clinical studies for the treatment of diseases like type 2 diabetes in 2009."

I am pretty certain they are referring to SRT2104 another NCE (New Chemical Entity) created by Sirtris and which is currently in "first-in-human" Phase 1a trials. This is supposed to be even more potent then SRT1720. While I understand Sirtris needs a marketable product and they may have other motives for designing these drugs, you have to give them credit for all the potentially ground-breaking work they are doing.

In an article recently written on xconomy.com a journalist interviewed Westphal and I was impressed by one of the quotes he made.

"I think ultimately, from a pharmaceutical- company perspective, a patented, composition-of-matter compound that is 1,000 times more potent is going to be more attractive than reformulated resveratrol, so definitely our focus is more on the NCEs," Westphal says.

My interpretation was he owned up to the fact that SRT501 is in fact something they will have trouble monetizing. He also said that SRT501 trials in Diabetes will be "scrapped" but will continue on in MELAS and and Colon Cancer.

A direct like to the article can be found here: Sirtris' Red Wine Chemical to Take Back Seat to "Potent" Diabetes Drugs

My review of the article and a link to the original piece can be found here: Sirtris Makes Major Moves - Goes Relatively Unreported!

I found Westphal to be very candid with regards to the plan for his existing and future prospects within Sirtris. The article itself is a great short read.

Cheers,
Markus

[maxwatt]

When I say health maintainance, I mean figting the diseases of ageing (i.e. not getting diseases such as cancer, Alzheimer's etc. and thus living longer). Also, I would not say what Sirtris is doing is misconduct from a business standpoint. They just arn't telling the whole story. They are intentionally leaving the lower dosage resveratrol trials out. Every trial reports on 2 to 5 grams of resveratrol consumed; they have intentionally set the bar very high (and have avoided publishing the lower dosage studies). It is a way to make readers and the media believe that resveratrol is not that powerful and a way to suggest that their proprietary drugs were the solution. Very clever.

Eventually (even though Sirtis has hired many of the resveratrol scientists) studies from other scientists will prove once and for all that a lower does is effective for humans (this has already happened in mice - the effective human equivalent to replicate caloric restriction is around 400 mg per day as opposed to 2 grams per day - all things being equal). All the while, this is giving Sirtris a time cushion. The more Sirtis can stall the widespread adoption of resveratrol, the better it will be able to postion it's drugs that are not available because they have to pass FDA approval. All the while, the message is not getting out to the gernaral population. All the while, people are missing the benefits of resveratrol. Have you noticed how Sirtris is NOW saying you would have to drink a few gallons of wine to get the benefits of resveratrol - it used to be (not less than a year ago) 1000 bottles was what it would take. They realized what they were saying was not true - they have drasticlly lowered the required effective dosage as seen by this. All of this is very choreographed.
Cheers, Ringo

The problem is that all other things are not equal between mice and men. Humans have far more effective enzymes for metabolizing phytochemicals than do mice. This was discussed in the thread on maximizing resveratrol effectiveness over a year ago. To summarize the conclusions, humans need much higher equivalent doses than do rodents. Moreover, human cytochrome enzymes differ such that certain ethnic groups, such as east Asians, would need less resveratrol than Caucasians to achieve similar blood serum levels. Sirtris did publish some studies at 2.5 grams rather than 5 grams in their diabetes study. 2.5 grams did have an effect, but less than 5 grams.

While under-a- gram doses may have some beneficial effects, it won't be enough to activate sirtuin genes and get those beneficial effects.

The graphs I've seen on sirtuin activation by Sirtris' proprietary compounds, indicates that while they preferentially activate Sirt1, they are no more effective than resveratrol at activating Sirt2 through Sirt7. But for treating specific diseases caused by Sirt1 dysfunction, the compounds could be beneficial. For general life-extension, not so much I think. But relatively high doses will be needed.

[Crepulance]

Gang, can anyone answer my original question, which was how much res would you have to take to mimic the result achieved by the fat fed mice who didn't gain any weight after four months? And has anyone personally experienced these results?


Crep

When I say health maintainance, I mean figting the diseases of ageing (i.e. not getting diseases such as cancer, Alzheimer's etc. and thus living longer). Also, I would not say what Sirtris is doing is misconduct from a business standpoint. They just arn't telling the whole story. They are intentionally leaving the lower dosage resveratrol trials out. Every trial reports on 2 to 5 grams of resveratrol consumed; they have intentionally set the bar very high (and have avoided publishing the lower dosage studies). It is a way to make readers and the media believe that resveratrol is not that powerful and a way to suggest that their proprietary drugs were the solution. Very clever.

Eventually (even though Sirtis has hired many of the resveratrol scientists) studies from other scientists will prove once and for all that a lower does is effective for humans (this has already happened in mice - the effective human equivalent to replicate caloric restriction is around 400 mg per day as opposed to 2 grams per day - all things being equal). All the while, this is giving Sirtris a time cushion. The more Sirtis can stall the widespread adoption of resveratrol, the better it will be able to postion it's drugs that are not available because they have to pass FDA approval. All the while, the message is not getting out to the gernaral population. All the while, people are missing the benefits of resveratrol. Have you noticed how Sirtris is NOW saying you would have to drink a few gallons of wine to get the benefits of resveratrol - it used to be (not less than a year ago) 1000 bottles was what it would take. They realized what they were saying was not true - they have drasticlly lowered the required effective dosage as seen by this. All of this is very choreographed.
Cheers, Ringo

The problem is that all other things are not equal between mice and men. Humans have far more effective enzymes for metabolizing phytochemicals than do mice. This was discussed in the thread on maximizing resveratrol effectiveness over a year ago. To summarize the conclusions, humans need much higher equivalent doses than do rodents. Moreover, human cytochrome enzymes differ such that certain ethnic groups, such as east Asians, would need less resveratrol than Caucasians to achieve similar blood serum levels. Sirtris did publish some studies at 2.5 grams rather than 5 grams in their diabetes study. 2.5 grams did have an effect, but less than 5 grams.

While under-a- gram doses may have some beneficial effects, it won't be enough to activate sirtuin genes and get those beneficial effects.

The graphs I've seen on sirtuin activation by Sirtris' proprietary compounds, indicates that while they preferentially activate Sirt1, they are no more effective than resveratrol at activating Sirt2 through Sirt7. But for treating specific diseases caused by Sirt1 dysfunction, the compounds could be beneficial. For general life-extension, not so much I think. But relatively high doses will be needed.

[Smith]

Yeah but, taking 500mg to 1000mg of Res doesn't make you not gain wait when eating fattening food. Right? Or has someone taking that dosage experienced that craziness? If they have speak up, cause I'm not taking that much. That's obviously the anomoly between the two, so if you are gaining wait with just high dose res, then that's why 1720 is better.

I've been taking a daily 500mg dosage of Resv for almost 12 months now. For the first 8 months of this year, I had a very vigourous daily workout regimin, and my body fat percentage was consistently around 10%. Due to a change in jobs in September 2008 and the fact I now have a 4 hour commute, I am no longer able to workout anymore until next year. Without any dietary changes, I've seen my body fat go from 10% to almost 16% while on 500mg of daily RESV. So I seriously doubt that RESV alone (at least 500mg daily) can prevent you from gaining fat.

[stephen_b]

[nevermind]

Edited by stephen_b, 17 November 2008 - 06:17 PM.

[maxwatt]

Yeah but, taking 500mg to 1000mg of Res doesn't make you not gain wait when eating fattening food. Right? Or has someone taking that dosage experienced that craziness? If they have speak up, cause I'm not taking that much. That's obviously the anomoly between the two, so if you are gaining wait with just high dose res, then that's why 1720 is better.

I've been taking a daily 500mg dosage of Resv for almost 12 months now. For the first 8 months of this year, I had a very vigourous daily workout regimin, and my body fat percentage was consistently around 10%. Due to a change in jobs in September 2008 and the fact I now have a 4 hour commute, I am no longer able to workout anymore until next year. Without any dietary changes, I've seen my body fat go from 10% to almost 16% while on 500mg of daily RESV. So I seriously doubt that RESV alone (at least 500mg daily) can prevent you from gaining fat.

This is a useful data point to have. I have found when I cannot burn my usual extra 1000 calories a day, I must consciously reduce my calorie intake to avoid weight gain, even taking five times your dose. This is consistent with Sinclair's paper two years ago; the high-fat diet mice on reseratrol did gain weight, though not as much as those without resveratrol. ut more significantly, the resveratrol high-fat diet mice did not develop degenerative diseases.

[malbecman]

I can chime in on the noted weight gain as well at my usual doseage of ~1-2 grams daily. When my caloric intakes increases or exercise decreases for one reason or another, I have seen my weight begin to creep up. That said, I do also think my athletic performance for a 41 yr old is now well above average when compared to my peers.

Yeah but, taking 500mg to 1000mg of Res doesn't make you not gain wait when eating fattening food. Right? Or has someone taking that dosage experienced that craziness? If they have speak up, cause I'm not taking that much. That's obviously the anomoly between the two, so if you are gaining wait with just high dose res, then that's why 1720 is better.

I've been taking a daily 500mg dosage of Resv for almost 12 months now. For the first 8 months of this year, I had a very vigourous daily workout regimin, and my body fat percentage was consistently around 10%. Due to a change in jobs in September 2008 and the fact I now have a 4 hour commute, I am no longer able to workout anymore until next year. Without any dietary changes, I've seen my body fat go from 10% to almost 16% while on 500mg of daily RESV. So I seriously doubt that RESV alone (at least 500mg daily) can prevent you from gaining fat.

This is a useful data point to have. I have found when I cannot burn my usual extra 1000 calories a day, I must consciously reduce my calorie intake to avoid weight gain, even taking five times your dose. This is consistent with Sinclair's paper two years ago; the high-fat diet mice on reseratrol did gain weight, though not as much as those without resveratrol. ut more significantly, the resveratrol high-fat diet mice did not develop degenerative diseases.

[kenj]

Taking resveratrol in quite an intermittent fashion, and IME it's always more difficult to restrict calories while on resveratrol, and thus I've gained a few pounds (other stuff like mild CR, exercises, etc. contribute to a lower bodyweight than in my teens, though). ISTM my blood sugar is lower when I take resveratrol.

[Crepulance]

When's the soonest you think it's possible this might be out? Also do you know where to go to try and sign up for the clinical trial?


Crep

Taking resveratrol in quite an intermittent fashion, and IME it's always more difficult to restrict calories while on resveratrol, and thus I've gained a few pounds (other stuff like mild CR, exercises, etc. contribute to a lower bodyweight than in my teens, though). ISTM my blood sugar is lower when I take resveratrol.