19 replies to this topic

[Crepulance]

Gentlemen. Evaluate. Comment.



Plain Mega-Dose Resveratrol Fails To Mimic Metabolic Effects Of Calorie Restriction
Has The Idea Of A Red-Wine Resveratrol Pill, That Mimics A Calorie-Restricted Diet, Fizzled?

In a surprising mouse study conducted by researchers at Williams College (Williamstown, Mass), researchers report that resveratrol (rez-vair-ah-trawl), widely known as a red wine molecule and purported to be a molecular mimic of a restricted calorie diet, failed to produce the characteristic metabolic effects commonly observed in animals given a limited-calorie diet.

Animals placed on mega-dose resveratrol (4200-7070 mg equivalent for a 160-lb human) did not reduce body temperature or slow the heart rate, effects which are commonly observed among calorie-restricted animals.

Another less publicized study published last year also showed resveratrol did not slow heart rate. The heart rate in mice fed a standard-calorie diet was 342 beats per minute vs 360 beats per minute for resveratrol-fed mice. [Biology Trace Element Research 2007 118:250–254]

Furthermore, in striking opposition to a previous trial, Williams College researchers found mega-dose resveratrol actually reduced physical endurance in a mouse treadmill test.

The study, published in an advanced online edition of The FASEB Journal (Fellowship of Experimental Biology & Medicine, Dec, 4, 2008), follows a report issued in August of 2008 showing animals on a standard-calorie diet given mega-dose plain resveratrol (360-1565 milligrams) did not live as long as mice who were not given resveratrol. In fact, as the dose of resveratrol increased, lifespan decreased. [Cell Metabolism 2008 August; 8(2): 157–168]

The mice in this August 2008 study did exhibit profound improvements in health, including prevention of cataracts, reduced inflammation and greater motor nerve coordination. But the failure to prolong life was a setback to the idea of mega-dose resveratrol as an anti-aging pill. [Cell Metabolism 2008 August; 8(2): 157–168]

A growing body of data appears to be pointing towards lower-dose resveratrol and synergistic biological action when resveratrol is accompanied by an array of other natural molecules, similar in dosage to the amount of polyphenolic molecules provided in 3-to-5 glasses of dark red wine.

In June 2008 University of Wisconsin researchers reported relatively low dose resveratrol (a human equivalent dose of 343 mg) closely mimics the global gene activation profile of calorie restriction. [PLoS ONE 2008 3(6): e2264] Calorie restriction unequivocally prolongs the life of all life forms, approximately doubling the lifespan by cutting caloric intake in half.

Then in September of 2008 the same researchers reported that a patented array of nutriceuticals (Longevinex®), which included resveratrol, quercetin and rice bran phytate IP6, significantly affected 9-times more genes (1711 gene) than calorie restriction (198 genes) or plain resveratrol (225 genes) at a dose of resveratrol (100 mg resveratrol human equivalent) that was 17-320 times lower than prior studies. Longevinex® provides a total of 250 mg of mineral-chelating (key-lay-ting) molecules, about what is provided in 3-5 glasses of dark red wine. Red wine drinking populations in France and Sardinia are known to exhibit unusual longevity despite their high-calorie diets.

A plethora of mega-dose resveratrol dietary supplements came onto the market in 2006 following a study showing mega-dose resveratrol (1565 mg) did indeed increase the lifespan of mice. But the mice were engorged with a supra-high fat calorie diet (~60% fat calories) which is far greater than a typical human diet (~30% fat calories), so it is not applicable to the human condition. [Nature. 2006 Nov 16; 444 (7117):337-42] News reports at the time claimed only mega-dose resveratrol would be effective, based upon statements by an Ivy League university professor who was touting a resveratrol-based, gene activating drug at the time.

For more authoritative information about resveratrol and red wine pills, you are invited to visit www.longevinex.com #### Copyright 2008 Resveratrol Partners LLC Not for posting on other websites. .


--------------------------------------------------------------------------------

Abstract

FASEB Journal 2008 Dec 4. [Epub ahead of print]

Resveratrol treatment in mice does not elicit the bradycardia and hypothermia associated with calorie restriction.
Mayers JR, Iliff BW, Swoap SJ.

*Department of Biology, Williams College, Williamstown, Massachusetts, USA.

Dietary supplementation with resveratrol may produce calorie restriction-like effects on metabolic and longevity endpoints in mice. In this study, we sought to determine whether resveratrol treatment elicited other hallmark changes associated with calorie restriction, namely bradycardia and decreased body temperature. We found that during short-term treatment, wild-type mice on a calorie-restricted diet experienced significant decreases in both heart rate and body temperature after only 1 day whereas those receiving resveratrol exhibited no such change after 1 wk. We also used ob/ob mice to study the effects of long-term treatment because previous studies had indicated the therapeutic value of resveratrol against the linked morbidities of obesity and diabetes. After 12 wk, resveratrol treatment had produced no changes in either heart rate or body temperature. Strikingly, and in contrast to previous findings, we found that resveratrol-treated mice had significantly reduced endurance in a treadmill test. Quantitative reverse transcriptase-polymerase chain reaction suggested that a proposed target of resveratrol, Sirt1, was activated in resveratrol-treated ob/ob mice. Thus, we conclude that the bradycardia and hypothermia associated with calorie restriction occur through mechanisms unaffected by the actions of resveratrol and that further studies are needed to examine the differential effects of resveratrol in a leptin-deficient background.-Mayers, J. R., Iliff, B. W., Swoap, S. J. Resveratrol treatment in mice does not elicit the bradycardia and hypothermia associated with calorie restriction.

©Copyright 2008 Resveratrol Partners LLC Not for posting on other websites.

[PWAIN]

Crepulance

Save us all the wasted time by stating at the beginning that this is a twisted Longivinex infomercial.

This company is selective and mis representative at best so why would anyone want to waste time chasing up their articles.

[suspire]

Crepulance

Save us all the wasted time by stating at the beginning that this is a twisted Longivinex infomercial.

This company is selective and mis representative at best so why would anyone want to waste time chasing up their articles.

I agree that the article reads like a Longevinex press release, but could you explain your own statements in further detail? Why are they mis-representative? Is the information in the article incorrect? I am sure it'd be helpful for the larger audience who isn't quite as focused on these debates/discussions. I'll admit, I also read that article (while searching for info on IP6) and wondered what exactly it implied/meant versus other forms of resveratrol on the market.

Edited by suspire, 11 December 2008 - 11:18 PM.

[PWAIN]

Crepulance

Save us all the wasted time by stating at the beginning that this is a twisted Longivinex infomercial.

This company is selective and mis representative at best so why would anyone want to waste time chasing up their articles.

I agree that the article reads like a Longevinex press release, but could you explain your own statements in further detail? Why are they mis-representative? Is the information in the article incorrect? I am sure it'd be helpful for the larger audience who isn't quite as focused on these debates/discussions. I'll admit, I also read that article (while searching for info on IP6) and wondered what exactly it implied/meant versus other forms of resveratrol on the market.

Small example of inaccuracy:

250 mg of mineral-chelating (key-lay-ting) molecules, about what is provided in 3-5 glasses of dark red wine

Thats between 50mg and 83mg per glass. But that is not the main point I was making.

The article is one sided ie. it doesn't provide a balanced presentation of the current evidence. They therefore mis represent the current view of the scientific community. Their evidence in not invalid, but it is only part of the picture and therefore mis representative.

New evidence is coming in that water is able to kill, avoid at all costs. Inaccurate? No. Mis representative? ______

You decide.

[Anthony_Loera]

Resvhead,

This was copied was directly from a Longevinex email blast, made about 17 hours ago...

Cheers
A

Edited by Anthony_Loera, 11 December 2008 - 11:12 PM.

[suspire]

Crepulance

Save us all the wasted time by stating at the beginning that this is a twisted Longivinex infomercial.

This company is selective and mis representative at best so why would anyone want to waste time chasing up their articles.

I agree that the article reads like a Longevinex press release, but could you explain your own statements in further detail? Why are they mis-representative? Is the information in the article incorrect? I am sure it'd be helpful for the larger audience who isn't quite as focused on these debates/discussions. I'll admit, I also read that article (while searching for info on IP6) and wondered what exactly it implied/meant versus other forms of resveratrol on the market.

Small example of inaccuracy:

250 mg of mineral-chelating (key-lay-ting) molecules, about what is provided in 3-5 glasses of dark red wine

Thats between 50mg and 83mg per glass. But that is not the main point I was making.

The article is one sided ie. it doesn't provide a balanced presentation of the current evidence. They therefore mis represent the current view of the scientific community. Their evidence in not invalid, but it is only part of the picture and therefore mis representative.

New evidence is coming in that water is able to kill, avoid at all costs. Inaccurate? No. Mis representative? ______

You decide.

Fair enough. And Crep has a habit of posting some, uh, dubious stuff. That said, are you saying that basic premise of the pr release is incorrect? That mega-dosing study is incorrect? As for some of the other claims, yeah, I am fairly skeptical. For instance, the whole " significantly affected 9-times more genes"--that seems to me to be because they have Vitamin D, quercetin and IP6 in their formula, not because their resveratrol or their delivery system is somehow superior. If I am wrong about this--and someone else knows more about it than I--please do speak up! But when I read that part, it made me think: Well, sure. If you add X, Y and Z into your formula, it will do other things. But we could just take reservatrol for one supplier, and add quercetin and IP6 to it if we wanted to." But once again, I am unsure where the truth is in all of this stuff.

Still, the focus of the article, the mega-dosing bit, I'd like to hear if people actually think that's incorrect, if the study is somehow flawed or what have you.

[geddarkstorm]

Firstly, the average mouse heart rate is between 500-600 bpm, never down in the 300s. So immediately this totally throws a wrench in such data.

Secondly, that paper about heart rate and body temperature that just came out used ob/ob mice, which are genetically messed up to be leptin deficient. Leptin is a hormone that is highly important for metabolism regulation; it also regulates immune response, plays a role in vascular growth, and mice without it are infertile. The response of ob/ob mice to resveratrol, especially their loss of endurance, is impossible to compare to wildtype mice and humans - ob/ob mice are really screwed up mice. Additionally, I can't find where they say what amount of resveratrol they used, though regrettably I can only see their abstract. Saying "human equivalent dose" means nothing, as we have no idea how it was calculated. PMID: 19056839

Thirdly, 400mg/kg resveratrol in mice has been show to lower resting heart rate in high fat diet (though not significantly, as the p value was 0.054 and it has to be 0.05 or less to be significant statistically; but it was still a large drop back to a normal rate between 500-600, whereas high fat diet mice had a rate above 600!). You do not want to lower heart rate below the norm - on the other hand, a high fat diet and obesity increase heart rate above the norm and it appears resveratrol restores that, which is a good thing. Also, resveratrol does not lower body temperature, which is also a good thing! Instead, it significantly increases resistance to cold by keeping body temperature even. This means that mitochondria are working efficiently. PMID: 17112576

It is utterly silly to want to lower heart rate and body temperature artificially below the norm, as that will have profound and adverse affects on whole body metabolism, cognitive function, capillary permeability, and blood supply to periferary. Being starved causes lethargy and impaired cognition, which is not a surprise. This stands in contrast of lowering heart rate by strengthening the heart through exercise which keeps blood pressure and flow the same even at the decreased rate, so that tissues will be adequately supplied with oxygen and fuels.

Fourthly, resveratrol at 400mg/kg in mice doubles aerobic capacity and endurance, even over mice on a calorie restricted diet. It also significantly increases strength, motor control, and motor coordination as was stated. PMID: 17112576

Fifthly, only 4.9mg/kg of resveratrol in a mouse changes at least 50% of the same genes as CR and in the same direction. It also mimics the majority of CR metabolic changes without the negative effects of lowered HR and body temp. Resveratrol also prevents age related cardiac dysfunction, and more so than CR (though not statistically significant). PMID: 18523577

Finally, and most condemning, is I have that Cell Metabolism paper here, right in front of me, right now (PMID: 18599363) as anyone can, as its free. And you know what I see? Resveratrol significantly increased life span in high fat diet and every other day feeding mice! Where in the world does the data say they lived shorter, by taking resveratrol? It doesn't! Yes, the increase in lifespan for EOD was with 100mg/kg of resveratrol (what they called light resveratrol, while standard was 400mg/kg), but resveratrol never decreased life span in their data, ever. So, saying it did and in a dose dependant way, is not a simple misrepresentation, it's an outright lie.
Furthermore, resveratrol significantly increased bone density and strength, artery health, and motor coordination beyond what any of the feeding regiments did. It also greatly mimicked EOD feeding at a genetic level (63-96% same genetic changes depending on tissue), and greatly reduced cellular apoptosis same as with EOD.

So, I'm sorry if I sound frank and derisive, as I don't mean to, but I call BS on whatever "press release" you got your post from.

Edit: It should also be noted that the authors of that last paper reported that mice fed 2400mg/kg of resveratrol along with any of the three diets did not have a significant change in life span one way or the other, either. Life span did not decrease, even at such an obscene dose!

Edited by geddarkstorm, 12 December 2008 - 12:25 AM.

[suspire]

Firstly, the average mouse heart rate is between 500-600 bpm, never down in the 300s. So immediately this totally throws a wrench in such data.

Secondly, that paper about heart rate and body temperature that just came out used ob/ob mice, which are genetically messed up to be leptin deficient. Leptin is a hormone that is highly important for metabolism regulation; it also regulates immune response, plays a role in vascular growth, and mice without it are infertile. The response of ob/ob mice to resveratrol, especially their loss of endurance, is impossible to compare to wildtype mice and humans - ob/ob mice are really screwed up mice. Additionally, I can't find where they say what amount of resveratrol they used, though regrettably I can only see their abstract. Saying "human equivalent dose" means nothing, as we have no idea how it was calculated. PMID: 19056839

Thirdly, 400mg/kg resveratrol in mice has been show to lower resting heart rate in high fat diet (though not significantly, as the p value was 0.054 and it has to be 0.05 or less to be significant statistically; but it was still a large drop back to a normal rate between 500-600, whereas high fat diet mice had a rate above 600!). You do not want to lower heart rate below the norm - on the other hand, a high fat diet and obesity increase heart rate above the norm and it appears resveratrol restores that, which is a good thing. Also, resveratrol does not lower body temperature, which is also a good thing! Instead, it significantly increases resistance to cold by keeping body temperature even. This means that mitochondria are working efficiently. PMID: 17112576

It is utterly silly to want to lower heart rate and body temperature artificially below the norm, as that will have profound and adverse affects on whole body metabolism, cognitive function, capillary permeability, and blood supply to periferary. Being starved causes lethargy and impaired cognition, which is not a surprise. This stands in contrast of lowering heart rate by strengthening the heart through exercise which keeps blood pressure and flow the same even at the decreased rate, so that tissues will be adequately supplied with oxygen and fuels.

Fourthly, resveratrol at 400mg/kg in mice doubles aerobic capacity and endurance, even over mice on a calorie restricted diet. It also significantly increases strength, motor control, and motor coordination as was stated. PMID: 17112576

Fifthly, only 4.9mg/kg of resveratrol in a mouse changes at least 50% of the same genes as CR and in the same direction. It also mimics the majority of CR metabolic changes without the negative effects of lowered HR and body temp. Resveratrol also prevents age related cardiac dysfunction, and more so than CR (though not statistically significant). PMID: 18523577

Finally, and most condemning, is I have that Cell Metabolism paper here, right in front of me, right now (PMID: 18599363) as anyone can, as its free. And you know what I see? Resveratrol significantly increased life span in high fat diet and every other day feeding mice! Where in the world does the data say they lived shorter, by taking resveratrol? It doesn't! Yes, the increase in lifespan for EOD was with 100mg/kg of resveratrol (what they called light resveratrol, while standard was 400mg/kg), but resveratrol never decreased life span in their data, ever. So, saying it did and in a dose dependant way, is not a simple misrepresentation, it's an outright lie.
Furthermore, resveratrol significantly increased bone density and strength, artery health, and motor coordination beyond what any of the feeding regiments did. It also greatly mimicked EOD feeding at a genetic level (63-96% same genetic changes depending on tissue), and greatly reduced cellular apoptosis same as with EOD.

So, I'm sorry if I sound frank and derisive, as I don't mean to, but I call BS on whatever "press release" you got your post from.

Thanks, geddarkstorm. That was a very informative response.

[niner]

resveratrol (rez-vair-ah-trawl)

I don't know if they still do this, but certain Taco Bell restaurants in regions apparently not deemed to be hip to the incredibly obscure language known as "Spanish" add helpful pronunciation guides to the menu. This one made me laugh:

Taco (tah-co)

It's how you know that you're getting the real deal, when they know how to pronounce it right...

[Crepulance]

I have a habit of posting "dubious" stuff? Wanna clarify on that, or do you just say babble and hope people won't call you out on it. I'd really like to hear an example of my "dubious" postings, otherwise my dear, you are the dubious one. It was a email from Longevin***. At what point did I deny that? All I did was post it and ask for people to comment on it and evaluate in order to get both sides of the story.

Crep

Crepulance

Save us all the wasted time by stating at the beginning that this is a twisted Longivinex infomercial.

This company is selective and mis representative at best so why would anyone want to waste time chasing up their articles.

I agree that the article reads like a Longevinex press release, but could you explain your own statements in further detail? Why are they mis-representative? Is the information in the article incorrect? I am sure it'd be helpful for the larger audience who isn't quite as focused on these debates/discussions. I'll admit, I also read that article (while searching for info on IP6) and wondered what exactly it implied/meant versus other forms of resveratrol on the market.

Small example of inaccuracy:

250 mg of mineral-chelating (key-lay-ting) molecules, about what is provided in 3-5 glasses of dark red wine

Thats between 50mg and 83mg per glass. But that is not the main point I was making.

The article is one sided ie. it doesn't provide a balanced presentation of the current evidence. They therefore mis represent the current view of the scientific community. Their evidence in not invalid, but it is only part of the picture and therefore mis representative.

New evidence is coming in that water is able to kill, avoid at all costs. Inaccurate? No. Mis representative? ______

You decide.

Fair enough. And Crep has a habit of posting some, uh, dubious stuff. That said, are you saying that basic premise of the pr release is incorrect? That mega-dosing study is incorrect? As for some of the other claims, yeah, I am fairly skeptical. For instance, the whole " significantly affected 9-times more genes"--that seems to me to be because they have Vitamin D, quercetin and IP6 in their formula, not because their resveratrol or their delivery system is somehow superior. If I am wrong about this--and someone else knows more about it than I--please do speak up! But when I read that part, it made me think: Well, sure. If you add X, Y and Z into your formula, it will do other things. But we could just take reservatrol for one supplier, and add quercetin and IP6 to it if we wanted to." But once again, I am unsure where the truth is in all of this stuff.

Still, the focus of the article, the mega-dosing bit, I'd like to hear if people actually think that's incorrect, if the study is somehow flawed or what have you.

[suspire]

I have a habit of posting "dubious" stuff? Wanna clarify on that, or do you just say babble and hope people won't call you out on it. I'd really like to hear an example of my "dubious" postings, otherwise my dear, you are the dubious one. It was a email from Longevin***. At what point did I deny that? All I did was post it and ask for people to comment on it and evaluate in order to get both sides of the story.

Crep

You did not indicate it was an email from L in your initial post. The casual reader might have thought it was an independent news article, rather than a press-release. You could certainly have added a line or two in the beginning about it being from Longevinex, before asking us to evaluate it.

And yeah, the last time you posted a pretty dubious thread? Folstaxan. That one was dubious.

[geddarkstorm]

I have a habit of posting "dubious" stuff? Wanna clarify on that, or do you just say babble and hope people won't call you out on it. I'd really like to hear an example of my "dubious" postings, otherwise my dear, you are the dubious one. It was a email from Longevin***. At what point did I deny that? All I did was post it and ask for people to comment on it and evaluate in order to get both sides of the story.

Crep

I agree with suspire, though, it would have been easier if you'd put that it was a Longevin email either before the text (and put the text in quotes) or in the title. I was at a loss if it was something you had written or if it was a copy of something else (I erred on it being a copy due to its language), till after I posted and saw what Anthony wrote.

Both sides of the story... Their FUD isn't a side of the story - they downright lied. If I hadn't gone to the actual source paper and seen how it was literally the opposite of what they said, it'd be easy to think such crap possible, to stir up controversy.

It's not your fault in any way, shape, or form, Crep. But, don't believe anything they say, anymore. Anyone who outright lies about what's in a research paper to try to push their agenda, on top of misrepresenting and spinning details throughout, and totally fabricates results, are not worth listening to.

[geddarkstorm]

Hey now, no need to fight so personally. A little miscommunication is nothing to attack each other over.

Crep: No worries, Crep. It was only a matter to me about how to respond to the post and you, since it wasn't clear to me at least if the post was your own synthesis of knowledge and opinion, or if it was from some other source trying to be authoritative. Since it was a "press release" trying to be an "authority" to swoon the masses towards their products with fraudulent information, my tone had to be different than for just discussing opinion with someone, and I was worried I'd sound like I was attacking you. Usually, on most forums this isn't an issue, but the level of intellectual discussion on this forum is higher than any I've personally seen, so it wouldnt be a shock to find people around here who could write such concise pieces.

[Crepulance]

Since ImmInst chose to edit and remove our correspondence further on this topic due to its escalation, I do still want to clarify that in no way is it dubious to post about Folstaxan, a supplement with a lot of heat and interest, on a supplement forum.


Crep

I have a habit of posting "dubious" stuff? Wanna clarify on that, or do you just say babble and hope people won't call you out on it. I'd really like to hear an example of my "dubious" postings, otherwise my dear, you are the dubious one. It was a email from Longevin***. At what point did I deny that? All I did was post it and ask for people to comment on it and evaluate in order to get both sides of the story.

Crep

You did not indicate it was an email from L in your initial post. The casual reader might have thought it was an independent news article, rather than a press-release. You could certainly have added a line or two in the beginning about it being from Longevinex, before asking us to evaluate it.

And yeah, the last time you posted a pretty dubious thread? Folstaxan. That one was dubious.

[Brainbox]

 Ass_Cleaner_Small.jpg   10.22KB   9 downloadsOk, you both made your points. Don't become ad-hominem again, that's all there's to it. I don't like cleaning up threads very much to be honest.

Edited by Brainbox, 14 December 2008 - 01:03 PM.

[resveratrol_guy]

Finally, and most condemning, is I have that Cell Metabolism paper here, right in front of me, right now (<a href="http://www.ncbi.nlm....bmed_DefaultRep
ortPanel.Pubmed_RVDocSum" target="_blank">PMID: 18599363</a>) as anyone can, as its free. And you know what I see? Resveratrol significantly increased life span in high fat diet and every other day feeding mice! Where in the world does the data say they lived shorter, by taking resveratrol? It doesn't! Yes, the increase in lifespan for EOD was with 100mg/kg of resveratrol (what they called light resveratrol, while standard was 400mg/kg), but resveratrol never decreased life span in their data, ever. So, saying it did and in a dose dependant way, is not a simple misrepresentation, it's an outright lie.

Now that (I hope) the flame war is over regarding this article, we can evaluate it seriously, without assuming that Longevinex is lying just because it might profit from doing so (even though it would profit more if users had to take more of their pills per day).

geddarkstorm, what you're saying doesn't contradict the article, which is talking about standard-diet (SD) mice, insofar as reduced lifespan is concerned. In Sinclair's study of 2006 or 2007, he demonstrated increased lifespan with high-fat (HF) and CR (or EOD-feeding) mice, but no change with SD mice. This article adds that SD mice suffered a decrease in lifespan with "excessive" reseveratrol dosage. We might debate that result, but they _don't_ say anything above about HF or CR mice. So your comment is correct, but doesn't address their point.

I think the danger is that we may be too fearful of Longevinex's motivations in publishing the article, to the determent of scientific objectivity. Just because they stand to profit does not imply that they're lying. Our lives, in some sense, are dependent on the correct dosage.

Now, I'm not saying that the study is valid or correct, but it deserves more analysis. Even the fact that these mice were genetically messed up doesn't mean that the result is irrelevant; perhaps what's needed is just a better study. But I wouldn't dismiss the article outright.

As an aside, Sinclair's HF mice were moreover high-transfat mice, as he fed them hydrogenated coconut oil. I wonder, then, if the statement that "resveratrol compensates for the damaging effects of a high-fat diet" should really read "...transfat diet". Indeed, if the right fats are used, it seems to me that a high-fat diet is preferable to a standard diet. (This is the premise of the Rosedale diet. Furthermore, early results from a study run by CR researcher Dr. Luigi Fontana seem to show that CR with a higher percentage of calories from fat show results similar to CR, but with the added benefit of lower plasma IGF1; granted, these are preliminary.)

http://www.amazon.co...p...ooks&sr=8-1
http://geriatrics.im...ty/fontana.html

[Anthony_Loera]

Resveratrol Guy,

there are 6 items geddarkstorm addressed in his rather complete post.
Can you go line by line and provide rebuttals for each item?

So far it appears the information that geddarkstorm has provided stands firm in my opinion.

A

[geddarkstorm]

Now that (I hope) the flame war is over regarding this article, we can evaluate it seriously, without assuming that Longevinex is lying just because it might profit from doing so (even though it would profit more if users had to take more of their pills per day).

geddarkstorm, what you're saying doesn't contradict the article, which is talking about standard-diet (SD) mice, insofar as reduced lifespan is concerned. In Sinclair's study of 2006 or 2007, he demonstrated increased lifespan with high-fat (HF) and CR (or EOD-feeding) mice, but no change with SD mice. This article adds that SD mice suffered a decrease in lifespan with "excessive" reseveratrol dosage. We might debate that result, but they _don't_ say anything above about HF or CR mice. So your comment is correct, but doesn't address their point.

I think the danger is that we may be too fearful of Longevinex's motivations in publishing the article, to the determent of scientific objectivity. Just because they stand to profit does not imply that they're lying. Our lives, in some sense, are dependent on the correct dosage.

Now, I'm not saying that the study is valid or correct, but it deserves more analysis. Even the fact that these mice were genetically messed up doesn't mean that the result is irrelevant; perhaps what's needed is just a better study. But I wouldn't dismiss the article outright.

As an aside, Sinclair's HF mice were moreover high-transfat mice, as he fed them hydrogenated coconut oil. I wonder, then, if the statement that "resveratrol compensates for the damaging effects of a high-fat diet" should really read "...transfat diet". Indeed, if the right fats are used, it seems to me that a high-fat diet is preferable to a standard diet. (This is the premise of the Rosedale diet. Furthermore, early results from a study run by CR researcher Dr. Luigi Fontana seem to show that CR with a higher percentage of calories from fat show results similar to CR, but with the added benefit of lower plasma IGF1; granted, these are preliminary.)

http://www.amazon.co...p...ooks&sr=8-1
http://geriatrics.im...ty/fontana.html

Well, you missed the point and what I was saying, Resveratrol_guy, and ironically pulled the very stunt I was lambasting them for: saying I said something I didn't (I only say that to show the point I was trying to make, not berate you or anything). Longevinex PR people lied, flat out, and the very study they cited said the opposite of what they cited it as saying - there's no results to dispute, only them saying the study said something it didn't. They said the one study showed a dose dependent decrease in life span by resveratrol, when that actual study never did! The SD diet mice did not at all, in any way, shape or form, show a significant decrease in life span from resveratrol, even when taking a MASSIVE dose at 2400mg/kg! That's crazy levels, and it didn't hurt them any, apparently. The fact is, and it is a fact, that the "press release" by the longevinex people fabricated information and claimed it as the results of the study. They can't get worst than that, actually making up what was in a study to press their agenda, since the general public isn't going to go read the study for themselves and expose their fraud. I linked the study, you can get it yourself and see exactly what I mean. The actual conclusion was resveratrol never significantly decreases life span, but significantly increases it in EOD and HF diets, even at insane doses - so yes, once again, they lied.

As for the study with the ob/ob mice, which is a completely different study, its results go counter the results of numerous studies in non leptin deficient mice strains, which I also linked. A study that so contradicts several other studies needs extreme scrutiny. As it is, these ob/ob mice are infertile among other horrible phenotypes, and so probably don't even occur in the wild - they are man made. Hence why the results of their study seem rather meaningless other than showing us what we already knew: that leptin is a vital hormonal regulator of whole body metabolism and getting rid of it scrambles the normal metabolic pathways on an organismal level so that they no longer work as they should, thus resveratrol no longer works as it should.

Edited by geddarkstorm, 20 December 2008 - 08:08 AM.

[resveratrol_guy]

Well, you missed the point and what I was saying, Resveratrol_guy, and ironically pulled the very stunt I was lambasting them for: saying I said something I didn't (I only say that to show the point I was trying to make, not berate you or anything). Longevinex PR people lied, flat out, and the very study they cited said the opposite of what they cited it as saying - there's no results to dispute, only them saying the study said something it didn't. They said the one study showed a dose dependent decrease in life span by resveratrol, when that actual study never did! The SD diet mice did not at all, in any way, shape or form, show a significant decrease in life span from resveratrol, even when taking a MASSIVE dose at 2400mg/kg! That's crazy levels, and it didn't hurt them any, apparently. The fact is, and it is a fact, that the "press release" by the longevinex people fabricated information and claimed it as the results of the study. They can't get worst than that, actually making up what was in a study to press their agenda, since the general public isn't going to go read the study for themselves and expose their fraud. I linked the study, you can get it yourself and see exactly what I mean. The actual conclusion was resveratrol never significantly decreases life span, but significantly increases it in EOD and HF diets, even at insane doses - so yes, once again, they lied.

As for the study with the ob/ob mice, which is a completely different study, its results go counter the results of numerous studies in non leptin deficient mice strains, which I also linked. A study that so contradicts several other studies needs extreme scrutiny. As it is, these ob/ob mice are infertile among other horrible phenotypes, and so probably don't even occur in the wild - they are man made. Hence why the results of their study seem rather meaningless other than showing us what we already knew: that leptin is a vital hormonal regulator of whole body metabolism and getting rid of it scrambles the normal metabolic pathways on an organismal level so that they no longer work as they should, thus resveratrol no longer works as it should.

So first of all, I have refined your links to the actual article itself (which as you said, is free, despite confusing peripheral links on the page which say that you can buy it for $31):

Article:

http://www.pubmedcen...bmedid=18599363

Lifespan charts, with these codes:

SD = "standard diet"
HC = "high-calorie"
EOD = "every-other-day diet (intermittant fasting, i.e. approximately CR)"
LR = "low-resveratrol"
R = "(standard) resveratrol"
HR = "high-resveratrol"

http://www.pubmedcen...e...igure&id=F4

As you can see in Chart F, they did 2 SD trials, and one SDHR trial. The SDHR trial, for all statistically significant purposes, produced results right between the 2 SD survival lines. In other words, geddarkstorm, you are correct: high-dose resveratrol in this mouse study did not materially influence standard-diet lifespan one way or the other.

Which means Longevinex' article is wrong:

http://www.longevine.....e Restriction

I plan to call them later today to point out the error.

HOWEVER, their statement is correct, if only you look at HCLR/HCR and EODLR/EODR instead of SDR/SDHR. (Perhaps they just got the categories mixed up, or yes, perhaps they lied.) This is still a significant point, regardless of Longevinex's motivation. If you look at Charts C and D, you can see that low-dose resveratrol mice lived 2-3% longer than standard-dose. That might not sound like much, but how'd you like to live 2 or 3 years longer just by tweaking your dose?

So while taking resveratrol did not decrease life expectancy in any case (with statistical significance), taking more did decrease lifespan, vs. taking less, in the HC and EOD cases.

They also add: "In the lower dose (HCLR) group, maximum lifespan was also increased, while this effect did not reach significance for the higher dose (HCR)". However, since maximum lifespan comes down to a single data point, i.e. the longest lifetime of a large group of mice, it's of questionable statistical significance.

It seems that all mice started resveratrol (if any) at a year of age.

One frustrating thing about the graphs is that they seem to show only about 4% life expectancy improvement for EOD vs. SD, at the 50% survival point, or 8% if combined with low-dose resveratrol. The real benefit seems to be: "if your mouse eats like a pig, then feed him resveratrol and he'll live like an average healthy mouse". If I can't live longer, then at least I want to eat my favorite foods whenever I feel like it (assuming that I at least get sufficient nutrition).

Also... you said that light resveratrol was 100 mg/kg and standard was 400 mg/kg. While technically correct, it's actually in units of mg/kg-of-food, NOT what'd you'd expect in most pharmacology reports, which is mg/kg-of-mouse. So if a human eats, what, 2kg of food per day, then LR in their study would be 200mg. But taking into account metabolic differences, "light" should really be, what, 40-70mg for a human?

And to make matters more confusing, the charts show that SDR is superior to SDLR by the same 2-3%. Maybe this whole LR-vs.-R-vs.-HR thing has low statistical significance. Still, it looks solid in the charts, as the lines rarely change order.

I do wonder whether the addition of omega-3s, quercetin, OPCs, astaxethin, anthocyanin, epicatechin, pterostillbene, daphnephylline, diallyl disulfide, etc. makes any difference. But that's another topic.

Finally, in the study, they claim 26% life extension for HCLR vs. HC. Realize, however, that this is a 26% increase in life expectancy _after_ the first 52 weeks of life. So it's more like 14% of the life expectancy from birth. (This is bound to be a point of confusion with other studies as well.) I don't have any numbers regarding resveratrol's effects when applied immediately upon sexual maturity, which seems to be the optimal time to start dosing and also induce CR.

I'll repost after chatting with Longevinex...

[maxwatt]

(See above post; I've cut it to improve readability)

resveratrol_guy, I appreciate your work it trying to sort through this. This study was the subject of a lot of scrutiny here when it first came out. However some of the differences in the groups of mice you point out may not be statistically significant, meaning they could be due to chance. Another problem if I recall is the strain of mice used are not genetically normal. They have metabolic defects which could obviate the results of any lifespan intervention study. And curiously, the lifespan of even the longest lived mice in the study was shorter than that of the same strain of mouse in other studies. This raises the possibility that something in the lab conditions or food used was killing all the mice prematurely. Net result is that many of us decided to discount the study. It needs to be repeated more carefully.