8 replies to this topic

[Alexon]

Nice article from longevinex:
“Once mega-doses of resveratrol (more than 500 mg) began to be employed, side effects like anemia, Achilles heel tendonitis, anxiety reactions, numbness in the fingers, began to be reported,” says Bill Sardi, spokesperson for Longevinex® (long-jev-in-ex), a leading brand resveratrol dietary supplement. “This is probably because resveratrol is a copper chelator and excessive chelation will impair the availability of copper which is needed for collagen formation and nerve regeneration,” he says. “Resveratrol is relatively safe, but not absolutely safe at any dosage. There are drawbacks,” he adds.

Some online suppliers of resveratrol pills, who have no medical training, irresponsibly recommend up to 7000 milligrams of resveratrol a day. There is also evidence that supra-high dose resveratrol inhibits the absorption of folic acid (vitamin B9), an essential nutrient needed for DNA repair. [European Journal Nutrition 46: 329-36, 2007] High doses have not been tested in humans for long-term use.

Advertising claims by resveratrol supplement makers that their pills exert greater stimulation of the Sirtuin 1 DNA-repair gene should also be regarded with caution since an animal study shows over-stimulation (greater than 7.5 fold) of this gene induces heart failure in animals. [Circulation Research 2007; 100: 1512-21]
more:

Commercial link removed -Funk

Edited by FunkOdyssey, 04 June 2008 - 07:21 PM.

[Anthony_Loera]

Ok, I will be nice.

1- We are not big rats, and heart issue starts at over 12.5 fold, not 7.5. With our human metabolism, I am not sure we can get to 12 fold...
The study he refers to is one called: "Sirt1 regulates aging and resistance to oxidative stress in the heart."

2- The "Mega-doses" reports are from an internet poll taken in this forum. No scientific study backs up the 'reports', and no accredited 3rd parties agree with the 'reports' mentioned in the quote.

Can you not link to the commercial site?

=================================================
From the study:
Sirt1 Regulates Aging and Resistance to Oxidative Stress in the Heart
http://circres.ahajo...ort/100/10/1512

Silent information regulator (Sir)2, a class III histone deacetylase, mediates lifespan extension in model organisms and prevents apoptosis in mammalian cells. However, beneficial functions of Sir2 remain to be shown in mammals in vivo at the organ level, such as in the heart. We addressed this issue by using transgenic mice with heart-specific overexpression of Sirt1, a mammalian homolog of Sir2. Sirt1 was significantly upregulated (4- to 8-fold) in response to pressure overload and oxidative stress in nontransgenic adult mouse hearts. Low (2.5-fold) to moderate (7.5-fold) overexpression of Sirt1 in transgenic mouse hearts attenuated age-dependent increases in cardiac hypertrophy, apoptosis/fibrosis, cardiac dysfunction, and expression of senescence markers. In contrast, a high level (12.5-fold) of Sirt1 increased apoptosis and hypertrophy and decreased cardiac function, thereby stimulating the development of cardiomyopathy. Moderate overexpression of Sirt1 protected the heart from oxidative stress induced by paraquat, with increased expression of antioxidants, such as catalase, through forkhead box O (FoxO)-dependent mechanisms, whereas high levels of Sirt1 increased oxidative stress in the heart at baseline. Thus, mild to moderate expression of Sirt1 retards aging of the heart, whereas a high dose of Sirt1 induces cardiomyopathy. Furthermore, although high levels of Sirt1 increase oxidative stress, moderate expression of Sirt1 induces resistance to oxidative stress and apoptosis. These results suggest that Sirt1 could retard aging and confer stress resistance to the heart in vivo, but these beneficial effects can be observed only at low to moderate doses (up to 7.5-fold) of Sirt1.

Full PDF is here:
http://circres.ahajo...int/100/10/1512

Stress is induced and SIRT1 checked.
"To examine the function of Sirt1 in the adult heart in vivo and to elucidate the role of Sirt1 upregulation during stress and aging. "
=================================================

There is nothing about resveratrol, or how much resveratrol is needed to go to the maximum SIRT1 2.5, 7.5, or 12.5 overexpression found under stress in rats.

A

Edited by Anthony_Loera, 04 June 2008 - 07:56 PM.

[mikeinnaples]

Bill Sardi is so shady. Even if he drastically undercut everyone else's prices, I wouldn't use his product.

This is your first post so I am guessing you are a cohort of Mr. Shady, or perhaps Mr. Shady himself.

[maxwatt]

Bill Sardi is so shady. Even if he drastically undercut everyone else's prices, I wouldn't use his product.

This is your first post so I am guessing you are a cohort of Mr. Shady, or perhaps Mr. Shady himself.

How can you tell when a salesman is lying?


Answer: His lips are moving.

[Mind]

Linking to commercial sites in the forums is discouraged, however, the Navigators are aware that some valuable discussions are impossible without a link and use discretion.

The discussions that are more heavily moderated are ones that seem devoted to promoting/trashing a particular product. Rational/science-based discussions are allowed more leeway.

[Alexon]

Antony
As you don´t have a medical training you can't judge about similarity between rats and human hearts. In article is very good point -"Resveratrol is not food and low doses of resveratrol is more then enough.

Ok, I will be nice.

1- We are not big rats, and heart issue starts at over 12.5 fold, not 7.5. With our human metabolism, I am not sure we can get to 12 fold...
The study he refers to is one called: "Sirt1 regulates aging and resistance to oxidative stress in the heart."

2- The "Mega-doses" reports are from an internet poll taken in this forum. No scientific study backs up the 'reports', and no accredited 3rd parties agree with the 'reports' mentioned in the quote.

Can you not link to the commercial site?

=================================================
From the study:
Sirt1 Regulates Aging and Resistance to Oxidative Stress in the Heart
http://circres.ahajo...ort/100/10/1512

Silent information regulator (Sir)2, a class III histone deacetylase, mediates lifespan extension in model organisms and prevents apoptosis in mammalian cells. However, beneficial functions of Sir2 remain to be shown in mammals in vivo at the organ level, such as in the heart. We addressed this issue by using transgenic mice with heart-specific overexpression of Sirt1, a mammalian homolog of Sir2. Sirt1 was significantly upregulated (4- to 8-fold) in response to pressure overload and oxidative stress in nontransgenic adult mouse hearts. Low (2.5-fold) to moderate (7.5-fold) overexpression of Sirt1 in transgenic mouse hearts attenuated age-dependent increases in cardiac hypertrophy, apoptosis/fibrosis, cardiac dysfunction, and expression of senescence markers. In contrast, a high level (12.5-fold) of Sirt1 increased apoptosis and hypertrophy and decreased cardiac function, thereby stimulating the development of cardiomyopathy. Moderate overexpression of Sirt1 protected the heart from oxidative stress induced by paraquat, with increased expression of antioxidants, such as catalase, through forkhead box O (FoxO)-dependent mechanisms, whereas high levels of Sirt1 increased oxidative stress in the heart at baseline. Thus, mild to moderate expression of Sirt1 retards aging of the heart, whereas a high dose of Sirt1 induces cardiomyopathy. Furthermore, although high levels of Sirt1 increase oxidative stress, moderate expression of Sirt1 induces resistance to oxidative stress and apoptosis. These results suggest that Sirt1 could retard aging and confer stress resistance to the heart in vivo, but these beneficial effects can be observed only at low to moderate doses (up to 7.5-fold) of Sirt1.

Full PDF is here:
http://circres.ahajo...int/100/10/1512

Stress is induced and SIRT1 checked.
"To examine the function of Sirt1 in the adult heart in vivo and to elucidate the role of Sirt1 upregulation during stress and aging. "
=================================================

There is nothing about resveratrol, or how much resveratrol is needed to go to the maximum SIRT1 2.5, 7.5, or 12.5 overexpression found under stress in rats.

A

[Anthony_Loera]

Antony
As you don´t have a medical training you can't judge about similarity between rats and human hearts. In article is very good point -"Resveratrol is not food and low doses of resveratrol is more then enough.

You are absolutely correct, I do not have medical training whatsoever. The closest I had to that was taking care of patients in a nursing home in Utah.

And I agree with you, that a low dose has been found to be good for the heart. This has been stated before.

But I have questions that this article does not answer:

1- How much resveratrol produces a 12.5 fold overexpression of Sirt1... (if resveratrol does this at all since no resveratrol was used in the study?)
2- Would Sirtris 1000x more powerful drug cause instant heart attacks? Since it was given to a rat that lived, I don't think it does...
3- Why would Dr. Sinclair use a 2.5 gram and 5 gram formulation of resveratrol on humans for diabetes? Probably because he found that low doses do nothing for diabetes...
4- Why would GlaxoSmithKline buy Sirtris, and begin steps to produce/promote SRT501 resveratrol formulation that would use 2.5 grams or 5 grams? these guys are much smarter than you and I, I think they understand this safety issue better than both of us.
5- Why would the top SIRT1 researcher go on national television and state Barbara Walters would need 1000 bottles of wine a day worth of Resveratrol? This comes out to 2-7 grams a day...

6- Why would you micronize resveratrol, unless you want more of it to get into the blood stream even though you bash higher dose use?


Simply questions really, but I make an educated choice every day when I take my 2 grams of resveratrol

Cheers
A

Edited by Anthony_Loera, 05 June 2008 - 02:49 PM.

[maxwatt]

Antony
As you don´t have a medical training you can't judge about similarity between rats and human hearts. In article is very good point -"Resveratrol is not food and low doses of resveratrol is more then enough.

Ok, I will be nice.

1- We are not big rats, and heart issue starts at over 12.5 fold, not 7.5. With our human metabolism, I am not sure we can get to 12 fold...
The study he refers to is one called: "Sirt1 regulates aging and resistance to oxidative stress in the heart."

2- The "Mega-doses" reports are from an internet poll taken in this forum. No scientific study backs up the 'reports', and no accredited 3rd parties agree with the 'reports' mentioned in the quote.

...snip....

Actually the toxicity study in rats did not show heart problems, it showed kidney lesions in rats at large doses, over 14 gram equivalent dose in Human, or 7 grams if yo want a safety factor. And these were reversible on cessation. Lethality occured in one or two rats at a much higher dose, and only in one or two rats. Again it was reversible.

[Anthony_Loera]

Antony
As you don´t have a medical training you can't judge about similarity between rats and human hearts. In article is very good point -"Resveratrol is not food and low doses of resveratrol is more then enough.

Ok, I will be nice.

1- We are not big rats, and heart issue starts at over 12.5 fold, not 7.5. With our human metabolism, I am not sure we can get to 12 fold...
The study he refers to is one called: "Sirt1 regulates aging and resistance to oxidative stress in the heart."

2- The "Mega-doses" reports are from an internet poll taken in this forum. No scientific study backs up the 'reports', and no accredited 3rd parties agree with the 'reports' mentioned in the quote.

...snip....

Actually the toxicity study in rats did not show heart problems, it showed kidney lesions in rats at large doses, over 14 gram equivalent dose in Human, or 7 grams if yo want a safety factor. And these were reversible on cessation. Lethality occured in one or two rats at a much higher dose, and only in one or two rats. Again it was reversible.

You are correct Maxwatt, I was thinking he wanted to talk about the study about the heart being stressed and SIRT1 measurements.
A