421 replies to this topic

[phineas]

I just took my first reservatrol this morning. I also added D3 and K2. I take many supplements, Glutamine, potassium, magnesium, calcium, plenty of Omega 3s, Folic Acid, B vitamins and many others. I also regularly (every few weeks) am treated with NeuroMuscular Therapy (NMT) by Paul St John (start of St John method of NMT--now NeuroSomatics).

I'm eager to slim down and tone up. I have pudged out a bit and have become lax in my exercise (used to run, row, bike, dance, lift, nautilus, etc).

As I'm told I'm old now (65 and NOT ELDERLY!!!!) although most of me thinks I'm 17, it's time to get back in shape. I have a personal Pilates trainer for 1/2 hour 3xs a week, to jump start my abs etc. For cardio I have been biking on weekends and, as I get fitter, I will add dancing, treadmill, rowing machine, and nautilus.

As an adult ed teacher, I am on my feet and walking rapidly in my classroom for 5 hours a day -- otherwise I'd be fat instead of pudgy.

Anyway, I am trying to go slowly as I get fit, because if I get tendinitis as I did 12 years ago, I'll probably stop the program and become a fat elderly woman.

It seemed prudent to add resveratrol, D3 and K2 to my supplement regime.

As I cut down on B&Js and add exercise AND resveratrol, I'll keep an eye on this forum and will post any reactions that could be resveratrol related. I am hoping the effects are all good, but I am noting possible ill effects on muscles and tendons. Grrr.

Appreciate any input too.

[Anthony_Loera]

I don't believe the issue is tendonitis.

Tendonitis:

"The most common cause of tendonitis is overuse. Commonly, individuals begin an exercise program, or increase their level of exercise, and begin to experience symptoms of tendonitis. The tendon is unaccustomed to the new level of demand, and this overuse will cause an inflammation and tendonitis.

Another common cause of symptoms of tendonitis is due to age-related changes of the tendon. As people age, the tendons loose their elasticity and ability to glide as smoothly as they used to. With increasing age, individuals are more prone to developing symptoms of tendonitis. The cause of these age-related changes is not entirely understood, but may be due to changes in the blood vessels that supply nutrition to the tendons."

How is it treated?
Usually rest and anti-inflammatory medicine.

Having said that, resveratrol is considered anti-inflammatory, so maybe it is not tendonitis at all.

I understand that you still feel like you are 17, even though you are actually 65. However folks at this age may develop age related issues, maybe you should consult a doctor to verify what it is.
A

Edited by Anthony_Loera, 19 October 2008 - 01:59 AM.

[hmm]

I don't believe the issue is tendonitis.

Tendonitis:

"The most common cause of tendonitis is overuse. Commonly, individuals begin an exercise program, or increase their level of exercise, and begin to experience symptoms of tendonitis. The tendon is unaccustomed to the new level of demand, and this overuse will cause an inflammation and tendonitis.

Another common cause of symptoms of tendonitis is due to age-related changes of the tendon. As people age, the tendons loose their elasticity and ability to glide as smoothly as they used to. With increasing age, individuals are more prone to developing symptoms of tendonitis. The cause of these age-related changes is not entirely understood, but may be due to changes in the blood vessels that supply nutrition to the tendons."

How is it treated?
Usually rest and anti-inflammatory medicine.

Having said that, resveratrol is considered anti-inflammatory, so maybe it is not tendonitis at all.

I understand that you still feel like you are 17, even though you are actually 65. However folks at this age may develop age related issues, maybe you should consult a doctor to verify what it is.
A

I don't understand this post. The original poster said "if I get tendinitis as I did 12 years ago". Why should she go to a doctor to see if what she had 12 years ago was really tendinitis?

[Anthony_Loera]

She also mentions...

"I am hoping the effects are all good, but I am noting possible ill effects on muscles and tendons."

that's what the post was in response to...

A

[Stokestack]

It IS tendonitis. I've seen a doctor and had it verified. And it just gets worse. I quit this garbage months ago and the major sites are just as inflamed as they were when I quit. The latest blow is serious tendonitis above the knee, which I've never experienced in my life. Another fine addition is creeping plantar fasciitis in a hitherto unaffected foot, to go with the raging case that currently hobbles the other foot.

The results of this supposedly vitality-preserving wonder supplement? CRIPPLING TENDONITIS AND A FORCED SEDENTARY LIFESTYLE. I can't even enjoy basic sports with my friends, let alone maintain a rigorous exercise regimen to preserve my health and vitality. And for many people who will try this stuff, it comes at the worst possible stage in life, where recovery may be impossible.

I'm not imagining any of this and I'm not ignoring other possible sources of injury.

IT'S A DISASTER. QUIT THIS STUFF NOW.

[hmm]

She also mentions...

"I am hoping the effects are all good, but I am noting possible ill effects on muscles and tendons."

that's what the post was in response to...

A

Since she only started taking rsv the same day that she was posting, do you think that perhaps she was "noting" the posts mentioning possible ill-effects to be found on this forum? Whatever, I guess we can leave it up to her to clarify...

[hmm]

It IS tendonitis. I've seen a doctor and had it verified. And it just gets worse. I quit this garbage months ago and the major sites are just as inflamed as they were when I quit. The latest blow is serious tendonitis above the knee, which I've never experienced in my life. Another fine addition is creeping plantar fasciitis in a hitherto unaffected foot, to go with the raging case that currently hobbles the other foot.

The results of this supposedly vitality-preserving wonder supplement? CRIPPLING TENDONITIS AND A FORCED SEDENTARY LIFESTYLE. I can't even enjoy basic sports with my friends, let alone maintain a rigorous exercise regimen to preserve my health and vitality. And for many people who will try this stuff, it comes at the worst possible stage in life, where recovery may be impossible.

I'm not imagining any of this and I'm not ignoring other possible sources of injury.

IT'S A DISASTER. QUIT THIS STUFF NOW.

Sorry about the way this is screwing up your life Stokestack. Everybody has their personal take on this. The salesman wants to sell it, the scientists want reliable studies and evidence on it, folks with your kind of unfortunate experience would just as soon burn it. Myself, I am staying with it unless I get a real stern warning otherwise from my body. So far, I find the benefits outweighing the costs, even though I had to suffer through an attack of shingles and a lot of stinky intestinal gas.

I don't discount your experiences at all, but I also don't discount the other folks who have been quite happy with their own experiences. My inclination at this point is that if rsv causes some problems, that the baby shouldn't necessarily be thrown out with the bath water. Maybe the administration of rsv can be tweaked to ensure that it works more favorably for everyone. For instance, maybe it simply needs to be taken along with one or more other substances that might compensate for possible chemical deficiencies rsv might cause...

[pycnogenol]

Does anyone know if Resveratrol spikes (i.e., increases/elevates) liver enzymes in humans? Just curious. Thanks.

Edited by pycnogenol, 22 October 2008 - 03:44 PM.

[davidd]

Does anyone know if Resveratrol spikes (i.e., increases/elevates) liver enzymes in humans? Just curious. Thanks.

This study includes information on resveratrol's effect on phase I and phase II detoxifying enzymes and may provide what you are looking for. Are you looking for something in particular?

...
Toxicogenomics of resveratrol in rat liver

Vidya Hebbar^a, Guoxiang Shen^a, Rong Hu^a, Bok-Ryang Kim^a, Chi Chen^a, Peter J. Korytko^b, James A. Crowell^c, Barry S. Levine^b and A.-N. Tony Kong<sup>a, ,

a</sup>Department of Pharmaceutics, Ernest Mario School of Pharmacy, 160 Frelinghuysen Road, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States ^bToxicology Research Laboratory, University of Illinois at Chicago, Chicago, IL 60612, United States ^cNational Cancer Institute, Rockville, MD, United States
Received 23 April 2004; accepted 7 October 2004. Available online 29 January 2005.


References and further reading may be available for this article. To view references and further reading you must purchase this article.

<H3 class=h3>Abstract</H3>Resveratrol, a polyphenolic compound found in grape skin and peanuts has been shown to prevent many diseases including cardiovascular diseases and cancer. To better understand resveratrol's potential in vivo toxicity, we studied the dose response using cDNA stress arrays coupled with drug metabolizing enzymatic (DME) assays to investigate the expression of stress-responsive genes and Phase I and II detoxifying enzymes in rat livers. Male and female CD rats were treated with high doses of resveratrol (0.3, 1.0 and 3.0 gm/kg/day) for a period of 28 days. Total RNA from rat liver was reverse-transcribed using gene-specific primers and hybridized to stress-related cDNA arrays. Among female rats, Phase I DME genes were repressed at 0.3 and 1.0 gm/kg/day doses, while genes such as manganese superoxide dismutase, cytochrome P450 reductase, quinone oxidoreductase and thiosulfate sulfurtransferase demonstrated a dose-dependent increase in gene expression. The modulation of these liver genes may implicate the potential toxicity as observed among the rats at the highest dose level of resveratrol. Real-Time PCR was conducted on some of the Phase II DME genes and anti-oxidant genes to validate the cDNA array data. The gene expression from real-time PCR demonstrated good correlation with the cDNA array data. UGT1A genes were amongst the most robustly induced especially at the high doses of resveratrol. We next performed Phase I and Phase II enzymatic assays on cytochrome P450 2E1 (CYP2E1), cytochrome P450 1A1 (CYP1A1), NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferase (GST) and UDP-glucuronosyl transferase (UGT). Induction of Phase II detoxifying enzymes was most pronounced at the highest dose of resveratrol. CYP1A1 activity demonstrated a decreasing trend among the 3 dose groups and CYP2E1 activity increased marginally among female rats over controls. In summary, at lower doses of resveratrol there are few significant changes in gene expression whereas the modulation of liver genes at the high dose of resveratrol may implicate the potential toxicity observed.

Keywords: Resveratrol; In vivo; Drug metabolizing enzymes; DNA arrays; Gene expression

Abbreviations: NQO1, NAD(P)H:quinone oxidoreductase; GST, Glutathione S-transferase; UGT, UDP-glucuronosyltransferase; COX, Cyclooxygenase; SOD2, Manganese superoxide dismutase 2
....

I think the low end of dosing is equivalent to something like 6 grams/day in a person (someone on here will correct me if I'm wrong, I'm sure, which is good!). So if that level didn't do much to the liver enzyme production, and if people are affected in the same way as rats, then the amounts that most people are taking would not have much effect on these liver enzymes.

I can tell you that 1500mg of quercetin does seem to increase my UGT1A1 enzyme production. I don't have any enzyme tests to prove this conclusively, but without going into all the details, I'm seeing results consistent with that happening and quercetin is documented to do this. I have a naturally reduced production of enzymes from this gene, due to a genetic mutation. This dose seems to have gotten my enzyme production back to just above the normal range when I was taking it. I took it in 2 divided doses each day.

Is there a particular type of enzyme you are looking to increase?

Thanks,
David

[Dmitri]

It IS tendonitis. I've seen a doctor and had it verified. And it just gets worse. I quit this garbage months ago and the major sites are just as inflamed as they were when I quit. The latest blow is serious tendonitis above the knee, which I've never experienced in my life. Another fine addition is creeping plantar fasciitis in a hitherto unaffected foot, to go with the raging case that currently hobbles the other foot.

The results of this supposedly vitality-preserving wonder supplement? CRIPPLING TENDONITIS AND A FORCED SEDENTARY LIFESTYLE. I can't even enjoy basic sports with my friends, let alone maintain a rigorous exercise regimen to preserve my health and vitality. And for many people who will try this stuff, it comes at the worst possible stage in life, where recovery may be impossible.

I'm not imagining any of this and I'm not ignoring other possible sources of injury.

IT'S A DISASTER. QUIT THIS STUFF NOW.

Sorry about the way this is screwing up your life Stokestack. Everybody has their personal take on this. The salesman wants to sell it, the scientists want reliable studies and evidence on it, folks with your kind of unfortunate experience would just as soon burn it. Myself, I am staying with it unless I get a real stern warning otherwise from my body. So far, I find the benefits outweighing the costs, even though I had to suffer through an attack of shingles and a lot of stinky intestinal gas.

I don't discount your experiences at all, but I also don't discount the other folks who have been quite happy with their own experiences. My inclination at this point is that if rsv causes some problems, that the baby shouldn't necessarily be thrown out with the bath water. Maybe the administration of rsv can be tweaked to ensure that it works more favorably for everyone. For instance, maybe it simply needs to be taken along with one or more other substances that might compensate for possible chemical deficiencies rsv might cause...

I've read that Quercetin and Niacinamide could help since they inhibit some of rsv effects.

[davidd]

It IS tendonitis. I've seen a doctor and had it verified. And it just gets worse. I quit this garbage months ago and the major sites are just as inflamed as they were when I quit. The latest blow is serious tendonitis above the knee, which I've never experienced in my life. Another fine addition is creeping plantar fasciitis in a hitherto unaffected foot, to go with the raging case that currently hobbles the other foot.

The results of this supposedly vitality-preserving wonder supplement? CRIPPLING TENDONITIS AND A FORCED SEDENTARY LIFESTYLE. I can't even enjoy basic sports with my friends, let alone maintain a rigorous exercise regimen to preserve my health and vitality. And for many people who will try this stuff, it comes at the worst possible stage in life, where recovery may be impossible.

I'm not imagining any of this and I'm not ignoring other possible sources of injury.

IT'S A DISASTER. QUIT THIS STUFF NOW.

Sorry about the way this is screwing up your life Stokestack. Everybody has their personal take on this. The salesman wants to sell it, the scientists want reliable studies and evidence on it, folks with your kind of unfortunate experience would just as soon burn it. Myself, I am staying with it unless I get a real stern warning otherwise from my body. So far, I find the benefits outweighing the costs, even though I had to suffer through an attack of shingles and a lot of stinky intestinal gas.

I don't discount your experiences at all, but I also don't discount the other folks who have been quite happy with their own experiences. My inclination at this point is that if rsv causes some problems, that the baby shouldn't necessarily be thrown out with the bath water. Maybe the administration of rsv can be tweaked to ensure that it works more favorably for everyone. For instance, maybe it simply needs to be taken along with one or more other substances that might compensate for possible chemical deficiencies rsv might cause...

I've read that Quercetin and Niacinamide could help since they inhibit some of rsv effects.

I've benefitted from quercetin/bromelain's anti-inflammatory abilities, and that was also while taking resveratrol. Others, like maxwatt, have had the opposite effect. It may be worthwhile to try to see if it helps with the symptoms. It seems to be well tolerated by most, so it could be tried and if it makes the condition worse, it could be stopped, and the worsening should go away.

I don't have any direct experience with niacinamide, but I've read about its anti-inflammatory abilities.

I think you are referring to quercetin and niacinamide's downregulation of the SIRT1 gene (and possibly other sirtuins), compared with resveratrol's upregulation of this gene. It may be possible that SIRT1 activation for some people would cause tendon problems, but my guess is that isn't how it is causing the issues, even if it is causing them. Maybe there is some non-SIRT1 mechanism causing the issues, or maybe, as others have pointed out, it is something mixed with the resveratrol that is causing the issues, rather than the resveratrol chemical itself (emodin, etc.). There are a lot of variables at play here.

One thing a person could do to come closer to an answer would be to take an emodin supplement and see if that produces the same issues, compared with taking a pure resveratrol supplement. I'm not sure what other things might be in the non-pure resveratrol supplements, but I'm sure someone else can provide that information. If those other things were readily available, they could be tried as well. Obviously, this wouldn't be a good idea if the tendon issues are extreme. But if they are just an annoyance, then this type of trial and error might prove useful.

Now that I think about it, I might try this myself (at some future point in time). I've noticed some joint/connective tissue problems. I had some of the pains before taking resveratrol, but some are new. I am taking a 50% pure form of resveratrol. I attribute my pains to iron supplementation in the past, but it would be an interesting thing to test out. I'm not sure how long it would take to prove it though. I've been taking 400 to 600mg of resveratrol for about 5 months and just noticed the new issues a few weeks after I stopped taking the combo of quercetin/bromelain with the resveratrol, so it may have been masking the issue for a while. Or it could all be coincidence.

David

[pycnogenol]

Hi David,

Thanks for the article.

I've recently started taking resveratrol and informed my physician about it so she can chart it in my medical profile.

I also have blood work done on a regular basis since I take prescription medications as well as nutritional supplements.

Does anyone know if Resveratrol spikes (i.e., increases/elevates) liver enzymes in humans? Just curious. Thanks.

This study includes information on resveratrol's effect on phase I and phase II detoxifying enzymes and may provide what you are looking for. Are you looking for something in particular?

Thanks,
David

[Dmitri]

It IS tendonitis. I've seen a doctor and had it verified. And it just gets worse. I quit this garbage months ago and the major sites are just as inflamed as they were when I quit. The latest blow is serious tendonitis above the knee, which I've never experienced in my life. Another fine addition is creeping plantar fasciitis in a hitherto unaffected foot, to go with the raging case that currently hobbles the other foot.

The results of this supposedly vitality-preserving wonder supplement? CRIPPLING TENDONITIS AND A FORCED SEDENTARY LIFESTYLE. I can't even enjoy basic sports with my friends, let alone maintain a rigorous exercise regimen to preserve my health and vitality. And for many people who will try this stuff, it comes at the worst possible stage in life, where recovery may be impossible.

I'm not imagining any of this and I'm not ignoring other possible sources of injury.

IT'S A DISASTER. QUIT THIS STUFF NOW.

Sorry about the way this is screwing up your life Stokestack. Everybody has their personal take on this. The salesman wants to sell it, the scientists want reliable studies and evidence on it, folks with your kind of unfortunate experience would just as soon burn it. Myself, I am staying with it unless I get a real stern warning otherwise from my body. So far, I find the benefits outweighing the costs, even though I had to suffer through an attack of shingles and a lot of stinky intestinal gas.

I don't discount your experiences at all, but I also don't discount the other folks who have been quite happy with their own experiences. My inclination at this point is that if rsv causes some problems, that the baby shouldn't necessarily be thrown out with the bath water. Maybe the administration of rsv can be tweaked to ensure that it works more favorably for everyone. For instance, maybe it simply needs to be taken along with one or more other substances that might compensate for possible chemical deficiencies rsv might cause...

I've read that Quercetin and Niacinamide could help since they inhibit some of rsv effects.

I've benefitted from quercetin/bromelain's anti-inflammatory abilities, and that was also while taking resveratrol. Others, like maxwatt, have had the opposite effect. It may be worthwhile to try to see if it helps with the symptoms. It seems to be well tolerated by most, so it could be tried and if it makes the condition worse, it could be stopped, and the worsening should go away.

I don't have any direct experience with niacinamide, but I've read about its anti-inflammatory abilities.

I think you are referring to quercetin and niacinamide's downregulation of the SIRT1 gene (and possibly other sirtuins), compared with resveratrol's upregulation of this gene. It may be possible that SIRT1 activation for some people would cause tendon problems, but my guess is that isn't how it is causing the issues, even if it is causing them. Maybe there is some non-SIRT1 mechanism causing the issues, or maybe, as others have pointed out, it is something mixed with the resveratrol that is causing the issues, rather than the resveratrol chemical itself (emodin, etc.). There are a lot of variables at play here.

One thing a person could do to come closer to an answer would be to take an emodin supplement and see if that produces the same issues, compared with taking a pure resveratrol supplement. I'm not sure what other things might be in the non-pure resveratrol supplements, but I'm sure someone else can provide that information. If those other things were readily available, they could be tried as well. Obviously, this wouldn't be a good idea if the tendon issues are extreme. But if they are just an annoyance, then this type of trial and error might prove useful.

Now that I think about it, I might try this myself (at some future point in time). I've noticed some joint/connective tissue problems. I had some of the pains before taking resveratrol, but some are new. I am taking a 50% pure form of resveratrol. I attribute my pains to iron supplementation in the past, but it would be an interesting thing to test out. I'm not sure how long it would take to prove it though. I've been taking 400 to 600mg of resveratrol for about 5 months and just noticed the new issues a few weeks after I stopped taking the combo of quercetin/bromelain with the resveratrol, so it may have been masking the issue for a while. Or it could all be coincidence.

David

That could be the case, though if the impurity is causing the problems then why don’t they release a rsv tablet, capsule, etc that has 100% rsv instead of the 50, 98 or 99% I see on the market?

Anyway, reading these type of messages has held me back from using the newer supplements that have no long term studies. At the moment I only use a multi-vitamin/mineral powder, Vitamin D3 liquid soft gels (1,000 IU), Vitamin C (with rose hips) 1,000 mg, drink Green Tea and use 100% cocoa dark chocolate powder which I believe is safer. I’m still contemplating whether or not to use R-Lipoic Acid (there are claims it’s a CR mimic) and quercetin.

[maxwatt]

It IS tendonitis. I've seen a doctor and had it verified. And it just gets worse. I quit this garbage months ago and the major sites are just as inflamed as they were when I quit. The latest blow is serious tendonitis above the knee, which I've never experienced in my life. Another fine addition is creeping plantar fasciitis in a hitherto unaffected foot, to go with the raging case that currently hobbles the other foot.

The results of this supposedly vitality-preserving wonder supplement? CRIPPLING TENDONITIS AND A FORCED SEDENTARY LIFESTYLE. I can't even enjoy basic sports with my friends, let alone maintain a rigorous exercise regimen to preserve my health and vitality. And for many people who will try this stuff, it comes at the worst possible stage in life, where recovery may be impossible.

I'm not imagining any of this and I'm not ignoring other possible sources of injury.

IT'S A DISASTER. QUIT THIS STUFF NOW.

Sorry about the way this is screwing up your life Stokestack. Everybody has their personal take on this. The salesman wants to sell it, the scientists want reliable studies and evidence on it, folks with your kind of unfortunate experience would just as soon burn it. Myself, I am staying with it unless I get a real stern warning otherwise from my body. So far, I find the benefits outweighing the costs, even though I had to suffer through an attack of shingles and a lot of stinky intestinal gas.

I don't discount your experiences at all, but I also don't discount the other folks who have been quite happy with their own experiences. My inclination at this point is that if rsv causes some problems, that the baby shouldn't necessarily be thrown out with the bath water. Maybe the administration of rsv can be tweaked to ensure that it works more favorably for everyone. For instance, maybe it simply needs to be taken along with one or more other substances that might compensate for possible chemical deficiencies rsv might cause...

I've read that Quercetin and Niacinamide could help since they inhibit some of rsv effects.

I've benefitted from quercetin/bromelain's anti-inflammatory abilities, and that was also while taking resveratrol. Others, like maxwatt, have had the opposite effect. It may be worthwhile to try to see if it helps with the symptoms. It seems to be well tolerated by most, so it could be tried and if it makes the condition worse, it could be stopped, and the worsening should go away.

I don't have any direct experience with niacinamide, but I've read about its anti-inflammatory abilities.

I think you are referring to quercetin and niacinamide's downregulation of the SIRT1 gene (and possibly other sirtuins), compared with resveratrol's upregulation of this gene. It may be possible that SIRT1 activation for some people would cause tendon problems, but my guess is that isn't how it is causing the issues, even if it is causing them. Maybe there is some non-SIRT1 mechanism causing the issues, or maybe, as others have pointed out, it is something mixed with the resveratrol that is causing the issues, rather than the resveratrol chemical itself (emodin, etc.). There are a lot of variables at play here.

One thing a person could do to come closer to an answer would be to take an emodin supplement and see if that produces the same issues, compared with taking a pure resveratrol supplement. I'm not sure what other things might be in the non-pure resveratrol supplements, but I'm sure someone else can provide that information. If those other things were readily available, they could be tried as well. Obviously, this wouldn't be a good idea if the tendon issues are extreme. But if they are just an annoyance, then this type of trial and error might prove useful.

Now that I think about it, I might try this myself (at some future point in time). I've noticed some joint/connective tissue problems. I had some of the pains before taking resveratrol, but some are new. I am taking a 50% pure form of resveratrol. I attribute my pains to iron supplementation in the past, but it would be an interesting thing to test out. I'm not sure how long it would take to prove it though. I've been taking 400 to 600mg of resveratrol for about 5 months and just noticed the new issues a few weeks after I stopped taking the combo of quercetin/bromelain with the resveratrol, so it may have been masking the issue for a while. Or it could all be coincidence.

David

That could be the case, though if the impurity is causing the problems then why don’t they release a rsv tablet, capsule, etc that has 100% rsv instead of the 50, 98 or 99% I see on the market?

Anyway, reading these type of messages has held me back from using the newer supplements that have no long term studies. At the moment I only use a multi-vitamin/mineral powder, Vitamin D3 liquid soft gels (1,000 IU), Vitamin C (with rose hips) 1,000 mg, drink Green Tea and use 100% cocoa dark chocolate powder which I believe is safer. I’m still contemplating whether or not to use R-Lipoic Acid (there are claims it’s a CR mimic) and quercetin.

see the "300 MG Trans-Resveratrol Making My Joints Hurt " topic. There is a possibility of heavy metal poisoning from impure product.

[davidd]

It IS tendonitis. I've seen a doctor and had it verified. And it just gets worse. I quit this garbage months ago and the major sites are just as inflamed as they were when I quit. The latest blow is serious tendonitis above the knee, which I've never experienced in my life. Another fine addition is creeping plantar fasciitis in a hitherto unaffected foot, to go with the raging case that currently hobbles the other foot.

The results of this supposedly vitality-preserving wonder supplement? CRIPPLING TENDONITIS AND A FORCED SEDENTARY LIFESTYLE. I can't even enjoy basic sports with my friends, let alone maintain a rigorous exercise regimen to preserve my health and vitality. And for many people who will try this stuff, it comes at the worst possible stage in life, where recovery may be impossible.

I'm not imagining any of this and I'm not ignoring other possible sources of injury.

IT'S A DISASTER. QUIT THIS STUFF NOW.

Sorry about the way this is screwing up your life Stokestack. Everybody has their personal take on this. The salesman wants to sell it, the scientists want reliable studies and evidence on it, folks with your kind of unfortunate experience would just as soon burn it. Myself, I am staying with it unless I get a real stern warning otherwise from my body. So far, I find the benefits outweighing the costs, even though I had to suffer through an attack of shingles and a lot of stinky intestinal gas.

I don't discount your experiences at all, but I also don't discount the other folks who have been quite happy with their own experiences. My inclination at this point is that if rsv causes some problems, that the baby shouldn't necessarily be thrown out with the bath water. Maybe the administration of rsv can be tweaked to ensure that it works more favorably for everyone. For instance, maybe it simply needs to be taken along with one or more other substances that might compensate for possible chemical deficiencies rsv might cause...

I've read that Quercetin and Niacinamide could help since they inhibit some of rsv effects.

I've benefitted from quercetin/bromelain's anti-inflammatory abilities, and that was also while taking resveratrol. Others, like maxwatt, have had the opposite effect. It may be worthwhile to try to see if it helps with the symptoms. It seems to be well tolerated by most, so it could be tried and if it makes the condition worse, it could be stopped, and the worsening should go away.

I don't have any direct experience with niacinamide, but I've read about its anti-inflammatory abilities.

I think you are referring to quercetin and niacinamide's downregulation of the SIRT1 gene (and possibly other sirtuins), compared with resveratrol's upregulation of this gene. It may be possible that SIRT1 activation for some people would cause tendon problems, but my guess is that isn't how it is causing the issues, even if it is causing them. Maybe there is some non-SIRT1 mechanism causing the issues, or maybe, as others have pointed out, it is something mixed with the resveratrol that is causing the issues, rather than the resveratrol chemical itself (emodin, etc.). There are a lot of variables at play here.

One thing a person could do to come closer to an answer would be to take an emodin supplement and see if that produces the same issues, compared with taking a pure resveratrol supplement. I'm not sure what other things might be in the non-pure resveratrol supplements, but I'm sure someone else can provide that information. If those other things were readily available, they could be tried as well. Obviously, this wouldn't be a good idea if the tendon issues are extreme. But if they are just an annoyance, then this type of trial and error might prove useful.

Now that I think about it, I might try this myself (at some future point in time). I've noticed some joint/connective tissue problems. I had some of the pains before taking resveratrol, but some are new. I am taking a 50% pure form of resveratrol. I attribute my pains to iron supplementation in the past, but it would be an interesting thing to test out. I'm not sure how long it would take to prove it though. I've been taking 400 to 600mg of resveratrol for about 5 months and just noticed the new issues a few weeks after I stopped taking the combo of quercetin/bromelain with the resveratrol, so it may have been masking the issue for a while. Or it could all be coincidence.

David

That could be the case, though if the impurity is causing the problems then why don't they release a rsv tablet, capsule, etc that has 100% rsv instead of the 50, 98 or 99% I see on the market?

Anyway, reading these type of messages has held me back from using the newer supplements that have no long term studies. At the moment I only use a multi-vitamin/mineral powder, Vitamin D3 liquid soft gels (1,000 IU), Vitamin C (with rose hips) 1,000 mg, drink Green Tea and use 100% cocoa dark chocolate powder which I believe is safer. I'm still contemplating whether or not to use R-Lipoic Acid (there are claims it's a CR mimic) and quercetin.

see the "300 MG Trans-Resveratrol Making My Joints Hurt " topic. There is a possibility of heavy metal poisoning from impure product.

Hmm, that doesn't sound good. I'll have to check that out.

As for why there isn't an absolutely 100% product, I'm guessing the answer is that it would be cost prohibitive to purify it to that degree?

David

[stephen_b]

I wonder whether serrapeptase might help those having tendonitis issues with resveratrol.

StephenB

[Dmitri]

It IS tendonitis. I've seen a doctor and had it verified. And it just gets worse. I quit this garbage months ago and the major sites are just as inflamed as they were when I quit. The latest blow is serious tendonitis above the knee, which I've never experienced in my life. Another fine addition is creeping plantar fasciitis in a hitherto unaffected foot, to go with the raging case that currently hobbles the other foot.

The results of this supposedly vitality-preserving wonder supplement? CRIPPLING TENDONITIS AND A FORCED SEDENTARY LIFESTYLE. I can't even enjoy basic sports with my friends, let alone maintain a rigorous exercise regimen to preserve my health and vitality. And for many people who will try this stuff, it comes at the worst possible stage in life, where recovery may be impossible.

I'm not imagining any of this and I'm not ignoring other possible sources of injury.

IT'S A DISASTER. QUIT THIS STUFF NOW.

Sorry about the way this is screwing up your life Stokestack. Everybody has their personal take on this. The salesman wants to sell it, the scientists want reliable studies and evidence on it, folks with your kind of unfortunate experience would just as soon burn it. Myself, I am staying with it unless I get a real stern warning otherwise from my body. So far, I find the benefits outweighing the costs, even though I had to suffer through an attack of shingles and a lot of stinky intestinal gas.

I don't discount your experiences at all, but I also don't discount the other folks who have been quite happy with their own experiences. My inclination at this point is that if rsv causes some problems, that the baby shouldn't necessarily be thrown out with the bath water. Maybe the administration of rsv can be tweaked to ensure that it works more favorably for everyone. For instance, maybe it simply needs to be taken along with one or more other substances that might compensate for possible chemical deficiencies rsv might cause...

I've read that Quercetin and Niacinamide could help since they inhibit some of rsv effects.

I've benefitted from quercetin/bromelain's anti-inflammatory abilities, and that was also while taking resveratrol. Others, like maxwatt, have had the opposite effect. It may be worthwhile to try to see if it helps with the symptoms. It seems to be well tolerated by most, so it could be tried and if it makes the condition worse, it could be stopped, and the worsening should go away.

I don't have any direct experience with niacinamide, but I've read about its anti-inflammatory abilities.

I think you are referring to quercetin and niacinamide's downregulation of the SIRT1 gene (and possibly other sirtuins), compared with resveratrol's upregulation of this gene. It may be possible that SIRT1 activation for some people would cause tendon problems, but my guess is that isn't how it is causing the issues, even if it is causing them. Maybe there is some non-SIRT1 mechanism causing the issues, or maybe, as others have pointed out, it is something mixed with the resveratrol that is causing the issues, rather than the resveratrol chemical itself (emodin, etc.). There are a lot of variables at play here.

One thing a person could do to come closer to an answer would be to take an emodin supplement and see if that produces the same issues, compared with taking a pure resveratrol supplement. I'm not sure what other things might be in the non-pure resveratrol supplements, but I'm sure someone else can provide that information. If those other things were readily available, they could be tried as well. Obviously, this wouldn't be a good idea if the tendon issues are extreme. But if they are just an annoyance, then this type of trial and error might prove useful.

Now that I think about it, I might try this myself (at some future point in time). I've noticed some joint/connective tissue problems. I had some of the pains before taking resveratrol, but some are new. I am taking a 50% pure form of resveratrol. I attribute my pains to iron supplementation in the past, but it would be an interesting thing to test out. I'm not sure how long it would take to prove it though. I've been taking 400 to 600mg of resveratrol for about 5 months and just noticed the new issues a few weeks after I stopped taking the combo of quercetin/bromelain with the resveratrol, so it may have been masking the issue for a while. Or it could all be coincidence.

David

That could be the case, though if the impurity is causing the problems then why don't they release a rsv tablet, capsule, etc that has 100% rsv instead of the 50, 98 or 99% I see on the market?

Anyway, reading these type of messages has held me back from using the newer supplements that have no long term studies. At the moment I only use a multi-vitamin/mineral powder, Vitamin D3 liquid soft gels (1,000 IU), Vitamin C (with rose hips) 1,000 mg, drink Green Tea and use 100% cocoa dark chocolate powder which I believe is safer. I'm still contemplating whether or not to use R-Lipoic Acid (there are claims it's a CR mimic) and quercetin.

see the "300 MG Trans-Resveratrol Making My Joints Hurt " topic. There is a possibility of heavy metal poisoning from impure product.

I see, though I’m still weary about putting something in my body that will change gene expression; I think I'll wait for more long term studies.

[unglued]

I don't see a reply to this question from a few months ago:

Were the Sinclair mice in good shape before the tests? Or were they slugs like me?

The mice in Sinclair's experiment published in November 2006 were overfed -- even more than the average American, based on percentage of calories from fat. Or so I've seen mentioned in various sources.

As for exercise, I don't know if they were put just once on a treadmill for the one performance test, or tested regularly. If the latter, they obviously got more exercise than the average person who drives to work, doesn't go to a gym, and doesn't have a giant hand grabbing them periodically and forcing them to run on a treadmill whether they like it or not. One clue is that the media has often called them "couch potato mice". But I don't know what that means: for a mouse, being a couch potato may mean you only spend three hours a day working out on your exercise wheel.

Maybe someone who has access to the original paper and has read it carefully can summarize, better than the journalists, what kind of human the Sinclair mice are the best model of.

[Meta-comment: These various resveratrol topics all seem to naturally wander so much that the lines between them are blurred. Then again, I don't see a topic that would have fit this question exactly anyway.]

[unglued]

Please Post in this Format:
name, RESV in g/day, purity, summary of effects

unglued,1.3,65%,Increased endurance (measured VO2max); Homocysteine may have increased; Return of chronic knee pain; Lower blood pressure; Increased HDL
unglued,0.3,50%,Increased endurance (measured VO2max)

Notes:

• 1.3g and 65% is an estimate. For 6-9 months I was taking 3x 300mg 50% capsules every day and 1/4 teaspoon (but not level teaspoon) of 98% powder (mixed with liqueur and pudding) when convenient.
• For discussion of Vo_{2 max} measurements, see post #1510 ff on "500 Club" topic.
• I also posted certain measurable results in the new Google spreadsheet using this form and so can anyone else.
• Homocysteine not measured until I was on a high dose. Decreased steadily when I lowered dose, took it hours after folic acid, and greatly increased folic acid. Could have made it worse as some suspect, but it's also impossible it could be gradually improving a naturally high level due to a genetic flaw.
• HDL briefly peaked at lifetime record, but correlation isn't obvious, and total cholesterol was higher at same time.

[Anthony_Loera]

Unglued,

this is a great idea, and a good spreadsheet.

thank you for it.

A

Please Post in this Format:
name, RESV in g/day, purity, summary of effects

unglued,1.3,65%,Increased endurance (measured VO2max); Homocysteine may have increased; Return of chronic knee pain; Lower blood pressure; Increased HDL
unglued,0.3,50%,Increased endurance (measured VO2max)

Notes:

• 1.3g and 65% is an estimate. For 6-9 months I was taking 3x 300mg 50% capsules every day and 1/4 teaspoon (but not level teaspoon) of 98% powder (mixed with liqueur and pudding) when convenient.
• For discussion of Vo_{2 max} measurements, see post #1510 ff on "500 Club" topic.
• I also posted certain measurable results in the new Google spreadsheet using this form and so can anyone else.
• Homocysteine not measured until I was on a high dose. Decreased steadily when I lowered dose, took it hours after folic acid, and greatly increased folic acid. Could have made it worse as some suspect, but it's also impossible it could be gradually improving a naturally high level due to a genetic flaw.
• HDL briefly peaked at lifetime record, but correlation isn't obvious, and total cholesterol was higher at same time.

[geddarkstorm]

I don't see a reply to this question from a few months ago:

Were the Sinclair mice in good shape before the tests? Or were they slugs like me?

The mice in Sinclair's experiment published in November 2006 were overfed -- even more than the average American, based on percentage of calories from fat. Or so I've seen mentioned in various sources.

As for exercise, I don't know if they were put just once on a treadmill for the one performance test, or tested regularly. If the latter, they obviously got more exercise than the average person who drives to work, doesn't go to a gym, and doesn't have a giant hand grabbing them periodically and forcing them to run on a treadmill whether they like it or not. One clue is that the media has often called them "couch potato mice". But I don't know what that means: for a mouse, being a couch potato may mean you only spend three hours a day working out on your exercise wheel.

Maybe someone who has access to the original paper and has read it carefully can summarize, better than the journalists, what kind of human the Sinclair mice are the best model of.

[Meta-comment: These various resveratrol topics all seem to naturally wander so much that the lines between them are blurred. Then again, I don't see a topic that would have fit this question exactly anyway.]

There are two answers to that question:

1. They tested each mouse once to get their statistics (8 mice per group), using electric shocks to force them to run till exhaustion. They then tested to see if pain tolerance was different between the groups, and it was not. That is, groups on resveratrol felt no more or less pain than groups not on it, meaning the pain from the shock could not account for the doubled endurance (drop off kinetics were also the same, further supporting this).

2. It doesn't matter. The mice fed resveratrol had paired control groups that underwent exactly the same conditions sans resveratrol. That's how science works, so that only one variable (or a distinguishable set) is being modulated at a time to see it's contribution to an observation. Since all the mice were treated the same, the fact only the resveratrol mice could run twice the distance in both the groups fed high fat diets <i>and the groups fed a standard, healthy diet</i> means the effects were due solely to the resveratrol. This was born out through histological studies, showing a statistical increase in mitochondrial count and surface area in resveratrol fed mice only, as well as other mitochondrial biogenesis and metabolic enhancing gene upregulation that only was in the resveratrol groups.

So yes, it was indeed the resveratrol. That's the wonder of controls.

As for the reports about joints, resveratrol is anti-inflammatory, but the bursa in joints could swell based on changes in fluid regulation. This has nothing to do with inflammation directly, but ion gates, and resveratrol is known to effect calcium ion gates to some extent, which may or may not be physiologically relevant. Tendinitis could be simply due to the swelling of the bursa. How resveratrol could be effecting all this, I don't know, since it's a protective of joints and cartilage directly, the only thing I can think of is the bursa. Truthfully, resveratrol has greatly helped my young joints, and there are others who've benefited much from it in the joint department, so it's hard to say why it improves some yet apparently worsens others, unless the resveratrol is allowing some other, underlying problem to become manifest (perhaps due to its ability to upregulate AMPK in neurons, stimulating their growth and function - which I hypothesize might cause pain if areas neurons were killed off in from repetitive stress began to regenerate). Mice apparently have no problem.

As for cholesterol, it is a very important molecule and increasing it in the blood isn't alone what causes pathologies, it's the type of material it's associated with: namely LDL particles or HDL. LDL has a very low density of cholesterol, whereas HDL is high in cholesterol and acts as a scavenger. Increased levels of HDL will increase blood cholesterol, but this is a good thing. LDL is what can oxidize, causing damage to tissues, form plaques that clog arteries, contribute to diabetes, and so forth. HDL on the other hand, is important for keeping the body healthy and metabolism stimulated, as well as protects against cardiovasculatory disease[ref]. So, increasing cholesterol can actually be a good thing, depending on how it's being increased; the increases you saw were good ones.

In that light, all the values in your spreadsheet show a great boon to health from taking resveratrol that is correlated with dose.

[Spec Tec]

I have been thinking about adding fish oil to my diet. Several years ago I tried it and noticed no results - positive or negative. But I am thinking about trying it again. Any suggestions on brand and dose?

3x caps, 2x daily of Eskimo-brand Omega 3-fish oil.

I've tried a bunch of different store brands and different sources, including the Krill oil stuff. The Eskimo brand (for me) worked the best.

Check the date on the bottle, and keep it in the fridge. Buy smaller bottles instead of larger ones, so that it (hopefully) stays fresher. Take it right before bed, and with lunch.

Biggest difference you'll notice is if you snore. The Omega-3's fix that problem pretty sharpish (note; anecdotal evidence from 6 different people I've asked to try it).

[Spec Tec]

In rats, a slight decrease in copper serum levels: Pretreatment effect of resveratrol on streptozotocin-induced diabetes in rats.

Curiously, aspirin and other NSAIDs also mbilize copper, by chelation, and reduce levels, but no one has suggested they cause tendinitis.

I've gotten and recovered from tendinitis while using resveratrol. IMO, there is no causal connection.

I never got tendinitis until I started taking RSV in very low dosages (16 - 32 m g per day). I was also 50, however, and frequently running very hard up steep hills, which could just as easily have been the cause. Now the best relief from the tendinitis is RSV in higher dosage levels (currently 1.6 grams per day). It would be interesting if lower dosages of RSV caused problems that higher dosages did not.
To me tendinitis itself is not a big deal except as a warning that the affected tendon might rupture. I've seen a few tendinitis reports related to RSV on here, but I haven't seen anyone complain of a rupture. Maybe the RSV (even in small doses) causes some sensitivity without actually damaging any tissue?

Are you sure it's actually tendonitis? Anything that causes inflammation in your armpit and as a result compresses the shallow nerves there could cause very similar symptoms, but most doctors will write them off as tendonitis or carpal tunnel syndrome if you don't mention that as a symptom.

One test is to put a tennis ball in your armpit, and squeeze your arm down to your side. If the pain abates, it's probably something to do with your armpit (possibly inflamed lymph nodes) or the nerves, not the tendons.

[Edit: just read your other posts... sorry for jumping the gun. Keeping the rest up here in case others find it useful though]

Edited by Spec Tec, 10 January 2009 - 12:24 AM.

[hmm]

Are you sure it's actually tendonitis? Anything that causes inflammation in your armpit and as a result compresses the shallow nerves there could cause very similar symptoms, but most doctors will write them off as tendonitis or carpal tunnel syndrome if you don't mention that as a symptom.

One test is to put a tennis ball in your armpit, and squeeze your arm down to your side. If the pain abates, it's probably something to do with your armpit (possibly inflamed lymph nodes) or the nerves, not the tendons.

[Edit: just read your other posts... sorry for jumping the gun. Keeping the rest up here in case others find it useful though]

I know just enough to not make any definitive statements about such complex systems, so who knows? But I will say that all the heel pain I've ever had has always been very directly proportional to the type and degree of strain that I was placing on my legs immediately beforehand.

[davidd]

2. It doesn't matter. The mice fed resveratrol had paired control groups that underwent exactly the same conditions sans resveratrol. That's how science works, so that only one variable (or a distinguishable set) is being modulated at a time to see it's contribution to an observation. Since all the mice were treated the same, the fact only the resveratrol mice could run twice the distance in both the groups fed high fat diets <i>and the groups fed a standard, healthy diet</i> means the effects were due solely to the resveratrol. This was born out through histological studies, showing a statistical increase in mitochondrial count and surface area in resveratrol fed mice only, as well as other mitochondrial biogenesis and metabolic enhancing gene upregulation that only was in the resveratrol groups.

So yes, it was indeed the resveratrol. That's the wonder of controls.

Ah, but it does matter.

Was it exercise+resveratrol that caused the increased VO2 max? If the mice were allowed to run on the treadmill/exercise wheel often (whether taking the full treadmill test or not), then it would require a third set of mice (who were not allowed access to a treadmill/exercise wheel) to determine this distinction. (actually a 5th and 6th set if there were two sets per calorie intake)

That's the wonder of confounding variables.

Now, I have a hunch that this theoretical 5th and 6th set of mice would also show an increase in endurance, but I'm curious how much of a role exercise plays in the resulting VO2 max.

Thanks for the information you provided though. We now have the information that the full treadmill test was only performed once. Do we know if the mice all had the same level of activity up until the treadmill test?

David

[maxwatt]

2. It doesn't matter. The mice fed resveratrol had paired control groups that underwent exactly the same conditions sans resveratrol. That's how science works, so that only one variable (or a distinguishable set) is being modulated at a time to see it's contribution to an observation. Since all the mice were treated the same, the fact only the resveratrol mice could run twice the distance in both the groups fed high fat diets <i>and the groups fed a standard, healthy diet</i> means the effects were due solely to the resveratrol. This was born out through histological studies, showing a statistical increase in mitochondrial count and surface area in resveratrol fed mice only, as well as other mitochondrial biogenesis and metabolic enhancing gene upregulation that only was in the resveratrol groups.

So yes, it was indeed the resveratrol. That's the wonder of controls.

Ah, but it does matter.

Was it exercise+resveratrol that caused the increased VO2 max? If the mice were allowed to run on the treadmill/exercise wheel often (whether taking the full treadmill test or not), then it would require a third set of mice (who were not allowed access to a treadmill/exercise wheel) to determine this distinction. (actually a 5th and 6th set if there were two sets per calorie intake)

That's the wonder of confounding variables.

Now, I have a hunch that this theoretical 5th and 6th set of mice would also show an increase in endurance, but I'm curious how much of a role exercise plays in the resulting VO2 max.

Thanks for the information you provided though. We now have the information that the full treadmill test was only performed once. Do we know if the mice all had the same level of activity up until the treadmill test?

David

I have the paper:
Lagouge et al., Resveratrol Improves Mitochondrial Function and Protects against Metabolic
Disease by Activating SIRT1 and PGC-1a, Cell (2006), doi:10.1016/j.cell.2006.11.013

Method for the endurance test was by

variable speed belt treadmill and incremental speed protocol (range from 18 cm/s to 40 cm/s on
habituated 2 hr fasted mice).

"Habituated" indicates all mice were trained on the treadmill eliminating amount of "training" as a variable. In fact, RSV fed mice compared to controls exhibited reduced spontaneous activity as indicated by observation and recording of caged activity, which was taken to indicate the treadmill performance was due to resveratrol-induced changes.

RSV-fed mice exhibited lower resting heart-rate, and increased muscle strength amd contractile force. This has not been discussed in these forums, though it may have been mentioned.

Only male mice were tested. One would think female mice would exhibit similar effects, but this has not been tested. The strains tested were four to eight week male C57Bl/6J mice from Charles River (L’Arbresle, France) and 8 week male KKAy mice from Clea (Tokyo, Japan)

Bear in mind the mice were fed approximately 400 mg/kg in their chow. The equivalent human dose taking into account relative body mass and surface area would be, as a first approximation, one fifth of that: 80 mg/kg. That would be 2.8 grams for a 70 kg human. There are however major metabolic differences between mice and men. Humans have a significantly more efficient system of enzymes that metabolize phytochemicals. We do not attain nearly as high a serum level of resveratrol as mice at any relative dose. It may be the human equivalent dose is 20 times the mouse dose. Or we may have a delivery system -- human blood protein dissolves resveratrol and may deliver resveratrol to the cellular membrane -- or it may not. Not enough testing has been done in humans. Also, humans differ in the efficiency of their enzymes. East Asians have less efficient CYP450, and consequently require lower doses of certain drugs than (most) westerners. Just as some people are hyper-sensitive to caffeine, and others can drink coffee at night with no sleep disturbance, some people may may be affected by a lower dose of resveratrol than others.

My own experience using a Computrainer cycling ergonometer two years ago, on a daily dose ranging from 1 to 3 grams, was a 10% increase in maximum power output over a trained base-line, and better performance than I'd had with a similar level of training in the past.

[geddarkstorm]

2. It doesn't matter. The mice fed resveratrol had paired control groups that underwent exactly the same conditions sans resveratrol. That's how science works, so that only one variable (or a distinguishable set) is being modulated at a time to see it's contribution to an observation. Since all the mice were treated the same, the fact only the resveratrol mice could run twice the distance in both the groups fed high fat diets <i>and the groups fed a standard, healthy diet</i> means the effects were due solely to the resveratrol. This was born out through histological studies, showing a statistical increase in mitochondrial count and surface area in resveratrol fed mice only, as well as other mitochondrial biogenesis and metabolic enhancing gene upregulation that only was in the resveratrol groups.

So yes, it was indeed the resveratrol. That's the wonder of controls.

Ah, but it does matter.

Was it exercise+resveratrol that caused the increased VO2 max? If the mice were allowed to run on the treadmill/exercise wheel often (whether taking the full treadmill test or not), then it would require a third set of mice (who were not allowed access to a treadmill/exercise wheel) to determine this distinction. (actually a 5th and 6th set if there were two sets per calorie intake)

That's the wonder of confounding variables.

Now, I have a hunch that this theoretical 5th and 6th set of mice would also show an increase in endurance, but I'm curious how much of a role exercise plays in the resulting VO2 max.

Thanks for the information you provided though. We now have the information that the full treadmill test was only performed once. Do we know if the mice all had the same level of activity up until the treadmill test?

David

David,

Again, they were paired controls. That means the controls went through the exact same regiment. If exercise increased VO2 max, then you would have seen it in the controls, and there wouldn't have been a doubling of endurance seen in the resveratrol given mice relative to controls. That's why it doesn't matter, that's why you have controls, which factor in all those variables and allow only the one you are varying to be tested. Only the inclusion or absence of resveratrol was different between the paired groups of mice. Given this was also reproducible (n=8 in all groups), and happened in all feeding groups, it's a real effect, and meets all the criteria of science.

EDIT: Oh, missed your last question. Actually, the resveratrol mice on a high fat diet had significantly less locomotive activity in their cages on a normal basis than the mice not given resveratrol, though they did not have significantly less "rears" than controls. Also, they did not differ significantly in their activities or routines from the controls (went to the same locations as frequently, stayed in the light the same amount of time, etc).

Edited by geddarkstorm, 13 January 2009 - 05:16 PM.

[davidd]

Was it exercise+resveratrol that caused the increased VO2 max? If the mice were allowed to run on the treadmill/exercise wheel often (whether taking the full treadmill test or not), then it would require a third set of mice (who were not allowed access to a treadmill/exercise wheel) to determine this distinction. (actually a 5th and 6th set if there were two sets per calorie intake)

We now have the information that the full treadmill test was only performed once. Do we know if the mice all had the same level of activity up until the treadmill test?

In fact, RSV fed mice compared to controls exhibited reduced spontaneous activity as indicated by observation and recording of caged activity, which was taken to indicate the treadmill performance was due to resveratrol-induced changes.

That's exactly what I was looking for. Thanks maxwatt.

If the mice fed resveratrol were not as active as the other mice, then the chances of their mitochondrial biogenesis being overly influenced by exercise is less.

Did they give details about the treadmill training? Was this a daily thing? Weekly? Only done in the week before the measured test?


You mentioned that they were 4-8 weeks old. Was that when they were begun on Resveratrol, or when they were tested?

Not enough testing has been done in humans. Also, humans differ in the efficiency of their enzymes. East Asians have less efficient CYP450, and consequently require lower doses of certain drugs than (most) westerners. Just as some people are hyper-sensitive to caffeine, and others can drink coffee at night with no sleep disturbance, some people may may be affected by a lower dose of resveratrol than others.

My hunch is that those people with a second pass issue with UGT1A1 (Gilbert's Syndrome/Crigler-Najjar Syndrome) may also require less resveratrol to get an equivalent, effective dose compared with "normal" people.

My own experience using a Computrainer cycling ergonometer two years ago, on a daily dose ranging from 1 to 3 grams, was a 10% increase in maximum power output over a trained base-line, and better performance than I'd had with a similar level of training in the past.

Do you think you could achieve this level of maximum power output if you trained longer/harder, or do you think the resveratrol is allowing you to achieve a level that you otherwise could not achieve, no matter how you prolonged/increased your training?

Thanks again,
David

[geddarkstorm]

From their supplementary data, here's a more in depth overview of their treadmill procedure.

"Endurance Test
An endurance test was performed on 2h fasted mice, using a variable speed belt treadmill
enclosed in a plexiglass chamber with a stimulus device consisting of a shock grid attached to the
rear of the belt (Panlab, Barcelona, Spain). Animals were acclimatized to the test using a
habituation protocol the day preceding the running test. Mice were run at 27 cm/s for 10 min with
a 5o incline. For the actual test, two incremental exercise protocols were used, one for HF fed
animals and one for chow. For chow animals, the experiment was started at 25 cm/s and a 5o
incline whereas for the HF fed animals, which generally weighed more and performed less easily,
the beginning speed was 18 cm/s with a 0o incline. The progressive increase in speed and incline
is summarized in the supplementary online materials and methods section. The distance run and
the number of shocks obtained over 5 min intervals were recorded and a mouse was considered
exhausted and removed from the experiment when it received approximately 100 shocks in a
period of 5 min. "

So, the mice were only put on the treadmill the day before the test, and then the day of the test. They were not on it prior to this.

Edited by geddarkstorm, 13 January 2009 - 05:29 PM.

[davidd]

David,

Again, they were paired controls. That means the controls went through the exact same regiment. If exercise increased VO2 max, then you would have seen it in the controls, and there wouldn't have been a doubling of endurance seen in the resveratrol given mice relative to controls. That's why it doesn't matter, that's why you have controls, which factor in all those variables and allow only the one you are varying to be tested. Only the inclusion or absence of resveratrol was different between the paired groups of mice. Given this was also reproducible, and happened in all feeding groups, it's a real effect, and meets all the criteria of science.

What you are saying is true *if* they compared the controls to another set of controls that were not trained on the treadmills and did not exercise at all. Exercise is the confounding variable that is not being taken into account. Or more precisely, the combination of exercise and resveratrol, which would be a special type of confounding, where two of the independent variables might be additive or multiplicitive in nature. In this case, we already know that one of the independent variables (exercise) causes mitochondrial biogenesis (dependent variable) all by itself. We don't know what resveratrol does all by itself (from this study anyway). We only know how one set of mice that underwent some level of exercise (still not 100% sure on the amount) compared to another set that exercised *and* consumed resveratrol.

It is theoretically possible that another study could show mice that are confined to absolutely no movement do not show mitochondrial biogenesis, even if they are given resveratrol. I don't think the odds are extremely high that this would happen, but I do still wonder how much exercise adds to the total biogenesis effect of resveratrol.

Why do I care? Because it may give us insights into whether people need to exercise in order to get the full benefits of resveratrol. Of course, we still don't know if mitochondria produced through resveratrol alone (no exercise) convey the same health benefits as those produced through a combination of exercise (which probably has other, non-mitochondrial benefits) and resveratrol.

To take this to another extreme, you could probably show that food is another composite, confounding variable. Feed a mouse food and he lives 300 days. Feed a mouse food and resveratrol and he lives 450 days. Feed a mouse only resveratrol and he lives 15 days. It takes food *and* resveratrol to allow the mouse to live a long time.

EDIT: Oh, missed your last question. Actually, the resveratrol mice on a high fat diet had significantly less locomotive activity in their cages on a normal basis than the mice not given resveratrol, though they did not have significantly less "rears" than controls. Also, they did not differ significantly in their activities or routines from the controls (went to the same locations as frequently, stayed in the light the same amount of time, etc).

Hmm....how could they (resveratrol fed mice) have significantly less locomotive activity, yet they did not differ significantly in their activities/routines? Where were the resveratrol mice partaking in this extra locomotive activity, outside their daily routines? Did they get a periodic vaction?

David

Edited by davidd, 13 January 2009 - 06:01 PM.