• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

Resveratrol and Joints


  • Please log in to reply
177 replies to this topic

#61 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 25 February 2009 - 05:57 PM

I believe niner has elucidated a major cause of "joint" pain with this post: Interaction with other drugs and/or supplements, involving CYP 3A4 and 2C9 mechanistic inhibition which can lead to myopathies manifested as tendinitis or joint pain.


Yes, this gives us a clear 5th possibility, and one that immediately addresses tendinitis rather than just joint based pain. We should be able to test this rather easily, but painfully, regrettibly, so I can't ask anyone to do this, by using factors that specifically target the CYPs, such as grapefruit. Those CYPs aren't just doing nothing in the body :).

#62 maxwatt

  • Guest, Moderator LeadNavigator
  • 4,941 posts
  • 1,615
  • Location:New York

Posted 25 February 2009 - 06:20 PM

I believe niner has elucidated a major cause of "joint" pain with this post: Interaction with other drugs and/or supplements, involving CYP 3A4 and 2C9 mechanistic inhibition which can lead to myopathies manifested as tendinitis or joint pain.


Yes, this gives us a clear 5th possibility, and one that immediately addresses tendinitis rather than just joint based pain. We should be able to test this rather easily, but painfully, regrettibly, so I can't ask anyone to do this, by using factors that specifically target the CYPs, such as grapefruit. Those CYPs aren't just doing nothing in the body :).


Individual variability in phenotype and amount of these enzymes will complicate this. I'd expect Japanese and some other east Asians to be particularly sensitive/

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

#63 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 25 February 2009 - 08:59 PM

I believe niner has elucidated a major cause of "joint" pain with this post: Interaction with other drugs and/or supplements, involving CYP 3A4 and 2C9 mechanistic inhibition which can lead to myopathies manifested as tendinitis or joint pain.


Yes, this gives us a clear 5th possibility, and one that immediately addresses tendinitis rather than just joint based pain. We should be able to test this rather easily, but painfully, regrettibly, so I can't ask anyone to do this, by using factors that specifically target the CYPs, such as grapefruit. Those CYPs aren't just doing nothing in the body ;).


Individual variability in phenotype and amount of these enzymes will complicate this. I'd expect Japanese and some other east Asians to be particularly sensitive/


Fortunately that too is something easily tested. Perhaps if we added ethnicity to any questionnaire about resveratrol/quercetin/pomegranate associated pains, we could get an ethnic distribution which would answer this assumption nicely.

There is still a problem we have though - tendons are not muscles (different cell types and everything), and myopathy (myocyte problems) does not equal tendinitis, technically, but tendinopathy would (tenocyte problems). We see this distinction reflected in the literature.

The biggest conceptual challenge that remains (for me) is how would these factors, or inhibition of CYP3A4, affect tendons? The vast majority of tendinopathy is caused through strenuous activities and misloading of force on the tenocytes. The exact mechanisms underlying tendinopathies like tendinitis are still largely unknown, but friction rubbing is one major explanation kicking around, related to the two above, where a loss of a smooth gliding surface happens. This also is part of the explanation for why arthritis typically can lead to tendinitis, as the inflamed joint area rubs on the tendon, leading it to inflame too. How in the world would inhibiting CYPs affect tenocytes at all, since CYPs only are involved in the metabolism of mostly xenobiotics, so it would take the loss of the metabolism of some factor, and then that factor going on to affect tenocytes for this link to be possible - so there is somewhere we need to look, and at least we can test with grapefruit juice which is low in quercetin but directly inhibits CYP3A4 quite potently, so we can tease the two apart and investigate CYPs.

However, we may have a lead. We see that tendinopathy (including tendinitis) can be caused by certain drugs like Ciprofloxacin (a broad spectrum antibiotic), and other fluoroquinolone antibiotics. It does so possibly by inhibiting tenocyte migration and causing oxidative stress damage. Ciprofloxacin is also interesting in that its method of antibiotic action is very similar to quercetin's: both inhibit DNA gyrases (which only bacteria have). Since they have similar antibiotic activities, could quercetin and ciprofloxacin affect tenocytes in similar ways? Quercetin is an antioxidant, but like all antioxidants, including resveratrol, a large dose can become pro-oxidant, and these effects manifest at times as pain in the joints. Still, there's no proof that quercetin affects tenocytes, even with all the numerous studies in humans at 1gram doses, but at least there's a possibility due to its likeness with ciprofloxacin in at least one molecular role. What about pomegranate, though?

How then would resveratrol also do this? It isn't known to affect DNA gyrases or act as an antibiotic like quercetin, so already there is a functional difference which attenuates its chance to do the same effects in tenocytes as ciprofloxacin. Could it be some pro-oxidant activity at high doses? Except, the dosage required would be far beyond what can be attained in vivo, theoretically (100s of micromolar range). Though, bioflavanoids will add to each other, so resveratrol plus quercetin will have a synergistic dosage effect (due to quercetin blocking resveratrol metabolization), and one cannot just add the contributions of either together.

So far my searching for a cause is coming up empty. So little is known as to how tenocytes can be affected adversely and lead to tendinopathy. There is also the possibility that resveratrol induced bone density growth could play a role, as calcification can lead to tendinopathy if it occurs too rapidly (friction rubbing and loss of a smooth gliding surface, again). But this seems unlikely, as it would be the norm not the exception if it were the case (unless the people who experience tendinitis have thin bones to begin with, so the density increase for them is more dramatic).

On a final, very very important note that I would like to reiterate from above: tendinopathy (including tendinitis) is not the same as myopathy (muscle pain) or chondropathy (joint pain). Tenocytes (tendon cells) are not the same as myocytes (muscle cells) or chondrocytes (joint cells). More often than not, factors that effect each cell type are different, factors that lead to each pathy are different, and the treatments for each are different.

This is absolutely crucial for everyone to keep in mind. Depending on what type of pathy we are dealing with, the rules and treatments for are most likely different, though there is always a chance they are the same (i.e. statins can affect myocytes and, to a lesser extent, tenocytes). Also, if we are to scan through the literature wisely and not just flail about blindly, we need to know what we are looking for (and what cell type). Please, everyone, keep this in mind. There can be instances of interrelation, but it is in the sense of indirect symptoms from the true pathy source rather than multiple pathy's, more often than not. So, until we know exactly which pathy we are dealing with, or combination of pathy's as resveratrol or other factors could still cause more than one type in different people, and it could be different for different people, we can't proceed with recommending an "antidote" with any confidence. We can only keep investigating and trying to narrow down which one(s) it is.

Edit: Hmm, because statins can cause tendinitis, and are metabolized by CYP3A4, which resveratrol could potentially inhibit at higher doses, I would like to know, if anyone is willing, if those who experienced the tendon/joint pain on resveratrol were taking a statin of any kind, statin mimic, or otherwise statin like drug/supplement.

Edited by geddarkstorm, 25 February 2009 - 09:57 PM.


#64 automita

  • Guest
  • 25 posts
  • 0
  • Location:san diego, ca. usa

Posted 26 February 2009 - 01:08 PM

i take Resveratrol i work out my joints hurt more than ever. it is Resveratrol but the pain is more annoying than debilitating.

#65 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 26 February 2009 - 04:31 PM

i take Resveratrol i work out my joints hurt more than ever. it is Resveratrol but the pain is more annoying than debilitating.


Do you take any other supplements or medicinal drugs of any kind (like a statin)? Get 15 minutes of sunlight a day?

#66 fatboy

  • Guest
  • 286 posts
  • 0

Posted 26 February 2009 - 06:02 PM

Edit: Hmm, because statins can cause tendinitis, and are metabolized by CYP3A4, which resveratrol could potentially inhibit at higher doses, I would like to know, if anyone is willing, if those who experienced the tendon/joint pain on resveratrol were taking a statin of any kind, statin mimic, or otherwise statin like drug/supplement.


Yup, simvastatin 40 mg. Also metformin 1500mg, lisinopril 5mg, and testosterone 10g transdermal if any of those might also compound the effect.

#67 mikeinnaples

  • Guest
  • 1,869 posts
  • 285
  • Location:Florida

Posted 26 February 2009 - 07:14 PM

Yup, simvastatin 40 mg. Also metformin 1500mg, lisinopril 5mg, and testosterone 10g transdermal if any of those might also compound the effect.


My mother had such pain associated with simvistatin that she had to come off of it immediately.


Simvastatin Side Effects


This drug may infrequently cause muscle damage (which can rarely lead to a very serious, possibly fatal, condition called rhabdomyolysis). Seek immediate medical attention if you develop: muscle pain/tenderness/weakness (especially with fever or unusual tiredness).



Also some drug interactrions ....this one is notable because I take high dose niacin AND simvastatin

Use caution if the following drugs are combined with simvastatin because serious side effects such as muscle injury (myopathy) infrequently could occur: fibrates (e.g., gemfibrozil, fenofibrate), high-dose niacin (1 gram or more per day).



#68 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 27 February 2009 - 01:05 AM

Yup, simvastatin 40 mg. Also metformin 1500mg, lisinopril 5mg, and testosterone 10g transdermal if any of those might also compound the effect.


Thank you muchly for the information, fatboy. We now have a supporting piece of evidence for the CYP3A4 inhibition and statin link with resveratrol. If it is true, it'll further suggest resveratrol's true bioavailability is much higher than serum levels indicate, as suggested in rat tissue studies.

It is interesting to note, for me, that statins causing tendinitis is a rare event. If, and so far I must stress the if, there is a connection with resveratrol, CYPs, and statins, the connection would likely manifest on the practical side of things as an increase in the statistical chance to get statin caused tendinitis (and myopathy even more so) with increasing doses of resveratorl. This also means that quercetin will be far more effective at causing tendinitis, and grapefruit juice/pomegranate juice even more effective. At least this is easily testable, and Maxwatt has done some tests with quercetin that correlates along these lines, though I'm unsure if he's on a statin (and I don't know if the drugs he has listed as being on affect tenocytes and/or are metabolized by CYPs).

Edited by geddarkstorm, 27 February 2009 - 01:07 AM.


#69 maxwatt

  • Guest, Moderator LeadNavigator
  • 4,941 posts
  • 1,615
  • Location:New York

Posted 27 February 2009 - 03:00 AM

Yup, simvastatin 40 mg. Also metformin 1500mg, lisinopril 5mg, and testosterone 10g transdermal if any of those might also compound the effect.


Thank you muchly for the information, fatboy. We now have a supporting piece of evidence for the CYP3A4 inhibition and statin link with resveratrol. If it is true, it'll further suggest resveratrol's true bioavailability is much higher than serum levels indicate, as suggested in rat tissue studies.

It is interesting to note, for me, that statins causing tendinitis is a rare event. If, and so far I must stress the if, there is a connection with resveratrol, CYPs, and statins, the connection would likely manifest on the practical side of things as an increase in the statistical chance to get statin caused tendinitis (and myopathy even more so) with increasing doses of resveratorl. This also means that quercetin will be far more effective at causing tendinitis, and grapefruit juice/pomegranate juice even more effective. At least this is easily testable, and Maxwatt has done some tests with quercetin that correlates along these lines, though I'm unsure if he's on a statin (and I don't know if the drugs he has listed as being on affect tenocytes and/or are metabolized by CYPs).

No statins, but CYP metabolized drug = hydrocodone = vicodin = codeine + acetominophen and that is intermittent.

#70 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 28 February 2009 - 06:11 AM

No statins, but CYP metabolized drug = hydrocodone = vicodin = codeine + acetominophen and that is intermittent.


Really doubtful that would cause pain, haha. Your causes are likely something completely different then.

#71 maxwatt

  • Guest, Moderator LeadNavigator
  • 4,941 posts
  • 1,615
  • Location:New York

Posted 28 February 2009 - 12:49 PM

No statins, but CYP metabolized drug = hydrocodone = vicodin = codeine + acetominophen and that is intermittent.


Really doubtful that would cause pain, haha. Your causes are likely something completely different then.


Stopped the pomegranate, and the pain faded.

#72 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 28 February 2009 - 05:24 PM

No statins, but CYP metabolized drug = hydrocodone = vicodin = codeine + acetominophen and that is intermittent.


Really doubtful that would cause pain, haha. Your causes are likely something completely different then.


Stopped the pomegranate, and the pain faded.


I hate asking you to do this.. but would you be willing to try grapefruit juice? It does have some quercetin, but much lower amounts than from a supplement, while being far more potent at inhibiting CYPs than quercetin. If it causes the same pain, then that would further implicate the CYPs as behind this, and then whatever they are being inhibited from metabolizing - might be something we haven't thought of.

Edited by geddarkstorm, 28 February 2009 - 05:24 PM.


#73 maxwatt

  • Guest, Moderator LeadNavigator
  • 4,941 posts
  • 1,615
  • Location:New York

Posted 01 March 2009 - 01:58 AM

No statins, but CYP metabolized drug = hydrocodone = vicodin = codeine + acetominophen and that is intermittent.


Really doubtful that would cause pain, haha. Your causes are likely something completely different then.


Stopped the pomegranate, and the pain faded.


I hate asking you to do this.. but would you be willing to try grapefruit juice? It does have some quercetin, but much lower amounts than from a supplement, while being far more potent at inhibiting CYPs than quercetin. If it causes the same pain, then that would further implicate the CYPs as behind this, and then whatever they are being inhibited from metabolizing - might be something we haven't thought of.

In the past, I've not had trouble with grapefruit juice and resveratrol.

#74 FedAce

  • Validating, Guest
  • 109 posts
  • -11
  • Location:San diego, CA

Posted 01 March 2009 - 05:10 PM

Ok i am in health care myself and our patients are told to stop the Statins if they have signs of Myopathies. but how is this related to Joint pain caused by Resveratrol. ??? Myopathies are NOT related to joint pain, it has to do with muscle tissue breakdown. also does this Joint pain with Resveratrol go away if you stop the drug ???

#75 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 01 March 2009 - 05:16 PM

Ok i am in health care myself and our patients are told to stop the Statins if they have signs of Myopathies. but how is this related to Joint pain caused by Resveratrol. ??? Myopathies are NOT related to joint pain, it has to do with muscle tissue breakdown. also does this Joint pain with Resveratrol go away if you stop the drug ???


Resveratrol is definitely not associated with myopathy from any anecdotal or research evidence. However, it may be associated with tendinitis, which statins also cause, and thus might be an interaction with them. Right now, I'm trying to figure out if what people are experiencing is joint pain - ala aromatase inhibition - or tendinitis - ala CYP metabolization of statins inhibition. At the moment things are unclear; close to pinpointing what it is, but just missing some curcial last bits of info. Namely, what works to stop pain once people start experiencing it.

Stopping the use of resveratrol consistently makes the pain go away, if it was due to resveratrol.

In the past, I've not had trouble with grapefruit juice and resveratrol.


Hm, then that is counter to the CYP3A4 inhibition theory for you. Of course, that theory would only really work if you were getting tendinitis rather than joint pain. Also strengthens our link to statins, but I definitely need to hear from everyone else who's reported tendon pain to see if they were taking statins too to have any confidence in this hypothesis.

On the oootthhherr hand. Quercetin is also an aromatase (CYP19) inhibitor with an IC50 around 30 micromol. Resveratrol, on the other hand, has an IC50 for aromatase inhibition of 40 micromols.

That is, we see that quercetin is more potent than resveratrol at inhibiting aromatase, and thus would be expected to lower estrogen levels even more. Coupled to quercetin's better bioavailability (absorbed far more readily into the body than resveratrol), having much lower doses of quercetin causing joint pain (chondropathy) than resveratrol is expected.

Edited by geddarkstorm, 01 March 2009 - 05:45 PM.


#76 FedAce

  • Validating, Guest
  • 109 posts
  • -11
  • Location:San diego, CA

Posted 01 March 2009 - 05:20 PM

Ok i am in health care myself and our patients are told to stop the Statins if they have signs of Myopathies. but how is this related to Joint pain caused by Resveratrol. ??? Myopathies are NOT related to joint pain, it has to do with muscle tissue breakdown. also does this Joint pain with Resveratrol go away if you stop the drug ???


Resveratrol is definitely not associated with myopathy from any anecdotal or research evidence. However, it may be associated with tendinitis, which statins also cause, and thus might be an interaction with them. Right now, I'm trying to figure out if what people are experiencing is joint pain - ala aromatase inhibition - or tendinitis - ala CYP metabolization of statins inhibition. At the moment things are unclear; close to pinpointing what it is, but just missing some curcial last bits of info. Namely, what works to stop pain once people start experiencing it.

Stopping the use of resveratrol consistently makes the pain go away, if it was due to resveratrol.



Thanks for the info. then it looks like it is Reversable side effect if it is due to Resveratrol to begin with. I just Can't wait to see the reports from Harvard medical school on what they are finding out with their studies on ADR's with resveratrol. Head of this study from Harvard seem so High on this drug. we will have to wait and see.

#77 maxwatt

  • Guest, Moderator LeadNavigator
  • 4,941 posts
  • 1,615
  • Location:New York

Posted 05 March 2009 - 06:50 PM

Ok i am in health care myself and our patients are told to stop the Statins if they have signs of Myopathies. but how is this related to Joint pain caused by Resveratrol. ??? Myopathies are NOT related to joint pain, it has to do with muscle tissue breakdown. also does this Joint pain with Resveratrol go away if you stop the drug ???


Resveratrol is definitely not associated with myopathy from any anecdotal or research evidence. However, it may be associated with tendinitis, which statins also cause, and thus might be an interaction with them. Right now, I'm trying to figure out if what people are experiencing is joint pain - ala aromatase inhibition - or tendinitis - ala CYP metabolization of statins inhibition. At the moment things are unclear; close to pinpointing what it is, but just missing some curcial last bits of info. Namely, what works to stop pain once people start experiencing it.

Stopping the use of resveratrol consistently makes the pain go away, if it was due to resveratrol.

In the past, I've not had trouble with grapefruit juice and resveratrol.


Hm, then that is counter to the CYP3A4 inhibition theory for you. Of course, that theory would only really work if you were getting tendinitis rather than joint pain. Also strengthens our link to statins, but I definitely need to hear from everyone else who's reported tendon pain to see if they were taking statins too to have any confidence in this hypothesis.

On the oootthhherr hand. Quercetin is also an aromatase (CYP19) inhibitor with an IC50 around 30 micromol. Resveratrol, on the other hand, has an IC50 for aromatase inhibition of 40 micromols.

That is, we see that quercetin is more potent than resveratrol at inhibiting aromatase, and thus would be expected to lower estrogen levels even more. Coupled to quercetin's better bioavailability (absorbed far more readily into the body than resveratrol), having much lower doses of quercetin causing joint pain (chondropathy) than resveratrol is expected.


Complicating things further: pomegranate contains a host of phytochemicals besides quercetin in significant amounts: Ellagitannins, Pelargonidin, Punicalin, Punicalagin, Anthocyanins, Cyanidin, Delphinidin, Ellagic Acid. Some of these may be responsible for the interactionsome of us seem to have noted. Cessation of pomegranate and resveratrol seems to have cleared things up almost completely over the past week. I will be resuming resveratrol shortly.

Statin are not on my list of supplements or drugs.

#78 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 06 March 2009 - 12:34 AM

Complicating things further: pomegranate contains a host of phytochemicals besides quercetin in significant amounts: Ellagitannins, Pelargonidin, Punicalin, Punicalagin, Anthocyanins, Cyanidin, Delphinidin, Ellagic Acid. Some of these may be responsible for the interactionsome of us seem to have noted. Cessation of pomegranate and resveratrol seems to have cleared things up almost completely over the past week. I will be resuming resveratrol shortly.

Statin are not on my list of supplements or drugs.


Putting things together even more, we see that pomegranate juice is effective at inhibiting aromatase by up to 60-80% in vitro.

On the other hand, grapefruit juice apparently does not inhibit aromatase, but inhibits other CYPs that break down estrogen, increasing the risk of breast cancer accordingly.

So, grapefruit juice didn't cause you pain associated with resveratrol, and it doesn't inhibit aromatase. Pomegranate and quercetin did cause you pain, and both inhibit aromatase, pomegranate even more so than quercetin alone apparently. Furthermore, quercetin inhibits aromatase considerably better than resveratrol, both directly by the IC50, and by being better absorbed.

This greatly strengthens the correlation of resveratrol associated joint pain with aromatase inhibition activity, lowered estrogen levels, and an imbalance of estrogen to melatonin resulting in somehow causing chondropathy. This is not a conclusive proof in any way, shape, or form, but now we have all cases covered for you and explained by a single phenomenon.

On the flip side, with tendopathy (tendinitis) and resveratrol, so far we've seen a correlation in a case that exhibited it where statins were also in use. Statins can cause myopathy a lot easier than tendopathy, but it is possible the resveratrol may block the myopathy and protect muscles directly, but allow statin caused tendon pain. This is a far weaker correlation, as we'd need a lot more people to tell us if they really had tendinitis and not chondropathy, and if they were also on statins along with resveratrol at the time.

Well, at least it seems we have an emerging, and coherent explanation for the joint pain at least. A few tests could easily prove or disprove it by looking at estrogen levels in those taking resveratrol and exhibiting the pain, and then after ceasing resveratrol and once the pain is gone. And also by seeing if sunlight can help cure it, as is one of the proposed methods for dealing with aromatase inhibitor associated joint pain in breast cancer treatment. Other proposed methods for attenuating that pain could also be used to test and verify if resveratrol is acting through the same way (apparently vitamin D may not be an antidote, which makes sense as resveratrol upregulates the vitamin D receptor anyways)

#79 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 06 March 2009 - 02:31 AM

A quick addendum to my post: resveratrol has been seen to protect skeletal muscles, quite well. This might allow it to protect myocytes from statin or other factor induced myopathy, hence why myopathy has not been seen with resveratrol combined with statins and such.

#80 Happy Gringo

  • Guest
  • 51 posts
  • 1
  • Location:Costa Rica

Posted 06 March 2009 - 06:04 PM

In that case, wouldn't timing be critical if you are training with weights? Wouldn't resveratrol stop muscles from adapting (growing) due to the protection from damage? Not sure what this would mean as far as when to take resveratrol and when to train.

#81 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 07 March 2009 - 05:51 AM

In that case, wouldn't timing be critical if you are training with weights? Wouldn't resveratrol stop muscles from adapting (growing) due to the protection from damage? Not sure what this would mean as far as when to take resveratrol and when to train.


Who says you can't protect muscles from damage and build them? I guess it depends on what you mean by damage. Actual depredation of the muscles, or stress response? I have gained more muscle mass (relative to me) faster while on resveratrol than any other time. All I do is self resistance exercises.

But, anyways, if that's a concern, resveratrol's half life is now known to be 1-3 hours, so take it at least that long before weight training, I would recommend. Unless you want to be a guinea pig and see what happens when you vary intake time verses when you exercise ;).

Edited by geddarkstorm, 07 March 2009 - 06:21 AM.


#82 nowayout

  • Guest
  • 2,946 posts
  • 437
  • Location:Earth

Posted 07 March 2009 - 01:19 PM

But, anyways, if that's a concern, resveratrol's half life is now known to be 1-3 hours, so take it at least that long before weight training, I would recommend. Unless you want to be a guinea pig and see what happens when you vary intake time verses when you exercise <img src="style_emoticons/default/wink.gif" style="vertical-align:middle" emoid=";)" border="0" alt="wink.gif" />.<br />

<br /><br /><br />

Aren't resveratrol's effects on cell switches supposed to extend beyond plasma elimination? But even if not, waiting out the half life might not achieve what you want, since at that point you still have half the original concentration left. You would have to wait for a sufficient number of half lives to get to the point where the concentration ceases to be therapeutic.

#83 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 07 March 2009 - 05:19 PM

But, anyways, if that's a concern, resveratrol's half life is now known to be 1-3 hours, so take it at least that long before weight training, I would recommend. Unless you want to be a guinea pig and see what happens when you vary intake time verses when you exercise <img src="style_emoticons/default/wink.gif" style="vertical-align:middle" emoid=";)" border="0" alt="wink.gif" />.<br />

<br /><br /><br />

Aren't resveratrol's effects on cell switches supposed to extend beyond plasma elimination? But even if not, waiting out the half life might not achieve what you want, since at that point you still have half the original concentration left. You would have to wait for a sufficient number of half lives to get to the point where the concentration ceases to be therapeutic.


Yes indeed, but that depend upon what its critical concentration for effect is, and what level you are taking of it. In the absence of enough resveratrol to maintain them, whatever switches it turned on can always be flipped back off by a new stimulus ahead of their natural flip-back point (exercise is a new stimulus). You may not even have to wait a whole half life for it to lose effect for this biological role. Or you might have to wait 3 (which is 3 hours if the half life is 1 hour, and I think 3 half lifes is probably sufficient to lose most effects). But for the interest of time within a day, 3-6 hours sounds more practical; but it would depend on when you take resveratrol in a day verses when you have time to exercise. So for some people, they would naturally wait longer (like for after work).

Plasma concentration is still a good measure, it's just the plasma concentration of glucuronidated resveratrol must be added to the concentration of aglycone resveratrol according to some proportion constant due to cells de-conjugating resveratrol upon uptake (so that some percentage of glucuronidated resveratrol is no different to the body than aglycone, this is why the bioavailability studies are so confused).

Now, you both are assuming resveratrol would interfere with muscle growth, to which I utterly, respectfully disagree. The idea you have to damage your muscles to grow them is completely false. That's only one pathway by which it works, as it activates stress response. But remember anabolic steroids (or developmental growth in the first place)? They grow muscles far better than exercise, and without needing damage. The reason is that they activate similar anabolic (growth) pathways that the stress response to damage from exercise does too. Well, what does resveratrol do? Going back to that review paper I last cited we see two interesting comments, first one referring to Lagouge et al.'s (2006) work:

"Resveratrol induced myofiber remodeling similar to that
seen by exercise training, but in the absence of increased physical
activity.
"

And

"Secondly, resveratrol also has anti-catabolic effects in skeletalmuscle via
the inhibition of protein degradation.
"

And

"Resveratrol supplementation induced a fiber type transition
from glycolytic type II fibers towards more oxidative type I fibers which
would contribute to increased muscular endurance.
"

It seems more likely that you would want to take resveratrol along with exercise (a little bit before to allow absorption), so that it can synergize the anabolic response and lead to growth. At the same time, resveratrol protects from actual long term damage -- growth plus happy, not so damaged muscles is definitely the better combination to have, I would think.

Edited by geddarkstorm, 07 March 2009 - 05:35 PM.


#84 nowayout

  • Guest
  • 2,946 posts
  • 437
  • Location:Earth

Posted 07 March 2009 - 06:36 PM

Now, you both are assuming resveratrol would interfere with muscle growth, to which I utterly, respectfully disagree.


I wasn't assuming that, just questioning the half life hypothesis. It seems you may well be right. In fact, there are some bodybuilding supplements containing resveratrol that are supposed to help in muscle growth. The justification they usually give for resveratrol's inclusion is its assumed anti-aromatase activity. By depressing estrogen synthesis from testosterone, the body is supposed to compensate by making more testosterone to bring estrogen back to normal (the main signal for testosterone production is apparently estrogen concentration). The studies you cite indicate that there may be additional pathways leading to muscle growth in this case. In fact, I'm thinking it's kind of a pity I never ever dare to try resveratrol again. ;)

#85 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 07 March 2009 - 07:52 PM

Now, you both are assuming resveratrol would interfere with muscle growth, to which I utterly, respectfully disagree.


I wasn't assuming that, just questioning the half life hypothesis. It seems you may well be right. In fact, there are some bodybuilding supplements containing resveratrol that are supposed to help in muscle growth. The justification they usually give for resveratrol's inclusion is its assumed anti-aromatase activity. By depressing estrogen synthesis from testosterone, the body is supposed to compensate by making more testosterone to bring estrogen back to normal (the main signal for testosterone production is apparently estrogen concentration). The studies you cite indicate that there may be additional pathways leading to muscle growth in this case. In fact, I'm thinking it's kind of a pity I never ever dare to try resveratrol again. ;)


Ahh, I'm sorry I thought you were talking about that, tis what I get for posting first thing in the morning haha. The time frame I gave was completely arbitrary, indeed you are totally right to question it, because one would have to do actual studies to see for sure.

Yes, that is too bad to hear. Not everything is for everyone. I wish I could figure out more to help you, but it's hard to say what in the world occurred to give you trouble in the first place :(

#86 yoyo

  • Guest
  • 582 posts
  • 21

Posted 07 March 2009 - 10:44 PM

going from typeII->typeI wouldn't be good for msucle growth.

#87 geddarkstorm

  • Topic Starter
  • Guest
  • 191 posts
  • 30

Posted 08 March 2009 - 12:35 AM

going from typeII->typeI wouldn't be good for msucle growth.


I'm not convinced about that. For instance, intense intermittent training causes the size of Type I muscles to increase, as well as shifts the proportion of Type IIb muscle fibers towards Type I. Furthermore, anabolic steroids do their bulking action by increasing the size of both Type I and Type IIb muscle fibers, but without changing distribution. Remember too, that the proportion and distribution of the two muscle types in a person is also affected by genetics.

Resveratrol seems to increase all muscle parameters -- endurance, strength, and control. At least at the higher doses in mice.

Edited by geddarkstorm, 08 March 2009 - 12:51 AM.


#88 Happy Gringo

  • Guest
  • 51 posts
  • 1
  • Location:Costa Rica

Posted 11 March 2009 - 01:30 PM

Type 1 would increase endurance, but I am convinced that explosive movements are the best way to build muscle (and also stay quick as I age). So I am thinking it would be necessary to also take CoQ10, which has the opposite effect. I wonder what the combination would ultimately do for muscle over time?:

http://www.ncbi.nlm....pubmed/12069109

And as far as the joint pain, this is just a shot in the dark, but what about adding grape seed extract?

Edited by Happy Gringo, 11 March 2009 - 01:35 PM.


#89 caston

  • Guest
  • 2,132 posts
  • 23
  • Location:Perth Australia

Posted 11 March 2009 - 02:48 PM

The joint pain might not actually be a bad thing. Bacteria like Streptococcus pneumoniae likes to accumlulate in and degrade Glycosaminoglycans like Chondroitin and Hyaluronan.

The joint pain may be from the infected cells being killed by the resveratrol and releasing cytokines and such temporarily increasing the pain and inflammation to the area as the immune system runs in like highschool kids running to watch a fight on the oval.

http://www.jbc.org/c...ll/278/50/50596

Edited by caston, 11 March 2009 - 02:53 PM.


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

#90 FedAce

  • Validating, Guest
  • 109 posts
  • -11
  • Location:San diego, CA

Posted 15 March 2009 - 07:43 PM

Another Joint question. I have been taking Res for about 6-7 weeks now and i have some back problems in my Lower back. I began to have this before Resvaratrol but it seems to be Worse now that i have been taking this drug. Not sure if this is just my back getting worse due to excercise i am doing or the Drug is making it worse ???




1 user(s) are reading this topic

0 members, 1 guests, 0 anonymous users