I'm a new poster, and just found this site yesterday actually. So, just going to say hello. I'm a molecular/cell biologist working on my Ph.D., so let's see if I can help any with trying to understand how resveratrol is functioning with these pains.
I am inclined to think any effects resveratrol has on tendons are mediated by the immune system, inflammation / repair signaling, and have nothing at all to do with copper. Copper chelation feels like an in-vitro red herring, since there is little/no free resveratrol and little/no free copper floating around in humans. This happens when we pubmed jockeys glom onto some obscure idea and extrapolate to the moon with it. 
That seems likely, for more reasons than one.
Firstly, resveratrol is metabolized into conjugates that have glucuronic acid or sulfate put onto its 3' hydroxyl group (which is located on the aromatic ring that has the two hydroxyls and thus is the site for chelation, see pdf
here), making it impossible to chelate copper (PMID: 12523673). Almost no unconjugated resveratrol is ever secreted from the body, so if resveratrol chelated copper, it would be recovered during metabolism of said resveratrol.
Secondly, let's look at this paper
http://www.sciencedi...7885753766ad5dfHere we see the effects of resveratrol on copper is context dependent - that is, it doesn't interact as a chelator when either glutathione or vitamin C are around (and if you are alive, you've got at least glutathione).
Finally, it doesn't matter even if resveratrol acted as a copper chelator unless its Kd was somewhere around the range of copper using proteins and chaperons. For instance, zinc is the second most abundant metal in the body and crucial for proteins as diverse as heme synthesis, to zinc finger transcription factors. Now, citrate, or citric acid, which is part of the TCA cycle and critical for cellular metabolism, is a nice zinc chelator with a Kd of around
1.6X10-5 (or 16 micromolar). However, this does not affect the bioavailability of zinc in the cell as most zinc binding proteins have an even lower Kd. That is, the proteins that need zinc will always get the zinc first.
So, resveratrol could only harm copper metabolism if it could bind copper at a higher affinity than our normal proteins, and keep the copper bound till it was secreted, and this is apparently not the case. Even if it did have a higher Kd, you'd still need a significant ratio of resveratrol verses copper binding proteins to bind up enough of it to transiently pull it out of the body, and I seriously don't see that happening. And again, part of resveratrol being metabolised is the blockage of those hydroxyls needed for chelation, so copper would be released again. Resveratol also has a very short half life in the human body, so it'd be gone long before even its transient effects with metal chelation could cause problems, but not before it activates gene transcription of sirtuin genes from which its benefits are derived.
So then, my guess as to why resveratrol affects tendons might have to do with fluid, or electrolyte levels, and the joint bursa. Since resveratrol can block calcium efflux and influx channels in platelets, it may also in bursa cells and change the fluid levels. But, if that was the case, you'd have accompanied swelling if fluid increased, or joint grinding if it decreased. So, those who have pain, should also look to see if that's happening and that might give us a clue. Afterall, there's a lot of calcium action going on in the joint regions. Moreover, resveratrol could be considered an electrolyte itself, in that it'll change the osmotic conditions of the blood depending on how easily it is taken up into cells. All of this then may be abrogated by drinking a lot more fluid when taking resveratrol if high doses (over 500mg) are used, to try to keep electrolyte levels steady.
Another posibility, is resveratrol might be interacting with the material that makes up the joint and bursa fluids - glucosamino glycans, condroiton sulfates, and the like. I don't see why it would though, or if it'd even get in there. And one last posibility is it could be leading to calcium crystal formation in the joint area which can lead to psuedogrout. But, if that was so, the conditions would be far worst. So, again, it seems like an electrolyte misbalance from what I've read around this site.
@elphaba
Obviously it isn't copper, since increasing copper isn't doing anything. Plantar fasciitis can be caused by things as simple as changing activity levels (walking too much /or/ being idle can both cause it, go figure!), and bearing high amounts of weight over a long period of time - that is a primary cause, so it might have been simply a matter of time.Then again, it starting after taking up resveratrol is interesting. Definitely try taking more fluids and see what happens. There's also always quercetin which is a potent bioflavanoid against inflamation you can take too (also is an anti-viral, anti-cancer, anti-histamine, anti-oxident, and down regulates the innate immune system yet somehow boosts immune system effeciency), instead of things like glucosamine and MSM. There's also evidence that lots of supplements constantly overtime can be harmful, so it may be wise to let your body "detox" by not taking anything for two consequtive days per week (like over the weekend).
Edited by geddarkstorm, 30 November 2008 - 05:33 AM.
LongeCity
