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Had to discontinue Resveratrol because it inhibits healing


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#1 smithx

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Posted 02 February 2011 - 02:00 PM


I was taking 500mg of resveratrol a day, and injured my spine. It wasn't healing well, so I looked into what could improve or retard healing, and found that a number of studies showed that resveratrol slows healing.

So I discontinued resveratrol for several months, and my spine improved. During this time, other injuries also improved, including a partially torn achilles tendon and a partially torn hamstring (yes, I am a bit of a mess).

When things seemed to be in good shape, I started taking 500mg of resveratrol again, and after about 6 weeks, I felt my old injuries returning. The constant dull pain I'd felt in my achilles tendon returned, as did pain in other areas. I was left with no alternative but to discontinue the resveratrol again. After about 2 months, the pain was gone again.

This is by no means proof, but it is a compelling anecdotal case of resveratrol impairing connective tissue healing. So if you have an injury of this type which is not healing, and you are taking resveratrol, try stopping for a few months.

I'm sad about this because I know resveratrol has many benefits, but I need my tendons and my spine to heal, and that seems to take years.

On another note, if anyone is interested in unopened bottles of RevGenetics 500mg 99% pure resveratrol, let me know :)
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#2 maxwatt

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Posted 02 February 2011 - 07:07 PM

Smithx - how are your 25-hydroxy vitamin D levels?

While resveratrol inhibits angiogenesis in vitro, the serum concentration from oral dosing is nowhere near high enough to manifest this effect. I would suspect another explanation/

We know res. is an anti-aromatase, and that medicines that do this cause can cause joint and tendon pain. The treatment is sunlight and/or vitamin D3 supplements. From reports here, I beleive raising ones vitamin D level to well above 30, and perhaps above 40, eliminates such symptoms.
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#3 2tender

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Posted 05 February 2011 - 03:36 PM

Theres an article at ergo-log.com that suggests the opposite, regarding spine and disks. I agree that vitamin D is helpful. Making a broad sweeping comment that Res. isnt helping you heal doesnt sound fair or accurate. There are many other factors involved. If Resveratrol isnt working for you, and apparently there are some people that cant take it, simply stop using it.. Supplementation is trial and error, What works for you may not work for others. Our personal biology dictates what is useful and what isnt as well as when. If you are taking pain medication and this includes aspirin, it could affect supplement benefits. I think our physiology is extremely complex and that learning what is beneficial for us at any given time is prudent...

#4 Marios Kyriazis

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Posted 05 February 2011 - 07:27 PM

It is well known that megadoses of resveratrol bind copper and this affects collagen healing. Anything over 200-300mg a day will cause this. I don't see the rationale for taking more than 10-15mg of resveratrol a day, as this dose is ideal for its anti-aging (Sir2) benefits. If you take enormous doses of any supplements you are bound to experience side effects. Big isn't always good.
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#5 okok

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Posted 05 February 2011 - 07:40 PM

I wonder if res would contribute to facial collagen and fat loss, as i've noticed this over the last years, though i understand it's common with aging.

#6 maxwatt

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Posted 05 February 2011 - 09:05 PM

It is well known that megadoses of resveratrol bind copper and this affects collagen healing. Anything over 200-300mg a day will cause this. I don't see the rationale for taking more than 10-15mg of resveratrol a day, as this dose is ideal for its anti-aging (Sir2) benefits. If you take enormous doses of any supplements you are bound to experience side effects. Big isn't always good.


This has become an urban legend. The binding of copper by resveratrol is miniscule, and at any physiologically obtainable concentration would have no effect.

#7 Lufega

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Posted 06 February 2011 - 07:54 PM

Here's a thought. Resveratrol upregulates Superoxide dismutase. All of them. That means it's "chelating" or using up zinc, copper and manganese. These three minerals are involved in healing of wounds of all kinds. Could it be that you're not getting enough of these in your diet to maintain the activity of reveratrol ?

#8 niner

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Posted 07 February 2011 - 06:13 AM

Here's a thought. Resveratrol upregulates Superoxide dismutase. All of them. That means it's "chelating" or using up zinc, copper and manganese. These three minerals are involved in healing of wounds of all kinds. Could it be that you're not getting enough of these in your diet to maintain the activity of reveratrol ?

I dunno. Mn SODs have molecular weights in the 20-40kdal range, so to use up one mg of Mn, you would need to synthesize...

0.001g Mn * (mole Mn/55g Mn) * (30000g SOD/m) = 0.55g MnSOD.

Half a gram sounds like a lot of SOD. I don't know how many mg of Mn we might have in our body stores. They saw SOD upregulation in vitro, probably with pretty high concentrations. Would you really get enough in vivo to use up your Mn? (or zinc or copper) I guess I couldn't rule it out, but it seems like a long shot. No harm in making sure you have adequate micronutrients, though.

#9 Marios Kyriazis

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Posted 07 February 2011 - 10:32 AM

It is well known that megadoses of resveratrol bind copper and this affects collagen healing. Anything over 200-300mg a day will cause this. I don't see the rationale for taking more than 10-15mg of resveratrol a day, as this dose is ideal for its anti-aging (Sir2) benefits. If you take enormous doses of any supplements you are bound to experience side effects. Big isn't always good.


This has become an urban legend. The binding of copper by resveratrol is miniscule, and at any physiologically obtainable concentration would have no effect.


I hope the binding of copper by resveratrol DOES have a physiological effect. Binding of copper in this case is beneficial as it reduces mutagenic activity of DNA.

See also:
http://www.springerl...14x454800r2522/

#10 maxwatt

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Posted 07 February 2011 - 12:00 PM

It is well known that megadoses of resveratrol bind copper and this affects collagen healing. Anything over 200-300mg a day will cause this. I don't see the rationale for taking more than 10-15mg of resveratrol a day, as this dose is ideal for its anti-aging (Sir2) benefits. If you take enormous doses of any supplements you are bound to experience side effects. Big isn't always good.


This has become an urban legend. The binding of copper by resveratrol is miniscule, and at any physiologically obtainable concentration would have no effect.


I hope the binding of copper by resveratrol DOES have a physiological effect. Binding of copper in this case is beneficial as it reduces mutagenic activity of DNA.

See also:
http://www.springerl...14x454800r2522/


Thanks for the link, butI do not have access to the entire article. The concentration they used to prevent DNA breakage in lymphocytes in other studies was far higher than can be obtained by oral administration, except perhaps transiently in the gut. If you want a copper chelator to deal with DNA breakage, one such is aspirin, which is orders of magnitude stronger than resveratrol in that regard.

#11 Lufega

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Posted 07 February 2011 - 09:22 PM

Here's a thought. Resveratrol upregulates Superoxide dismutase. All of them. That means it's "chelating" or using up zinc, copper and manganese. These three minerals are involved in healing of wounds of all kinds. Could it be that you're not getting enough of these in your diet to maintain the activity of reveratrol ?

I dunno. Mn SODs have molecular weights in the 20-40kdal range, so to use up one mg of Mn, you would need to synthesize...

0.001g Mn * (mole Mn/55g Mn) * (30000g SOD/m) = 0.55g MnSOD.

Half a gram sounds like a lot of SOD. I don't know how many mg of Mn we might have in our body stores. They saw SOD upregulation in vitro, probably with pretty high concentrations. Would you really get enough in vivo to use up your Mn? (or zinc or copper) I guess I couldn't rule it out, but it seems like a long shot. No harm in making sure you have adequate micronutrients, though.


Consider that getting 100 mg of resveratrol is way higher than anything you get in your diet naturally. Now imagine people here who use it in the grams !

#12 niner

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Posted 08 February 2011 - 12:55 AM

Here's a thought. Resveratrol upregulates Superoxide dismutase. All of them. That means it's "chelating" or using up zinc, copper and manganese. These three minerals are involved in healing of wounds of all kinds. Could it be that you're not getting enough of these in your diet to maintain the activity of reveratrol ?

I dunno. Mn SODs have molecular weights in the 20-40kdal range, so to use up one mg of Mn, you would need to synthesize...

0.001g Mn * (mole Mn/55g Mn) * (30000g SOD/m) = 0.55g MnSOD.

Half a gram sounds like a lot of SOD. I don't know how many mg of Mn we might have in our body stores. They saw SOD upregulation in vitro, probably with pretty high concentrations. Would you really get enough in vivo to use up your Mn? (or zinc or copper) I guess I couldn't rule it out, but it seems like a long shot. No harm in making sure you have adequate micronutrients, though.

Consider that getting 100 mg of resveratrol is way higher than anything you get in your diet naturally. Now imagine people here who use it in the grams !

Whether it's natural or not doesn't matter. What matters is the resveratrol blood level that is achieved from whatever dose you're taking, and the response of the various SOD enzymes. In the paper you referenced on MnSOD, they bathed isolated cells in a solution of resveratrol for several weeks. I couldn't tell what concentration was used from the abstract, other than it being described as micromolar levels, meaning that it's at least one micromolar and is less than millimolar. Unless you are taking multiple grams of resveratrol, it is hard to reach one micromolar even for minutes, much less days on end. Remember that in an intact organism, there is a xenobiotic metabolic system that is constantly sucking up compounds like resveratrol, so they don't stick around for long.

#13 capsun

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Posted 08 February 2011 - 01:36 AM

If it did indeed slow healing, this is probably a good thing (if it's due to the CR-mimetic gene expression). Again, this is why (for instance) mice on resveratrol have greater bone health when they are older. The resveratrol slows bone turnover (and thus osteoporosis). Of course, if you're getting injured all the time, it's a not-so-good thing.

Edited by capsun, 08 February 2011 - 01:36 AM.


#14 niner

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Posted 08 February 2011 - 03:59 AM

If it did indeed slow healing, this is probably a good thing (if it's due to the CR-mimetic gene expression). Again, this is why (for instance) mice on resveratrol have greater bone health when they are older. The resveratrol slows bone turnover (and thus osteoporosis). Of course, if you're getting injured all the time, it's a not-so-good thing.

Resveratrol slows bone turnover? Does it inhibit resorption? Or does it enhance bone formation, or perhaps both? Where did you run across this?

#15 maxwatt

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Posted 08 February 2011 - 12:31 PM

If it did indeed slow healing, this is probably a good thing (if it's due to the CR-mimetic gene expression). Again, this is why (for instance) mice on resveratrol have greater bone health when they are older. The resveratrol slows bone turnover (and thus osteoporosis). Of course, if you're getting injured all the time, it's a not-so-good thing.

Resveratrol slows bone turnover? Does it inhibit resorption? Or does it enhance bone formation, or perhaps both? Where did you run across this?


This is new to me too. Whether it translates into a measurable effect at practical doses is another question.

Exp Cell Res. 2009 Oct 15;315(17):2953-62. Epub 2009 Aug 6.
Resveratrol augments the canonical Wnt signaling pathway in promoting osteoblastic differentiation of multipotent mesenchymal cells.
Zhou H, Shang L, Li X, Zhang X, Gao G, Guo C, Chen B, Liu Q, Gong Y, Shao C.

Institute of Molecular Medicine and Genetics, Shandong University, Shandong 250012, China.
Abstract
Resveratrol has been shown to possess many health-benefiting effects, including the promotion of bone formation. In this report we investigated the mechanism by which resveratrol promotes osteoblastic differentiation from pluripotent mesenchymal cells. Since Wnt signaling is well documented to induce osteoblastogenesis and bone formation, we characterized the factors involved in Wnt signaling in response to resveratrol treatment. Resveratrol treatment of mesenchymal cells led to an increase in stabilization and nuclear accumulation of beta-catenin dose-dependently and time-dependently. As a consequence of the increased nuclear accumulation of beta-catenin, the ability to activate transcription of beta-catenin-TCF/LEF target genes that are required for osteoblastic differentiation was upregulated. However, resveratrol did not affect the initial step of the Wnt signaling pathway, as resveratrol was as effective in upregulating the activity of beta-catenin in cells in which Lrp5 was knocked down as in control cells. In addition, while conditioned medium enriched in Wnt signaling antagonist Dkk1 was able to inhibit Wnt3a-induced beta-catenin upregulation, this inhibitory effect can be abolished in resveratrol-treated cells. Furthermore, we showed that the level of glycogen synthase kinase 3beta (GSK-3beta), which phosphorylates and destabilizes beta-catenin, was reduced in response to resveratrol treatment. The phosphorylation of GSK-3beta requires extracellular signal-regulated kinase (ERK)1/2. Together, our data indicate that resveratrol promotes osteoblastogenesis and bone formation by augmenting Wnt signaling.

PMID: 19665018

Cancer Res. 2005 Nov 1;65(21):9943-52.
Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoblast differentiation.
Boissy P, Andersen TL, Abdallah BM, Kassem M, Plesner T, Delaissé JM.

Clinical Research Unit and Division of Hematology, Vejle Hospital, Vejle, Southern Denmark University Network, Denmark. patboi@vgs.vejleamt.dk
Abstract
Multiple myeloma is characterized by the accumulation of clonal malignant plasma cells in the bone marrow, which stimulates bone destruction by osteoclasts and reduces bone formation by osteoblasts. In turn, the changed bone microenvironment sustains survival of myeloma cells. Therefore, a challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts. Because resveratrol (trans-3,4',5-trihydroxystilbene) is reported to display antitumor activities on a variety of human cancer cells, we investigated the effects of this natural compound on myeloma and bone cells. We found that resveratrol reduces dose-dependently the growth of myeloma cell lines (RPMI 8226 and OPM-2) by a mechanism involving cell apoptosis. In cultures of human primary monocytes, resveratrol inhibits dose-dependently receptor activator of nuclear factor-kappaB (NF-kappaB) ligand-induced formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells, TRACP activity in the medium, up-regulation of cathepsin K gene expression, and bone resorption. These inhibitions are associated with a down-regulation of RANK expression at both mRNA and cell surface protein levels and a decrease of NFATc1 stimulation and NF-kappaB nuclear translocation, whereas the gene expression of c-fms, CD14, and CD11a is up-regulated. Finally, resveratrol promotes dose-dependently the expression of osteoblast markers like osteocalcin and osteopontin in human bone marrow mesenchymal stem cells (hMSC-TERT) and stimulates their response to 1,25(OH)2 vitamin D3 [1,25(OH)2D3]. Moreover, resveratrol up-regulates dose-dependently the expression of 1,25(OH)2D3 nuclear receptor. Taken together, these results suggest that resveratrol or its derivatives deserve attention as potential drugs for treating multiple myeloma.

PMID: 16267019



#16 walbargain

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Posted 08 February 2011 - 04:41 PM

Hello SmithX,

I too am taking the RevGenetics Resveratrol at normal dosage amounts. I recently had knee surgery and noticed my knee was not healing at all and that my ruptured disc in my back and my plantar fascitis was worsening. I had to stop the Res-V for awhile and the knee is improving and so is the back pain and joint pain.

One caveat is that I have Lymes which complicates the issue. I am supplementing with Vitamin D3 because I am deficient in Vitamin D.

If Resveratrol is a chelator of these minerals, Zinc, Copper and Manganese I would also consider supplementing as the benefits of supplementing with proper amounts of Resveratrol seem to be many. I am attempting to overcome Neurological deficits by up-regulating my MitoChondrial Function and do not wish to stop the Res-V. I may step up the D3 supplementation since I am already Vitamin D deficient.

But I just wanted to comment that my joint pain has worsened and I also have experienced slow healing while on ResV. I did not have as much pain while on the Nitro250 as I have on the NitroMX. I will likely try smaller doses of ResV at maybe 250mg of Trans-Resveratrol and up my dosage of D3 and consider the copper, manganese and Zinc supplementation. I already supplement with Zinc as it seems to be a natural aphrodisiac similar to eating Oysters like we do here in Florida! LOL

Would certainly appreciate more information from anyone who has also experienced these effects from Resveratrol supplementation. In particular if Vitamin D in greater amounts alleviated the joint pain or of Zinc and copper and Manganese alleviated the joint pain and/or slow healing.

Thanks!

#17 maxwatt

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Posted 08 February 2011 - 05:26 PM

. . . .
Would certainly appreciate more information from anyone who has also experienced these effects from Resveratrol supplementation. In particular if Vitamin D in greater amounts alleviated the joint pain or of Zinc and copper and Manganese alleviated the joint pain and/or slow healing.

Thanks!


Have you tested your levels of 25-hydroxy D3? Until I raised my levels to 36 ng/ml I had problems with tendon pain, though resveratrol at >=600mg/day was reducing my arthritis symptoms. I need to take 5000 units to maintain this level. I know of another resveratrol user who still experienced such pain at 43 ng/ml, so you might want to aim for a level around 50.

I had no issues with mineral chelation, and doubt resveratrol's ability to deplete mineral levels at the serum levels one can get from a supplement. If you were injecting it, that might be another matter, but we are not. Oral resveratrol results in serum levels measured in 10's or at most a few hundred nano-grams/ml. The in vitro concentration needed to show chelation in cultured cells is a thousand times greater or more. Chelation is not really an issue.

What we believe is happening, is that resveratrol does show sufficient anti-aromatase activity to result in symptoms of joint or tendon pain, similar to that in anti-aromatase medications (tamoxifen, e.g.) that are prescribed to treat osteoporosis. Vitamin D is often prescribed with these medications when joint pain occurs, and the same treatment seems to work for resveratrol.

#18 capsun

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Posted 09 February 2011 - 04:37 AM

If it did indeed slow healing, this is probably a good thing (if it's due to the CR-mimetic gene expression). Again, this is why (for instance) mice on resveratrol have greater bone health when they are older. The resveratrol slows bone turnover (and thus osteoporosis). Of course, if you're getting injured all the time, it's a not-so-good thing.

Resveratrol slows bone turnover? Does it inhibit resorption? Or does it enhance bone formation, or perhaps both? Where did you run across this?


Right Here. I've uploaded it as BoneMineralDensity.pdf.

Effects of Resveratrol on Bone Mineral Density in Ovarectomized Rats.

...

In conclusion, the present study demonstrated
that a daily resvertrol intake in adult ovariecto-
mized rats reduced bone turnover and also reverse
a previous bone loss. Furthermore, it appeared that
the highest 45 mg⋅kg-1⋅d-1 resveratrol administration
levels were more effective in depressing the ovari-
ectomy-induced increase in bone turnover (and
in bone resorption specifically) than other dose.
Therefore, ingestion levels of resveratrol should be
considered to improve bone health in a preventive
rather than a curative approach of human postmeno-
pausal osteoporosis.


It seems to inhibit resorption and promote osteoblast production, to the extent that both remain within normal limits. Maxwatt posted some interesting studies. You might find the second pdf interesting, too.

Attached Files



#19 nowayout

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Posted 10 February 2011 - 12:48 AM

What we believe is happening, is that resveratrol does show sufficient anti-aromatase activity to result in symptoms of joint or tendon pain, similar to that in anti-aromatase medications (tamoxifen, e.g.) that are prescribed to treat osteoporosis. Vitamin D is often prescribed with these medications when joint pain occurs, and the same treatment seems to work for resveratrol.


Tamoxifen is a SERM, not an anti-aromatase, and neither SERMs nor anti-aromatases are used to treat osteoporosis, but rather estrogen-sensitive cancers. It is true that some people get joint pain from anti-aromatase drugs or SERMs, but this occurs at very estrogen-suppressive doses. Resveratrol is a very weak anti-aromatase and it would be surprising if it could suppress estrogen enough to cause joint pain, although I guess it is possible. However, anti-aromatase and SERM drugs tend to cause joint clicking (dry joints) and joint pain, but not tendon pain AFAIK, whereas the complaints of many resveratrol users tend to involve tendon pain more. So I suspect the symptoms are somewhat different.

Do you have any source re. the coprescription of vitamin D for SERM or anti-aromatase joint pain? I've never heard of it, and I can't imagine how vitamin D would help a problem caused by too little estrogen.

If resveratrol indeed inhibits healing, for example by inhibiting platelet activity or disrupting the regulation of angiogenesis, to me that would be a more convincing explanation of the tendinitis, especially since most of the complaints are from people who exercise, whereas sedentary resveratrol users seem to seldom complain of tendon pain.

Edited by viveutvivas, 10 February 2011 - 12:53 AM.


#20 maxwatt

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Posted 10 February 2011 - 02:30 AM

Ooops. Tamoxofen is indeed a SERM, as may be resveratrol. I don't have reports of Vitamin D vis a vis Tamoxifen induced arthalgia (joint pain) which has been reported to occur with generic Tamoxifen, but not with the patented drug. Anti-aromatase therapy is frequently an adjuvant or replacement therapy for Tamoxifen, and joint or muscle pain if a frequently reported side effect, one that seems to be coorelated with hydroxy D-25 status.

....
Do you have any source re. the coprescription of vitamin D for SERM or anti-aromatase joint pain? I've never heard of it, and I can't imagine how vitamin D would help a problem caused by too little estrogen.


Here's one:

Cancer Nurs. 2009 Mar-Apr;32(2):143-50.
Vitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapy.
Waltman NL, Ott CD, Twiss JJ, Gross GJ, Lindsey AM.

College of Nursing, University of Nebraska Medical Center, Lincoln, NE, USA.
Abstract
Breast cancer survivors (BCSs) on aromatase inhibitor (AI) therapy often experience musculoskeletal symptoms (joint pain and stiffness, bone and muscle pain, and muscle weakness), and these musculoskeletal symptoms may be related to low serum levels of vitamin D. The primary purpose of this pilot exploratory study was to determine whether serum levels of 25-hydroxyvitamin D (25[OH]D) concentration were below normal (<30 ng/mL) in 29 BCSs on AI therapy and if musculoskeletal symptoms were related to these low vitamin D levels. The mean (SD) serum 25(OH)D level was 25.62 (4.93) ng/mL; 86% (n = 25) had levels below 30 ng/mL. Patients reported muscle pain in the neck and back, and there was a significant inverse correlation between pain intensity and serum 25(OH)D levels (r = -0.422; P < .05 [2 tailed]). This sample of BCSs taking AIs had below normal levels of serum 25(OH)D despite vitamin D supplements. This is one of the few studies to document a significant relationship between vitamin D levels and muscle pain in BCSs on AI therapy. Findings from this pilot study can be used to inform future studies examining musculoskeletal symptoms in BCSs on AI therapy and relationships with low serum levels of vitamin D.

PMID: 19125120

If resveratrol indeed inhibits healing, for example by inhibiting platelet activity or disrupting the regulation of angiogenesis, to me that would be a more convincing explanation of the tendinitis, especially since most of the complaints are from people who exercise, whereas sedentary resveratrol users seem to seldom complain of tendon pain.

We've had non-exercisers complain of such pain, and exercisers who did not experience such pain. Moreover, improving vitamin D status has alleviated such pain in many of those who reported it.

Resveratrol has an IC50 of 80 microM (PMID: 20558073) which would categorize it as a weak aromatase inhibitor, weaker by a factor of ten compared to more effective compounds. However, resveratrol is converted in vivo to piceatannol by the cytochrome P450 enzyme CYP1B1.( PMID: 11875742 ) Piceatannol has much stronger activity than resveratrol by several measures, including anti cancer-activity and SIRT1 activation. I do not know Piceatannol's IC50 as an aromatase inhibitor, but it might account for some of what we are seeing. If anyone can find it, I'd be interested in seeing it. Different reactions to reseratrol may also be due to genetic polymorphisms such that the enzyme is more or less efficient in different people.

A good many body building sites seem to think resveratrol is a potent enough anti-aromatase to recommend it. Not the most reliable endorsement, true, but their anecdotal reports are sometimes accurate.

Edited by maxwatt, 10 February 2011 - 02:31 AM.


#21 malbecman

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Posted 10 February 2011 - 08:04 PM

Anti-aromatase or SERM, resveratrol has been shown to have positive effects on testosterone and sperm counts in rats.


© 2005 The American Society for Nutritional Sciences J. Nutr. 135:757-760, April 2005
Nutrient Metabolism

trans-Resveratrol, a Natural Antioxidant from Grapes, Increases Sperm Output in Healthy Rats1
M. Emília Juan, Eulalia González-Pons, Thais Munuera, Joan Ballester*, Joan E. Rodríguez-Gil* and Joana M. Planas2
Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, E-08028 Barcelona, Spain and; * Unit of Reproducció Animal, Department of Medicina i Cirurgia Animal, Universitat Autònoma de Barcelona, Bellaterra, Spain


ABSTRACT

trans-Resveratrol was reported to have health benefits including anticarcinogenic effects and protection against cardiovascular disease. One of the mechanisms by which it exerts its action is through modulating the estrogen response systems. Because estrogen is involved in male reproductive biology, we investigated the effect of trans-resveratrol on testis and spermatogenesis. Adult male rats were divided into 2 groups. The treated group was administered by gavage 20 mg/(kg · d) of trans-resveratrol suspended in 10 g/L of carboxymethylcellulose for 90 d, whereas the control group received only carboxymethylcellulose during the same period. The relative weight of testes did not differ between the groups. However, the diameter of the seminiferous tubules was significantly reduced from 437.5 ± 0.1 µm in the controls to 310.9 ± 0.1 µm in the resveratrol–treated rats. This decrease was accompanied by a significant increase in tubular density, from 3.20 ± 0.18 in controls to 6.58 ± 0.18 tubules/mm2 in the treated group. Moreover, sperm counts were significantly greater in the resveratrol-treated rats (24.8 ± 3.30 x 107) than in the control group (14.1 ± 0.80 x 107), but sperm quality did not differ. Serum concentrations of gonadotrophins and testosterone were significantly higher in the resveratrol-treated group. We identified a novel activity of trans-resveratrol. The daily oral administration of this phytochemical to adult male rats enhanced sperm production by stimulating the hypothalamic-pituitary-gonadal axis, without inducing adverse effects.
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#22 malbecman

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Posted 10 February 2011 - 10:03 PM

.....and here is another more recent study in mice, it definitely has some androgenic activity.


Arch Pharm Res. 2008 Jan;31(1):83-7.
trans-Resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo.
Shin S, Jeon JH, Park D, Jang MJ, Choi JH, Choi BH, Joo SS, Nahm SS, Kim JC, Kim YB.
College of Veterinary Medicine, Chungbuk National University, Heungdeok-gu, Cheongju, Chungbuk 361-763, Korea.
Abstract

We examined the effects of trans-resveratrol on male reproductive functions; ex-vivo penile erection and in-vivo sperm counts and quality. For the ex-vivo study, the relaxation effects of resveratrol on isolated New Zealand white rabbit corpus cavernosum, precontracted by phenylephrine (5x10(-5) M) were measured. The in-vivo study measured reproductive organ weights, blood testosterone levels, testicular histopathology, sperm counts, as well as the epididymal sperm motility and deformity of male ICR mice given an oral dose of resveratrol (50 mg/ kg) for 28 days. Resveratrol elicited a concentration-dependent relaxing effect on corpus cavernosum, leading to a median effective concentration (EC50) of 0.29 mg/mL. Repeated treatment with resveratrol (50 mg/kg) did not cause an increase in body weight, reproductive organ weight or testicular microscopic findings; however, resveratrol did elicit an increase in blood testosterone concentration, testicular sperm counts and epididymal sperm motility by 51.6%, 15.8% and 23.3%, respectively, without influence on sperm deformity. In conclusion, we propose that resveratrol has a positive effect on male reproductive function by triggering a penile erection, as well as enhancing blood testosterone levels, testicular sperm counts, and epididymal sperm motility.

#23 bentl

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Posted 11 February 2011 - 07:08 PM

Hello SmithX,

One caveat is that I have Lymes which complicates the issue. I am supplementing with Vitamin D3 because I am deficient in Vitamin D.


Just some anecdotal evidence here... My girlfriend has Lyme and continued to have major joint pain after 2 rounds of antibiotics. After reading about ketogenic diets for treating cancer, and how Lyme loves glucose, she went on a ketogenic calorie restricted diet for 10 days (less than 400 cal of protein and fat per day which, to keep things simple, she accomplised by eating 4 eggs a day plus water, and nothing else) to see what it would do to the Lyme. All pain stopped within 4 days. She is pain free as long as she eats a diet low enough in carbs to keep her in mild ketosis. We also raised her D3 serum levels to the 80+ range which, in her case, requires about 15,000 iu per day. Our best guess is that the Lyme spirochetes go dormant without adequate glucose, but they get active again if she eats excessive carbs.

Edited by bentl, 11 February 2011 - 07:09 PM.


#24 maxwatt

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Posted 11 February 2011 - 07:20 PM

Hello SmithX,

One caveat is that I have Lymes which complicates the issue. I am supplementing with Vitamin D3 because I am deficient in Vitamin D.


Just some anecdotal evidence here... My girlfriend has Lyme and continued to have major joint pain after 2 rounds of antibiotics. After reading about ketogenic diets for treating cancer, and how Lyme loves glucose, she went on a ketogenic calorie restricted diet for 10 days (less than 400 cal of protein and fat per day which, to keep things simple, she accomplised by eating 4 eggs a day plus water, and nothing else) to see what it would do to the Lyme. All pain stopped within 4 days. She is pain free as long as she eats a diet low enough in carbs to keep her in mild ketosis. We also raised her D3 serum levels to the 80+ range which, in her case, requires about 15,000 iu per day. Our best guess is that the Lyme spirochetes go dormant without adequate glucose, but they get active again if she eats excessive carbs.

Interesting. One would think a glucose lowering medication such as metformin would help. Myricetin also lowers blood glucose; I think beyond-a-century dot com or iherb sell it.

#25 smithx

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Posted 17 February 2011 - 10:37 AM

Smithx - how are your 25-hydroxy vitamin D levels?


I don't think they're low. They were a bit low 2 years ago when last tested. At the time I was only taking 400IU a day, but since then I upped the dose to 2000IU of D3, and then to 5000IU for at least the last year or more.

The spine injury was about 9 months ago.

Edited by smithx, 17 February 2011 - 10:40 AM.


#26 smithx

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Posted 17 February 2011 - 10:39 AM

Here's a thought. Resveratrol upregulates Superoxide dismutase. All of them. That means it's "chelating" or using up zinc, copper Could it be that you're not getting enough of these in your diet to maintain the activity of reveratrol ?


I took zinc and copper supplements, and had both levels checked (copper via ceruloplasmin). Both were in high-normal range.

#27 smithx

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Posted 17 February 2011 - 10:45 AM

If resveratrol indeed inhibits healing, for example by inhibiting platelet activity or disrupting the regulation of angiogenesis, to me that would be a more convincing explanation of the tendinitis, especially since most of the complaints are from people who exercise, whereas sedentary resveratrol users seem to seldom complain of tendon pain.


I think that a number of compounds which affect the connective tissue are not widely known to do so because most people don't perform strenuous exercise and so are not stressing that tissue.

I have done high intensity sports for many years, and this has made me vulnerable to any weakening or reduction in healing of connective tissue. For instance, I can't take cipro because it makes my ligaments weak. This is a known, but rare side-effect of cipro, but I propose that it may be rare because most people don't notice it.

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#28 bentl

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Posted 10 April 2011 - 01:01 AM

I found a survey article that lists dosage and effects from different studies. It is free to download.

Details posted here:
http://www.longecity...535#entry459535




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