25 replies to this topic

[geo12the]

There used to be a thread I contributed to about resveratrol and joint and tendon issues. I can't find the thread and the search function here has been really SLOW and glitchy so I am starting a new one.

I was wondering if people have any updates on this issue they can share? I do. Long story short:

• we started experiencing tendon issues after supplementing with resveratrol for over 1 year. We were taking highly purified (99%) resveratrol, not the 50% stuff. I could hear my back make weird popping sounds. We both got shoulder tendinitis. My partner got it so bad the doc he was seeing wanted to do surgery. He almost had surgery until he got a second opinion. He did not have surgery thank God.
• About a year ago we switched to taking synthetic resveratrol supplements. And the tendon issues have all but disappeared. Now that I am saying that I hope I don't jinx us.

I remember someone saying that tendon issues caused by resrveratrol might be linked to quinones from Knotweed (the plant they use to purify resveratrol from for supplements) that contaminate the preparations. My own personal belief from our experience is that there definitely is a contaminant in the purified knotweed resveratrol that is harmful to tendons. I wonder if anyone else has any updates from their own experiences?

[MizTen]

This is pretty interesting. I've taken a superfood supplement for about 3 years, Midori Greens, which has knotweed in it. All was well.
Then I added another supplement with resveratrol and a bulk resveratrol. About 2 months after starting the bulk resveratrol I developed tendonitis in my ankles. Never had tendonitis in my life and wasn't doing anything different in the way of exercise before this happened.

[maxwatt]

What dose of these preparations are you guys taking, and what time of day? Also, were joint/tendon issues more prominent in cold weather? Do you know your vitamin D3 status (hudroxy D25 test)?

[geo12the]

What dose of these preparations are you guys taking, and what time of day? Also, were joint/tendon issues more prominent in cold weather? Do you know your vitamin D3 status (hudroxy D25 test)?

We are taking ResVida 100 mg every morning. This resveratrol is synthesized and not plant derived.

Tendon issues did not seem to be related to time of year. Have not had my vitamin D tested but we regularly take Vitamin D and Conzyme Q (we were also taking them back when we were taking the knotweed derived resveratrol).

One other factor is that the dose of resveratrol is lower than when we were taking plant derived resveratrol which was 250mg. So the lower dose could also be a factor. But I believe there is something in the knotweed derived resveratrol that is harmful for tendons after you take it for a while.

[zorba990]

I can't find any information about how resvida is made, what bulk powder pricing is, etc. There are plentiful sources of 99% tRes plant derived powders with more known about what is in the other 1% So this seems a little suspect.
Gonna stick with megaresveratrol as no tendon issues there.

[geo12the]

I can't find any information about how resvida is made

DSM has a patent for synthesizing resveratol in the lab. This is from their website:

http://www.dsm.com/m...ls/resvida.html

[hav]

What dose of these preparations are you guys taking, and what time of day? Also, were joint/tendon issues more prominent in cold weather? Do you know your vitamin D3 status (hudroxy D25 test)?

We are taking ResVida 100 mg every morning. This resveratrol is synthesized and not plant derived.

Tendon issues did not seem to be related to time of year. Have not had my vitamin D tested but we regularly take Vitamin D and Conzyme Q (we were also taking them back when we were taking the knotweed derived resveratrol).

One other factor is that the dose of resveratrol is lower than when we were taking plant derived resveratrol which was 250mg. So the lower dose could also be a factor. But I believe there is something in the knotweed derived resveratrol that is harmful for tendons after you take it for a while.

Curious what specific brand the other 250 mg resveratrol you used to take was. I only ask because there might have been more than 99% pure resveratrol in the capsule with it. Is the ResVita 100 mg you take now a soft-gel containing this?

Extra virgin olive oil, gelatin, glycerin, yellow bees wax, purified water, soy lecithin and annatto extract in sunflower oil.

Howard

[geo12the]

Curious what specific brand the other 250 mg resveratrol you used to take was.

I would rather not say. The producer seems a bit intense and is on this forum and I don't want to get into a war with him. Perhaps that information answers the question.

Is the ResVita 100 mg you take now a soft-gel containing this?

Yes

[zorba990]

I can't find any information about how resvida is made

DSM has a patent for synthesizing resveratol in the lab. This is from their website:

http://www.dsm.com/m...ls/resvida.html

Do you have the patent number? Their site doesn't give any information about what the synthesis process might be. Such processes can be equally problematic where solvents and other toxins are concerned as with a naturally derived product. I'm not seeing the advantage over tested 99% Res from plant material.

[geo12the]

I can't find any information about how resvida is made

DSM has a patent for synthesizing resveratol in the lab. This is from their website:

http://www.dsm.com/m...ls/resvida.html

Do you have the patent number? Their site doesn't give any information about what the synthesis process might be. Such processes can be equally problematic where solvents and other toxins are concerned as with a naturally derived product. I'm not seeing the advantage over tested 99% Res from plant material.

WO 2012080120 A1

If the purification and QC are not good I agree there are concerns.

[hav]

Curious what specific brand the other 250 mg resveratrol you used to take was.

I would rather not say. The producer seems a bit intense and is on this forum and I don't want to get into a war with him. Perhaps that information answers the question.

Is the ResVita 100 mg you take now a soft-gel containing this?

Yes

I understand. But if the 250 mg product is the one I think it is, it is optimized for rapid delivery to the liver, and from there directly to the bloodstream at maximized peak levels. I believe resveratrol is normally absorbed through that same pathway but adding polysorbate and/or mct oil boosts absorption through that pathway even more. As opposed to the ResVita product which uses olive oil and lecithin which would instead optimize uptake to bypass the liver on the 1st pass and reach the bloodstream in much lesser amounts after primary absorption in the lymphatic system. The tendon/joint effect you experienced, which is not typical but not uncommon either, may possibly be related to that difference in delivery paths.

Another possibility is an unusual sensitivity to polysorbate. In a toxicity study in rats and mice, inflammation was observed, but only at extremely high dosages. Polysorbate's in allot of stuff, however, so if you were allergic to it or something, you'd probably be well aware of it.

Howard

[maxwatt]

For the groups' information, there are several compounds found in knotweed, which may be though present in only trace amounts in a purified 98% or 99% extract, may still reach levels sufficient to have a physiological effect of some sort.

Besides resveratrol, other substances in knotweed are: Polydatin, Physcion ,Emodin, various anthraquinones, other stilbenes, flavonoids, naphthoquinone, and polysaccharides.
Among the anthraquinones, we find chinone, and emodin, but also chrysophanol, rhein, physcion, questin & fallacinol.
the anthraquinonic glycosides are mainly physcion-8-ß-D-glucoside & emodin-8-ß-D-glucoside.
Polygonum Flavonoids include glucofrangulin, quercetin, quercetin-3-arabinoside,quercetin –3 - rhamnoside,
quercetin – 3 - glucoside, quercetin-3-galactoside, luteolin-7-glucoside & three kinds of derivatives of protocatechuic acid, (+)-catechin,
2,5-dimethyl-7-hydroxychromone apigenin.
not to mention Naphthoquinone & anthraquinonic glycoside
There is 2-methoxy-6-acetylmethyljuglone & torachrysone – 8 – O – D - glucoside found in the naphthoquinone & anthraquinonic glycoside, that are isolated from Polygonum.
Also 7 – hydroxy – 4 – methoxy – 5 - methylcoumarin.

If anyone researc=hes these and finds a correlation to joint pain, let us know.

IF taking 250 milligrams of 98 or 99% extract, some of these can reach levels of several milligrams; enough to have an effect where there is a sensitivity. And the amount of any of these compounds can vary from batch to batch. Much of the synthetic resveratrol on the market is not the product of a chemical synthesis from pure precursor ingredients, but is produced by bacteria grown in vats in Shanghai or vicinity. Or in Germany. What impurities these might or might not have I cannot say.

[hav]

Got the most hits in pubmed on resveratrol, emodin, quercetin, luteolin, catechin, and naphthoquinone... to treat arthritis. Also got a few on Rhein, again as a possible treatment. Nothing suggesting any of those would have a negative effect on joints.

But in relation to tendon health, I came across this, which I'm not sure I understand:

Flavonoids inhibit the formation of the cross-linking AGE pentosidine in collagen incubated with glucose, according to their structure.

Monomeric flavonoids (25 and 250 microM) markedly reduced pentosidine/hydroxyproline values in a concentration- and structure-dependent manner. In decreasing order of their specific inhibitory activity, they rank as follows: myricetin > or = quercetin > rutin > (+)catechin > kaempferol. Thus 3'-OH or 4-oxo + Delta(2-3) increase the inhibitory activity; conjugation by Rha-Glc on 3-OH decreases it. Procyanidin oligomers from grape seed were more active than pine bark procyanidin oligomers: this may be related to the galloyl residues present in grape seed oligomers only. Procyanidin oligomers are known to be cleaved into monomers in the gastric milieu and monomeric flavonoids to be absorbed and recovered at micromolar concentrations (with a long plasmatic half-life) in extracellular fluids, in contact with collagens.

I've read that pentosidine/hydroxyproline levels have something to do with tendon health but I'm not clear if reducing it is good or bad. FWTW, I'm under the impression that procyanidins are good for tendon health.

Howard

[maxwatt]

Pentosidine cross-links are considered bad. Gives wrinkles in skin if I remember, makes tendons stiff and less resilient. And flavonoids only inhibit, not reverse cross-links. So I do not see how they could contribute to tendon pain.

Perhaps their is an immune systimulation stimulation, such that the body attacks its own tendons? This is possible, but speculative.

[hav]

What confuses me about Pentosidine is that in this study, they found a decrease in amount detected in degenerated human supraspinatus (ST-N) but not in biceps brachii tendons (BT-N) which apparently remained relatively normal with aging:

Lysylhydroxylation and non-reducible crosslinking of human supraspinatus tendon collagen

In BT-N, tendons that served as control tissue as it shows rarely matrix abnormalities, pentosidine levels rise linearly with age (20-90 years), indicating little tissue remodelling (resulting in an undisturbed accumulation of pentosidine). A similar accumulation was observed in ST-N up to 50 years. At older ages, little pentosidine accumulation was observed and pentosidine levels showed large interindividual variability. This was interpreted as remodelling of collagen in normal ST after age 50 years because of microruptures (thus diluting old collagen with newly synthesised collagen). All degenerate ST samples showed decreased pentosidine levels compared with age matched controls, indicating extensive remodelling in an attempt to repair the tendon defect.

They seem to be pointing to decreased pentosidine levels as a marker for damaged tendon and a remodelling effort to repair it. I realize that the point of their conclusion is that remodelled tendon may be weaker... but maybe if already low pentosidine levels get forced even lower, it causes more damage. Or inhibits any repair. Suggesting that quercetin and catechin resveratrol impurities could have a negative effect on tendon health if tendons are trying to repair themselves.

Does that flavinoid study say that Procyanidins decrease pentosidine inhibition because of their "conjugation by Rha-Glc on 3-OH?" I had a tendon issue myself that I treated with a 6-week course of TB500 and have been loading up on procyanidins and resveratrol for the last 2 months since then and have not had a relapse.

Howard

[maxwatt]

Sounds like the more damage to the ST, the more repair with fresh collagen, thus the lower the pentosidine levels in the tendon as a whole. Suggests stressing the tendons will keep them regenerating and effectively younger. Score one for weight-lifting?

Edited by maxwatt, 15 December 2013 - 08:40 PM.

[Jembe]

I have two unopened bottles of LEF "Optimized Resveratrol". Haven't tried it yet, but when I started taking Letrozole, my joint pains went down. So I'm a little skeptical about the aromatase inhibitor theory of resveratrol-caused joint pain. I'm pretty darn sure Letrozole does a better job at lowering estradiol than resveratrol.

[cudBwrong]

In vitro, resveratrol protects against tendonitis.

(Free full text)

http://www.ncbi.nlm....les/PMC3406664/

J Biol Chem. 2012 July 27; 287(31): 25770–25781.
Published online 2012 June 11. doi: 10.1074/jbc.M112.355420


PMCID: PMC3406664
Sirt-1 Is Required for the Inhibition of Apoptosis and Inflammatory Responses in Human Tenocytes


Franziska Busch,^‡ Ali Mobasheri,^§ Parviz Shayan,^¶ Ralf Stahlmann,^‖ and Mehdi Shakibaei^‡,1


From the ^‡Institute of Anatomy, Ludwig-Maximilians-University Munich, Munich 80336 Germany,
^§School of Veterinary Medicine and Science, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, United Kingdom,
^¶Investigating Institute of Molecular Biological System Transfer, 1417863171 Tehran, Iran, and
^‖Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin 13353, Germany
¹ To whom correspondence should be addressed: Institute of Anatomy, Musculoskeletal Research Group, Ludwig-Maximilian-University Munich, Pettenkoferstrasse 11, 80336 Munich, Germany., Tel.: Phone: 49-89-5160-4827; Fax: 49-89-5160-4828; E-mail: mehdi.shakibaei@med.uni-muenchen.de.
Author information ▼ Article notes ► Copyright and License information ►


This article has been cited by other articles in PMC.
Go to:
Abstract


Tendon overuse injuries and tendinitis are accompanied by catabolic processes and apoptosis of tenocytes. However, the precise molecular mechanisms of the destructive processes in tendon are not fully understood. Sirt-1, a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, has been linked to transcriptional silencing and appears to play a key role in inflammation. The purpose of this study was to examine whether down-regulation of Sirt-1 using antisense oligonucleotides (ASO) affects inflammatory and apoptotic signaling in tenocytes. Transient transfection of tenocytes with ASO against Sirt-1 induced expression of Bax and other proteins involved in apoptosis (cleaved caspase-3 and poly(ADP-ribose)polymerase), acetylation of tumor suppressor p53, and mitochondrial degradation. Interestingly, Sirt-1 was found to interact directly with p53. In contrast, Sirt-1 activator resveratrol inhibited interleukin-1β (IL-1β)- and nicotinamide-induced NF-κB activation and p65 acetylation and suppressed the activation of IκB-α kinase. Resveratrol also reversed the IL-1β- or nicotinamide-induced up-regulation of various gene products that mediate inflammation (cyclooxygenase-2) and matrix degradation (matrix metalloproteinase-9) that are known to be regulated by NF-κB. Knockdown of Sirt-1 by using ASO abolished the inhibitory effects of resveratrol on inflammatory and apoptotic signaling including Akt activation and SCAX suppression. Down-regulation of histone deacetylase Sirt-1 by mRNA interference abrogated the effect of resveratrol on NF-κB suppression, thus highlighting the crucial homeostatic role of this enzyme. Overall, these results suggest for the first time that Sirt-1 can regulate p53 and NF-κB signaling via deacetylation, demonstrating a novel role for resveratrol in the treatment of tendinitis/tendinopathy.

I think the suspicion that some impurity or additive is the causative agent of the inflammation may be correct.

It makes sense to try switching brands, (as the original poster did,) in a case like this. It doesn't mean that the supplier is bad; so many things can go wrong in a long supply chain, with the result being a slightly inferior batch, or part of a batch. It might slip past whatever quality control procedures are in place, even if the vendor follows pretty good practices. We've seen plenty of quality problems, even with "name brand" drugs, especially in the OTC market.

There are affordability limits to the amount of testing you can do. That's why the laboratory reagents cost so much.

Edited by cudBwrong, 09 January 2014 - 03:18 PM.

[AlexCanada]

My joint pains subsided slightly but now becoming very prominent after a 125mg dose from a 600mg "blend'' formula of Resveratrol Forte from Ezymatic. It contains knotweed just like the Natural factors Resveratrol I tried before. Both help my mood immensely. The positive effects are priceless but both brands cause me serious joint pains which I have never before experienced in my life. What might be a good brand to try which does not contain any knotweed? Additionally I added Selenium to my doses and it does not help! It only helps my body temperature not reach very cold levels...

Edited by AlexCanada, 15 January 2014 - 11:09 AM.

[cudBwrong]

My joint pains subsided slightly but now becoming very prominent after a 125mg dose from a 600mg "blend'' formula of Resveratrol Forte from Ezymatic. It contains knotweed just like the Natural factors Resveratrol I tried before. Both help my mood immensely. The positive effects are priceless but both brands cause me serious joint pains which I have never before experienced in my life. What might be a good brand to try which does not contain any knotweed? Additionally I added Selenium to my doses and it does not help! It only helps my body temperature not reach very cold levels...

I suggest that you look for a brand that advertises a high purity level of trans-resveratrol, as confirmed by an independent lab. Some vendors will publish a recent certificate of analysis (COA) as documentation of what you are buying.

I don't think that knotweed itself is an issue. It is a common source material, because it contains a lot of resveratrol, so it is cost-efficient to use it. If the product is purified to 98 or 99% resveratrol, then the original source doesn't matter so much.

The problem I have taking a "proprietary resveratrol blend" with some unknown combination of ingredients is that I don't know what I'm taking and I can't control the variables.

Look through some of the threads on this forum, and/or search on something like "pure resveratrol." Read the fine print. One of the products with "pure" in its name is only 20 per cent resveratrol.

Resveratrol comes in 2 isomers, (highly similar chemical structures,) "cis" and "trans." It is the "trans" form which has been studied for its biological effects.

[geo12the]

My joint pains subsided slightly but now becoming very prominent after a 125mg dose from a 600mg "blend'' formula of Resveratrol Forte from Ezymatic. It contains knotweed just like the Natural factors Resveratrol I tried before. Both help my mood immensely. The positive effects are priceless but both brands cause me serious joint pains which I have never before experienced in my life. What might be a good brand to try which does not contain any knotweed? Additionally I added Selenium to my doses and it does not help! It only helps my body temperature not reach very cold levels...

I tried a few different resveratrol formulations from %50 all the way to super highly purified (%99percent or whatever). All gave me and my partner tendon issues to the point where my partner almost had surgery (he did not thank God). All problems vanished after we switched to ResVida 100mg Double-Strength Resveratrol (got it on Amazon). This is a synthetic form of resveratrol. I suggest you try it and report back. Based on my experience I am certain you tendon issues will go away.

[geo12the]

I don't think that knotweed itself is an issue. It is a common source material, because it contains a lot of resveratrol, so it is cost-efficient to use it. If the product is purified to 98 or 99% resveratrol, then the original source doesn't matter so much.

Based on my experience I am convinced the knotweed is the issue. My partner and I had terrible symptoms using highly purified resveratrol (99% confimed by an independent lab etc.). Knotweed is known to have quinolones and these are known to cause tendon issues (for example Cipro makes people more susceptible to Achilles tendon ripping). Enough quinolones could be present in the 99% formulations that they are causing these problems.

Edited by geo12the, 15 January 2014 - 06:49 PM.

[cudBwrong]

Based on my experience I am convinced the knotweed is the issue. My partner and I had terrible symptoms using highly purified resveratrol (99% confimed by an independent lab etc.). Knotweed is known to have quinolones and these are known to cause tendon issues (for example Cipro makes people more susceptible to Achilles tendon ripping). Enough quinolones could be present in the 99% formulations that they are causing these problems.

I have no doubt of geo12the's reports of tendon problems, and I think that the synthetic product (ResVida) would remove any doubts about the remaining 1% of impurities. Certainly there could be something in those impurities causing a problem, although I have not had any joint or tendon issues after years of use of a 99% product.

The one question I have for geo12the is the report that knotweed contains quinolones. I have not been able to document this. I know that certain plants, such as Samento, the South American variety of Cat's Claw, have quinovic acid gylcosides, which are related to the synthetic quinolones such as Cipro. Samento has been reported to cause joint pain in some patients, as has Cipro. But I haven't seen a report of quinovic acid gylcosides in knotweed.

There is a similar-sounding substance in knotweed which is a secondary metabolite of resveratrol, 2-methoxy-6-acetyl-7-methyljuglone, which is a variety of naphthoquinone, but that is not associated with joint pain. Also emodin, found in knotweed, is an anthraquinone, but again, not associated with joint pain. Juglone has been reported to inhibit joint pain:

http://www.jimmunol....83/10/6689.long

There is a previous thread which speculates on whether emodin causes symptoms similar to quinolones:

http://www.longecity...ing-quinolones/

But I don't see any reports of this in the literature. Just the opposite, emodin has been used to suppress joint inflammation:

http://www.ncbi.nlm....pubmed/23685361

http://www.ncbi.nlm....pubmed/21881229

It's possible that in some people, emodin may have an opposite effect. If that is true, then there is your answer. A significant portion of those 1% of impurities is going to be emodin, which is why I'm suspicious that it may be the cause for those people who have a bad reaction to a 99% product.

In short, I'm sure there is something going on, but it may not be due to a quinolone.

Edited by cudBwrong, 15 January 2014 - 08:08 PM.

[geo12the]

The one question I have for geo12the is the report that knotweed contains quinolones.

There are abstracts that mention emodin and physcion which are anthraquinones related to quinolones. I think that the problem is that a lot of it is unknown and has not been studied. There are lots of studies that document the negative effects on tendons of cipro because its a prescribed drug more commonly used than resveratrol. We are guinea pigs. And some of us may be more sensitive than others to the effects of whatever is in that 1% that is not resveratrol in the %99 percent supplements.






J Agric Food Chem. 2013 Jul 3;61(26):6383-92. doi: 10.1021/jf4019239. Epub 2013 Jun 19.
Quality assessment of Japanese knotweed (Fallopia japonica) grown on Prince Edward Island as a source of resveratrol.

Chen H, Tuck T, Ji X, Zhou X, Kelly G, Cuerrier A, Zhang J.

Author information

• Aquatic and Crop Resource Development, National Research Council Canada, 550 University Avenue, Charlottetown, PE C1A 4P3, Canada.

Abstract


Japanese knotweed (Fallopia japonica , also known as Polygonum cuspidatum) is a common invasive plant species on Prince Edward Island (PEI), Canada, whereas it has been used in Chinese medicine and more recently as a raw material for extracting resveratrol. This paper reports on the quantification of resveratrol, polydatin, emodin, and physcion in roots, stems, and leaves of Japanese knotweed samples from PEI and British Columbia (BC), Canada, and nine provinces of China, by ultraperformance liquid chromatography (UPLC). The results showed that the root contains a much higher level of resveratrol than the stem and leaf, and it is accumulated in its highest level in October. PEI-grown knotweed contains similar levels of resveratrol and polydatin compared to Chinese samples collected in the month of October, but the contents of the other anthraquinones (emodin and physcion) are different. As such, Japanese knotweed grown in PEI could be a commercially viable source of raw material for resveratrol production; however, caution has to be taken in harvesting the right plant species.

[cudBwrong]

geo12the, thanks for replying, your link is similar to the reports I've seen. Anthraquinones like emodin have some structural similarity to the quinolones, but it's not known if they cause the same kind of joint or tendon problems. Emodin is pretty widely used, even more so than resveratrol. It is one of the main active ingredients in the stimulant laxative Senokot, which also contains other plant derived anthraquinones similar to emodin. Joint pain is reported as a rare side effect of Senokot.

The senna plants, which give Senokot its name, are remotely related to the knotweeds. In fact, Resveratrol was first isolated from a senna. They are both eudicots, with three grooves in their pollen, which indicates they have a weak evolutionary relationship.

Drugs have different effects on different people; even drugs which get extensive clinical trials have side effects which show up later. The best course is to be alert, do your research, partner with your doctor, and do what works best for you.

Edited by cudBwrong, 15 January 2014 - 08:38 PM.

[kenj]

In my case, the 50% extract wasn't the culprit. Years ago I dealt with these shitty joint/tendon pains, from 50% and 98+%.

Today I can take 50% with no adverse effects. No clue what happened. Megadose 5-MTHF (folate vitamin) might've helped, but I'm definitely .. not sure. :p