"500 club" 500mg of trans-resveratrol per day
#481
Posted 24 March 2007 - 04:03 AM
#482
Posted 24 March 2007 - 04:05 AM
Ordered SupernutritionUSA's Perfect Blend. Good to know that I will not be inadvertently reversing the effects of my resveratrol supplementation which thus far is going well. The most noted effect seems to be a dramatic increase in aerobic capacity and general increase in well being. The increase in aerobic capacity is very quantifiable, the increase in well being is of course subjective but very noticeable.
Just curious, what was your increase? Are you a runner?
#483
Posted 24 March 2007 - 04:18 AM
#484
Posted 24 March 2007 - 07:08 AM
Stephen
#485
Posted 24 March 2007 - 09:32 AM
IME, although I perceive generally increased stamina, lack of fatigue, resistance to various stressors, and mood elevation, I've not noted any boost in performance WRT resistance exercise. Aerobic/stamina endurance does appear elevated, FWIW, although I've not done any objective quantification of this perceived effect.
#486
Posted 24 March 2007 - 01:35 PM
I'm not aware of published observations during the resveratrol studies regarding the explosiveness of the rat's bowel movements.No explosive bowel movements, no gas, nothing....
#487
Posted 24 March 2007 - 02:40 PM
Sinclair used a much purer lab grade trans resveratrol for his research.I'm not aware of published observations during the resveratrol studies regarding the explosiveness of the rat's bowel movements.No explosive bowel movements, no gas, nothing....
#488
Posted 24 March 2007 - 07:47 PM
I'm not aware of published observations during the resveratrol studies regarding the explosiveness of the rat's bowel movements.No explosive bowel movements, no gas, nothing....
As mentioned numerous times in this forum, it's not the resveratrol but the emodin, a substance present in
Japanese Knotweed, from which most supplemental extract is derived, that causes the GI effects
some folks have experience from higher dose resveratrol (and accompanying emodin) supplementation.
Sinclair's experiments used synthetic, pure (>99%) t-resveratrol. No emodin = no GI effects.
#489
Posted 24 March 2007 - 11:04 PM
I'm not aware of published observations during the resveratrol studies regarding the explosiveness of the rat's bowel movements.No explosive bowel movements, no gas, nothing....
As mentioned numerous times in this forum, it's not the resveratrol but the emodin, a substance present in
Japanese Knotweed, from which most supplemental extract is derived, that causes the GI effects
some folks have experience from higher dose resveratrol (and accompanying emodin) supplementation.
Sinclair's experiments used synthetic, pure (>99%) t-resveratrol. No emodin = no GI effects.
Thanks, but I knew that, I've been reading that numerous times. However, there have been several other in vivo studies in rodent models as well, e.g. here, here, here (possibly) and here. Some of these studies have been performed in 2006 and before. I doubt if the Indian purified / synthesized form of TRES was available at that time. But I don't know. Hence the question.
I have a very dry form of humour, more often misunderstood than appreciated. My question was partly instigated by that as well to be honest.
#490
Posted 25 March 2007 - 12:24 AM
WRT synthetic resveratrol, ISTM it's been produced by chemical companies for some time. Here's a quote from LEF's recent article on resveratrol:
"Grape Seed Extract with Resveratrol
In September 2004, a group of normally fed mice was supplemented with either synthetic resveratrol or grape seed extract with resveratrol obtained from Life Extension. Our objective was to compare gene expression in the livers of the mice in the grape extract group to gene expression in the livers of normally fed and CR mice."
So, it's been available since at least 2004. Very high purity PC extracts, as well as resveratrol extracted from grapes would contain either negligible or no emodin.
But, perhaps this post is merely missing the thrust of your joke.
#491
Posted 25 March 2007 - 01:23 AM
A related issue is that what wonders me in this thread are the short-term observations that seem to prevail the long-term benefits. I'm taking 200mg TRES for about a week now. So I do not belong to the 500mg club. But my metabolism functions in such a way that I have comparable effects with half the supplement dosage than that is used in general for various substances. Anyway, taking 200mg also elevates my mood and "energy" big-time, as also has been reported by others. In the beginning, but still in the 100mg period, I did experience some GI effects that could be described as "explosive". Fortunately, they vanished completely. Individuals (e.g. Duke N. ) using the 99% pure form are stating that the otherwise mentioned short term beneficial effects do not occur on them. Mind raised the hypothesis that people who already have an optimal supplement regime might not experience much additional benefits of TRES on short notice. However, my concern is that the non-TRES part of the resveratrol capsules might be responsible for these short-time effects in stead of the prim airy contents. Which causes me to be cautious; (a) we do not have long-term data on human use of TRES and (b) we are lacking data on the non-TRES contents of the stuff we are taking and data on purity of non-synthetic resveratrol products in general.
Ok, why am I taking it when i'm that pedantic? I do have some auto-immune related issues with some of my joints. The issues are not severe, but tolerable to a certain level. Imuno-suppresive medication is out of order since the symptoms are not that severe to justify the side effects of these treatments. So, TRES is one of my current "experiments". I do not have current data yet on my blood markers for inflammation, but they will be updated in 2 months.
Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway.Sharma S, Chopra K, Kulkarni SK, Agrewala JN.
Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India.
The role of resveratrol and curcumin is well documented in cancer, inflammation, diabetes and various other diseases. However, their immunosuppressive action on T cells, B cells and macrophages is not well documented. In the present study, we have ascertained the effect of resveratrol and curcumin on T and B cells and macrophages. The most striking findings were that both resveratrol and curcumin suppressed the activity of T and B cells and macrophages, as evidenced by significant inhibition in proliferation, antibody production and lymphokine secretion. Interestingly, curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating CTLA-4. Resveratrol also functioned by decreasing the expression of CD28 and CD80, as well as by augmenting the production of interleukin (IL)-10.
PMID: 17177975
Effects of resveratrol in inflammatory arthritis.Elmali N, Baysal O, Harma A, Esenkaya I, Mizrak B.
Department of Orthopaedics and Traumatology, Inonu University Medical Faculty, 44069, Malatya, Turkey, nelmali@hotmail.com.
Nuclear factor kappa B (NF-kappaB), is a pivotal transcription factor involved in the activation of the TNF-alpha and IL-1beta genes. Activation of NF-kappaB in synovial cells is a feature seen in arthritis patients. Resveratrol, a polyphenolic, natural phytoalexin found with particularly high levels in grape skin and red wine is potent and specific inhibitor of TNF-alpha and IL-1beta induced NF-kappaB activation. We aimed to determine the in vivo effects of intra-articular injections of resveratrol on cartilage and synovium in an experimental rabbit inflammatory arthritis model. MATERIALS AND METHODS: Arthritis was induced by intra-articular injection of three times of 50 mug lipopolysaccharide (LPS) at day 0, 4 and 8 at 4-day intervals into the knee joints of rabbits. To the test group, 10 muMol/kg resveratrol in the DMSO was injected in the knees at day 0 and then it was continued once daily for 2 weeks. To the control group the same time and amount of DMSO was injected the knees of rabbits. All rabbits were killed 1 week after the last injection and cartilage tissue and synovium were evaluated with semiquantitative scoring histologically. RESULTS: According to control group in the resveratrol group, significantly decreased cartilage destruction was determined by H&E staining (p = 0.04). Loss of matrix proteoglycan content in the cartilage was much lower, as determined by safranin O staining (p = 0.03). We also observed marked synovial inflammation after intra-articular injection to control knees, but not in the resveratrol treated group knees (p = 0.01). CONCLUSION: This study suggests that intra-articular injection of resveratrol may protect cartilage against the development of experimentally induced IA.
PMID: 17115116
Effect of resveratrol in experimental osteoarthritis in rabbits.Elmali N, Esenkaya I, Harma A, Ertem K, Turkoz Y, Mizrak B.
Department of Orthopaedics and Traumatology, Inonu University Medical Faculty, 44069, Malatya, Turkey. nelmali@hotmail.com
OBJECTIVE: Resveratrol (trans-3,4',5-trihydroxystilbene) is a phytoalexin found in high concentration in the skins of grapes and red wines which has been shown to have antiinflammatory, anticancerogen and antioxidant properties. Resveratrol is a potent and specific inhibitor of nuclear factor kappa B (NF-kappaB). Resveratrol also inhibits COX-2 gene expression and enzyme activity. We aimed to determine the in vivo effects of intra-articular injections of resveratrol on cartilage and synovium in an experimental osteoarthritis (OA) model in rabbits. METHODS: As OA model, rabbits underwent unilateral anterior cruciate ligament transection (ACLT). Five weeks after test group was injected with 10 microMol/kg resveratrol in dimethylsulphoxide (DMSO) in the knees once daily for two weeks and as the control group at the same time DMSO was injected into the knees. All rabbits were killed one week after the last injection. Cartilage tissue and synovium were evaluated with a histological scoring system. RESULTS: Histological evaluation of cartilage tissue by H&E staining revealed a significantly reduced average cartilage tissue destruction score of 1.7 in the resveratrol group versus 2.8 in the control group (p = 0.016). Loss of matrix proteoglycan content in cartilage was also much lower, as determined by safranin O staining. Scores of synovial inflammation didn't show difference between groups (1.3 vs 2.2; p = 0.057). CONCLUSION: A characteristic parameter in arthritis is the progressive loss of articular cartilage. This study suggests that intraarticular injections of resveratrol starting at the onset of disease may protect cartilage against the development of experimentally induced OA.
PMID: 15883738
Inhibition of COX isoforms by nutraceuticals.Seaver B, Smith JR.
University of Montana, 441 S. 6th E., Missoula, MT 59812, USA.
Humans have two isoforms of Prostaglandin H Synthase or cyclooxygenase: COX-1 and COX-2. COX-1 is cytoprotective. COX-2 inhibitors reduce inflammation without the risk of ulceration and kidney damage. The ideal nutraceutical would inhibit COX-2 synthesis while preserving COX-1 synthesis. The hypothesis for this research was that COX inhibitors would fall primarily into three categories: COX-2 specific inhibition, non-specific inhibition (COX-1 and COX-2), and minimal inhibition. The human Cayman COX inhibitor screening assay was used to determine the inhibitory concentration 50 (IC50) of COX-1/ COX-2 activity of each nutraceutical. The assay was run, in duplicate, with three concentrations of a suspected inhibitor, a standard curve of eight concentrations, a non-specific binding sample, and a maximum binding sample. The inhibition and concentration of each sample was then put on a multiple regression best-fit line and the IC50 determined. For comparison, ibuprofen, rofecoxib, naproxen, and indomethacin were used. Positive results were seen for ipriflavone, resveratrol, MSV-60, amentoflavone, ruscus extract and notoginseng. Glucosamine, nexrutine, and berberine did not inhibit either isoform.
PMID: 15364641
Worrying (just a bit):
Potential pro-inflammatory action of resveratrol in vascular smooth muscle cells from normal and diabetic rats.Cignarella A, Minici C, Bolego C, Pinna C, Sanvito P, Gaion RM, Puglisi L.
Department of Pharmacological Sciences, University of Milan, via G. Balzaretti 9, I-20133 Milan, Italy. andrea.cignarella@unimi.it
BACKGROUND AND AIM: Based on the reported cardioprotective effects of resveratrol, a polyphenolic antioxidant abundant in grapes that binds to estrogen receptors, and the well-characterized anti-inflammatory properties of 17beta-estradiol, the effects of resveratrol on the functional expression of inflammatory enzymes were assessed in vascular smooth muscle cells (SMC) from normoglycaemic and streptozotocin-diabetic rats. METHODS AND RESULTS: SMC were isolated from the aorta four weeks after treating rats with streptozotocin or its vehicle. In SMC exposed to a cytokine mixture for 24h, unexpectedly, treatment with resveratrol (0.1-100microM) as well as the structurally related isoflavone genistein (1nM-1microM) enhanced expression of inducible NO synthase (iNOS). Genistein failed to mimic the elevated iNOS activity induced by resveratrol. Inhibition of estrogen receptors by the pure antiestrogen ICI 182,780 reversed the action of resveratrol on iNOS. In addition, resveratrol failed to alter cyclooxygenase-2 protein levels but reduced the accumulation of prostaglandin E(2) in the culture medium of SMC from normoglycaemic, but not diabetic rats. CONCLUSIONS: These results indicate that resveratrol, at concentrations approaching putative peak plasma levels in vivo, exhibited no anti-inflammatory properties in vascular SMC from normal and diabetic rats. By contrast, resveratrol displayed a potential pro-inflammatory activity in settings of vascular inflammation.
PMID: 16829340
Many more of this kind of data available. Insight on the matter would be very much appreciated!
Edited by alterego, 25 March 2007 - 01:34 AM.
#492
Posted 25 March 2007 - 09:24 AM
and accompanying substances.
I do have, and have taken 99%+ pure synthetic t-resv. (limited amount currently.)
Unfortunately for the purpose of discerning whether the mood elevating effects many
t-resv. supplement users have reported, I have also been concurrently using some
PC extract derived t-resv. of various purity (50%-98%), therefore confounding analysis
of my response to the synthetic version by itself.
My own GI issues, while now less dramatic than they were a while ago, remain more
salient than prior to increasing my overall t-resv. supplementation from about 60 mg
- 100 mg/day to approx. 1 gram/day, from mixed sources.
While I'd like to experiment with the subjective effects noted for synthetic vs.
extract, I currently have too little synthetic, IMO, to warrant this program.
If I can acquire additional highly pure synthetic t-resv., I'll give it whirl.
In the meantime, I do enjoy the mood elevation effect, from whatever
substance. Perhaps the "wonder" supplement for humans may not be
t-resv. by itself, but only when accompanied by additional substances
such as grape OPCs, or emodin, or other, yet unidentified substance
accompanying t-resv. in supplement containing t-resv.
Doubtless, eventually, time will tell. In the meantime, we remain
on the edge of the dark unknown (as always, ISTM, no?).
YMMV, and "predictions are hard, especially about the future...."
#493
Posted 25 March 2007 - 04:49 PM
In case the source of the extract would have been only grapes, ok, it would be possible to extrapolate that it is probably safe, with less concern associated. E.g. the basic reasoning being like this: what could be wrong with dealcoholized wine? But since the other source of the extract is the knotweed, I'm still a bit concerned. But I was not able to find any negative evidence. And in case a weed would have psycho-active capabilities suitable for abuse, it would have been common knowledge already.
Furthermore, there are also studies that are carried out with just the knotweed extract, like
Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice.Kimura Y, Okuda H.
PMID: 11385077
Reassuring study:
Constituents from Polygonum cuspidatum.Xiao K, Xuan L, Xu Y, Bai D, Zhong D.
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, People's Republic of China.
Two lignan sulfates, a stilbene derivative and a phenol sulfate, together with 10 known compounds, were isolated from an aqueous extract of the root of Polygonum cuspidatum. The new compounds were elucidated based on chemical evidence and spectroscopic techniques including two-dimensional NMR methods. They exhibited no inhibition of lipid peroxidation and no cytotoxic and DNA cleavage activities.
PMID: 12036013
Ergo, I'm not excessively worried about it.
#494
Posted 25 March 2007 - 09:02 PM
#495
Posted 26 March 2007 - 12:24 AM
Also, resveratrol glycon appears to be more water soluble, but it's not been established to have the same efficacy as t-resveratrol, AFAIK.
#496
Posted 26 March 2007 - 03:00 AM
Since resveratrol is phenolic, it should be possible to ionize it in basic solution. (resveratol pKa = 9.14) It might be possible for the pH of such a solution to be adjusted so that you had a soluble phenoxide anion of resveratrol, but the solution was not so caustic that you couldn't consume it... but why would you want to go to the trouble? Resveratrol is absorbed well enough when it is taken as a solid. Are you just looking for something easy to swallow?Are there any forms of resveratrol that are water-soluble enough to be taken in a liquid?
#497
Posted 26 March 2007 - 09:38 AM
Since resveratrol is phenolic, it should be possible to ionize it in basic solution. (resveratol pKa = 9.14) It might be possible for the pH of such a solution to be adjusted so that you had a soluble phenoxide anion of resveratrol, but the solution was not so caustic that you couldn't consume it... but why would you want to go to the trouble? Resveratrol is absorbed well enough when it is taken as a solid. Are you just looking for something easy to swallow?
Re:swallowing. I have taken a habit a regular amount of red wine daily (<one glass), because the overall mortality lowering due cardiovascular benefits (alcohol, red wine especially) and various other things (red wine only). The problem is that even small amounts of alcohol increases the risk of cancer in organs exposed to alcohol prior to its liver metabolization (i.e. pharynx, larynx, GI tract etc.). I was wondering, whether swallowing resveratrol could protect againts this risk, since these organs are also exposed to unmetabolized resveratrol. Taking a pill would probably reduce these benefits.
#498
Posted 26 March 2007 - 05:52 PM
BTW, my entire oral cavity and GI tract are stained purple by blueberries and schizandra......
#499
Posted 26 March 2007 - 09:29 PM
Right on! I envision a whole resveratrol product line: Mouthwash, gargle, eyedrops, skin creams, shampoo, lip gloss.....
BTW, my entire oral cavity and GI tract are stained purple by blueberries and schizandra......
So resveratrol will be the new green tea?
#500
Posted 26 March 2007 - 10:50 PM
Since resveratrol is phenolic, it should be possible to ionize it in basic solution. (resveratol pKa = 9.14) It might be possible for the pH of such a solution to be adjusted so that you had a soluble phenoxide anion of resveratrol, but the solution was not so caustic that you couldn't consume it... but why would you want to go to the trouble? Resveratrol is absorbed well enough when it is taken as a solid. Are you just looking for something easy to swallow?
Well the reason I asked is not important enough to go about all that you described, most of which went over my head anyway. I thought it may be a nice option if someone wanted for example to mix 300 or 500mg of it in a batch of juice or tea to drink throught the day. If it turns out that spreading out the dosing is beneficial, even better.
#501
Posted 26 March 2007 - 11:15 PM
Since resveratrol is phenolic, it should be possible to ionize it in basic solution. (resveratol pKa = 9.14) It might be possible for the pH of such a solution to be adjusted so that you had a soluble phenoxide anion of resveratrol, but the solution was not so caustic that you couldn't consume it... but why would you want to go to the trouble? Resveratrol is absorbed well enough when it is taken as a solid. Are you just looking for something easy to swallow?
Well the reason I asked is not important enough to go about all that you described, most of which went over my head anyway. I thought it may be a nice option if someone wanted for example to mix 300 or 500mg of it in a batch of juice or tea to drink throught the day. If it turns out that spreading out the dosing is beneficial, even better.
That is what I do. It remains in suspension at least. No powder accumulates at the bottom or anything.
#502
Posted 26 March 2007 - 11:46 PM
That is what I do. It remains in suspension at least. No powder accumulates at the bottom or anything.
Even if it sits still for long? I would think that you would at least need to shake it, not that it's a problem anyway; and of course you probably couldn't rely on it being very evenly distributed either, if that's important.
Edited by niteinnyc, 27 March 2007 - 04:27 AM.
#503
Posted 27 March 2007 - 05:42 AM
#504
Posted 27 March 2007 - 08:09 AM
#505
Posted 27 March 2007 - 03:53 PM
quick anecdotal update: I have taken CL resv at 500mg for a few days now and still no "emodin effects" ... everything normal. Someone mentioned it takes a while to kick in, how long?
You may not be affected by emodin, or there may be little or no emodin in your sample. It's also possible there is little or no resveratrol in it, either. :(
It's possible Country Life are now using a low-emodin extract.
50% extracts are not uniform in particle size or density. The smaller, denser particles settle to the bottom with handling, and the "twigs and stems" rise to the top. Unless the material is carefully mixed and agitated as part of the encapsulation process, the beginning of the run may be high in emodin, the emodin content can drop throughout the run, half way through you might have high resveratrol, little or no emodin, at at the end you'll get cellulose and starches, little or no resveratrol.
This is speculative, I don't know how Country Life processes their product, but I do know extract powders will vary considerably from top to bottom in emodin content after gentle shaking and handling.
#506
Posted 27 March 2007 - 07:39 PM
#507
Posted 27 March 2007 - 08:05 PM
#508
Posted 27 March 2007 - 09:58 PM
Effects of resveratrol in inflammatory arthritis.
* Elmali N,
* Baysal O,
* Harma A,
* Esenkaya I,
* Mizrak B.
Department of Orthopaedics and Traumatology, Inonu University Medical Faculty, 44069, Malatya, Turkey, nelmali@hotmail.com.
Nuclear factor kappa B (NF-kappaB), is a pivotal transcription factor involved in the activation of the TNF-alpha and IL-1beta genes. Activation of NF-kappaB in synovial cells is a feature seen in arthritis patients. Resveratrol, a polyphenolic, natural phytoalexin found with particularly high levels in grape skin and red wine is potent and specific inhibitor of TNF-alpha and IL-1beta induced NF-kappaB activation. We aimed to determine the in vivo effects of intra-articular injections of resveratrol on cartilage and synovium in an experimental rabbit inflammatory arthritis model. MATERIALS AND METHODS: Arthritis was induced by intra-articular injection of three times of 50 mug lipopolysaccharide (LPS) at day 0, 4 and 8 at 4-day intervals into the knee joints of rabbits. To the test group, 10 muMol/kg resveratrol in the DMSO was injected in the knees at day 0 and then it was continued once daily for 2 weeks. To the control group the same time and amount of DMSO was injected the knees of rabbits. All rabbits were killed 1 week after the last injection and cartilage tissue and synovium were evaluated with semiquantitative scoring histologically. RESULTS: According to control group in the resveratrol group, significantly decreased cartilage destruction was determined by H&E staining (p = 0.04). Loss of matrix proteoglycan content in the cartilage was much lower, as determined by safranin O staining (p = 0.03). We also observed marked synovial inflammation after intra-articular injection to control knees, but not in the resveratrol treated group knees (p = 0.01). CONCLUSION: This study suggests that intra-articular injection of resveratrol may protect cartilage against the development of experimentally induced IA.
#509
Posted 28 March 2007 - 02:04 AM
Someone mentioned it takes a while to kick in, how long?
It took me over two months before the emodin kicked in but other than flatulence (not too excessive), I've had no problems. I am taking Longevinex, Natures Way, NSI and Orchid 98%. My guess it's the Natures Way and the NSI.
#510
Posted 28 March 2007 - 07:11 AM
The emodin effect kicked in fairly quickly for me (a few days, IIRC), and the severity of the effect remains variable, but hasn't entirely resolved. For me, it seems to exacerbate any GI upset I might have, varying from undetectable to quite inconvenient. [huh] I (STM resv. has enabled me to function at a higher level WRT productive, alert, wakeful hours, and to withstand physical, emotional, and psychological stressors better than I did previously. Nonetheless, my GI tract responses still inform me there's a price to be paid, at least with my current regime. Like those who have posted above, I continue to use a variety of t-resv. sources, ranging from high purtity (Orchid 99%+ purity, 98% purity PC extract), to medium (50% in CL, Bioforte). I use these because A.) I've already aquired the 50% extract caps; B.) I also have concerns regarding the true t-resv. content of various products; C.) caps are often much more convenient (e.g. work; travel); C. so little is currently understood regarding relative absorption and effectiveness of t-resv. supplements (i.e. synthetic vs. extract, with or without lipids, meals, alcohol, etc.....).
t times when I am relaxed and rested (most recently a week's vacation last month), I have no emodin symptoms, but, I have had a background tendency for IBS (or, at least, that's what it seems to be- I've not been "formally" diagnosed), and at times when I get too little sleep, eat under stressful conditions, at irregular hours (almost always lately! [sad] ),
my symptoms return.
Edited by tintinet, 28 March 2007 - 07:40 AM.
4 user(s) are reading this topic
0 members, 4 guests, 0 anonymous users