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Medical Forum / Diseases and Disorders / Arthritis / August 2007High Dose Resveratrol
A number of people I corresond with seem to have found that high dose resveratrol helps. For me it's the only thing that seems to have reversed the course of the disease, rather than just provide pain relief. The swelling in my big-toe joint is visually reduced, and I can bend the toe without pain when walking. My fingers don't hurt anymore. A doctor I asked about this emailed me: "I personally have degenerative arthritis in my right wrist which produced swelling, limitation in motion, tenderness and pain. After a few weeks(I can't remember exactly how long) on an average of 2 grams resveratrol 99%/ day, all pain and swelling is gone. I assume due to SIRT1 suppression of NF-kappaB and inflammatory cytokines. Amazing." I used a 98% extract between 500 mg and 2 grams daily; reversal of symptoms (more than just alleviating pain) did not occur below 1 gram a day, and took several weeks. Because I was adjusting the dose upward toward the two gram point, I can't untangle the dose level from the time it took to see such improvement. However, pain relief superior to that provided by Ibuprufen occurred within a few days even at lower doses. Has anyone else here tried resveratrol for their symptoms? What were the results? What dosage or brand did you use? >A number of people I corresond with seem to have found that high dose >resveratrol helps. Hi there, First of all I am going to assume that you are sincere, and will not come back in another post trying to sell us something. I have to admit that I am a little suspicious due to the fact that you seem to know/be in correspondence with several people who use resveratrol. Given that I had not heard of this product before, that sort of seemed suspicious. That suspicion aside, I did some research of this product. It seems as though this is a nutrient found in the skins of grapes, "wine, grape juice, peanuts, and berries of Vaccinum species, including blueberries, bilberries, and cranberries" (Pauling Institute, 2005). it does have some anti-inflammatory properties that have been observed in vivo, but there have not yet been any conclusive double blind studies that substantiaate this effect in humans. Part of the issue seems to be that the product is rapidly metabolized and is therefore not available for use in its purest form. The bottom line is that it looks good for the treatment of a variety of conditions but until it becomes available in a form the body can actually use, it may be no more that a money grab when sold by the non-medical community. Having said that, I see no harm in eating a diet rich in the foods that contain resveratrol. Please check the following website for more information: http://lpi.oregonstate.edu/infocenter/phytochemicals/resveratrol/ Rose @}>->-- Being educated means that rather than fearing the unknown, one seeks to understand it. RB Please remove "Ima" to reply. >>A number of people I corresond with seem to have found that high dose >>resveratrol helps. [quoted text clipped - 23 lines] > Having said that, I see no harm in eating a diet rich in the foods > that contain resveratrol. I'm with you. I love my fresh blueberries on my cereal or cottage cheese. But I find it very hard to believe that humans need or can use a lot of these "super supplements" that keep surfacing. Kind of like the commercial for the vitamin that will make sure "your man" get enough lypocene. How many guys out there aren't getting any tomato sauce products in their diets? Or couldn't with very little effort. Pizza, ketchup and spaghetti anyone? Lasagna? Jo > >A number of people I corresond with seem to have found that high dose > >resveratrol helps. [quoted text clipped - 30 lines] > > Please remove "Ima" to reply. If you go to www.imminst.org//forum/index.php?s=&act=SF&f=6 you will find a foum on supplements; several threads are devoted to high-dose resveratrol. These people are running tests on themselves at doses of 500 mg, to several times that. The substance is bio-available if enough is taken under the right conditions: with food, or with an emulsifier. Also, it is peak levels, rather than constant exposure that bring about the effects; It works by witching on certain genes, including SIRT1, which remain switched one even after the blood levels have dropped when the resveratrol is metabolized. Several effects have been reported, including lower blood pressure, weight loss, and relief of arthritic symptoms. That's how I got into using it. I'd thought people on this board might be experimenting with it to. The substance is recognized as safe by the EPA, toxicity studies have shown large doses are harmless. One thing is clear, though: the amount of resveratrol one can get from one's diet is inadequate to obtain the effects Ive noted with arthritis. Ok thank-you for the link. I see that the link is affiliated with the immortality institute. I personally have difficulty with that concept of taking products with the goal of achieving a lifespan that is longer than typical. In fact, I switched doctors because my family doctor belonged to the AAAA (American Anti-Aging Association) and because I went in with a broken arm and he tried to convince me to try DHEA and HGH. Until research can actually substantiate that these products do what they are purported to do and _do no harm_, I plan to avoid them. The bill of goods that the AAAA tries to sell is that you can live to be 150. Anyone with unrelenting chronic pain would be thankful to live a normal lifespan painfree that to extend life with no quality. Regarding your resveratrol, I would say the same thing. Show me actual controlled double blind studies and you may have a case. Lay people experimenting upon themselves is hardly scientific. Have you heard of the placebo effect? How do you control for that? How do you ensure the bioavailability of the product? I am not against anti-oxidants and a healthful diet. I am against using products, natural or not, without good evidence that they work. Rose @}>->-- Being educated means that rather than fearing the unknown, one seeks to understand it. RB Please remove "Ima" to reply. > Ok thank-you for the link. I see that the link is affiliated with the > immortality institute. I personally have difficulty with that concept [quoted text clipped - 19 lines] > > Please remove "Ima" to reply. Interesting doctor you have there. DHEA has been shown to do little, if anything , in healthy individuals, and HGH is more likely to shorten life than prolong it, judging by the studies that have been done. The evidence for resveratrol - in published studies, at any rate -- has been in animal models, but the mechanisms by which it it works is commone to all eukaryotic life forms. So much so, those familiar witht he biochemistry and genetics expect human studies to show the same effects. Such human trials are underway. You have a point about the Immortality Institute - an unfortunate name - but many of the members are biochemists, biologists, physisicists, etc with a goal of extending human life. Trying for immortality is like trying to build a perpetual motion machine, an impossibility. The argument that using artificial means to prolong life - in this case through supplements -- is inately wrong, strikes me as peculiar. Such a Luddite view would have prevented the development of modern medicine. If you won't even take an NSAID for your arthritis, what would you use? Resveratrol has been shown to be an effective COX2 inhibitor, it has been shown to suppress NF-kappaB and inflammatory cytokines in published studies, all of which would be beneficial for arthritis. I've tried using it with good results, as have others. You can wait fove or tn years for published studies and FDA approval, or get relief now. I had hoped to share this information with others, and I am surprised no one here has tried it, or even heard of it. If you won't even take an NSAID for your arthritis, what >would you use? I didn't say that I wouldn't take an NSAID. I believe strongly in modern medicine and evidence based practices. Resveratrol may very well be effective, but I need much more than anecdotal evidence throught the words of people experimenting with the product on their own. I also am not against using medications that prolong life and add to the quality of life. I would hardly classify my point of view as being "Luddite". At the time my then family doctor was advocating his anti-aging regimen I had uncontrolled RA. It seemed obscene to me that a healthy person was trying to prolong his life when there were so many sick and dying that could not even enjoy a "normal" lifespan. I couldn't rationalize him living to be 125 (which is what he was advertizing) while I had friends and neighbours who were struggling with cancer. In my opinion it is far better to cure the ill, than add years to those who already enjoy good health. Rose @}>->-- Being educated means that rather than fearing the unknown, one seeks to understand it. RB Please remove "Ima" to reply. >... In my opinion it is far better to cure the ill, than add > years to those who already enjoy good health. > Rose @}>->-- > Being educated means that rather than fearing the unknown, one seeks to understand it. RB The two are not mutually exclusive. As for resveratrol being untried, enough is known about it to know that there is a very high probability that it works, without undesired side effects. I'd hoped the information would help people. You can wait for FDA approval, or try and get relief now. There are three different companies selling it in sufficient strength over the internet; I am not associated with nor will I profit from any of them. Revgenetics, Megaresveratrol, and Bioforte by Biotivia. The only healthfood store formulation I'd recommend is Country Life. The others have to little. > If you go to www.some.org//forum/ you will find a foum on supplements; > several threads are devoted to high-dose resveratrol. These people are > running tests on themselves at doses of 500 mg, to several times that. If you go to the CDC web site, you'll find all this information and more without relying on what guinea pigs running tests on themselves have to say. ---------------------------------------------------------------------------- ---- Gene name (HAGRID: 0150) HUGO symbol SIRT1 Aliases SIR2L1 Common name sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) Potential relevance to the human ageing process Main reason for selection Entry selected based on evidence directly linking the gene product to ageing in a non-mammalian animal model Description SIRT1 is a NAD-dependent deacetylase, which has the ability to regulate a number of processes by deacetylating key proteins, such as TP53 [0734]. In yeast, the SIRT1 homologue sir2 has been linked to cellular senescence [0200]. Increasing the levels of SIRT1 homologues in fruit flies [1284] and roundworms [0199] extends lifespan. SIRT1-null mice are born smaller than controls with evidence of developmental retardation. Depending on their genetic background, SIRT1-null mice either die shortly after birth or reach adulthood, the latter being smaller than controls and sterile [0201]. SIRT1 is overexpressed in calorie restricted rats, a response attenuated by insulin (INS) and IGF1 [1328]. Increased dosage of SIRT1 in pancreatic beta cells enhanced INS secretion [1481]. Although SIRT1 could impact on age-related diseases, such as type 2 diabetes, its role on human ageing has not been established. Cytogenetic information Cytogenetic band 10q21.3 Location 69,314,432 bp to 69,348,147 bp Orientation Plus strand Display region using the UCSC Genome Browser Protein information Function DNA condensation, energy apparatus, stress response Cellular location nucleus Expression ubiquitous Gene Ontology GO:0006342; chromatin silencing; Process GO:0006350; transcription; Process GO:0006355; regulation of transcription, DNA-dependent; Process GO:0006471; protein amino acid ADP-ribosylation; Process GO:0006915; apoptosis; Process GO:0007519; striated muscle development; Process GO:0030154; cell differentiation; Process GO:0003677; DNA binding; Function GO:0003950; NAD+ ADP-ribosyltransferase activity; Function GO:0008270; zinc ion binding; Function GO:0016787; hydrolase activity; Function GO:0046872; metal ion binding; Function GO:0005634; nucleus; Cellular component GO:0005677; chromatin silencing complex; Cellular component Protein-protein interactions Interacting proteins EP300. Display interactions using the IGD Retrieve sequences for SIRT1 ORF ORF CDS CDS Homologues in model organisms P. troglodytes SIRT1 (sirtuin 1) C. familiaris LOC489012 (similar to NAD-dependent deacetylase sirtuin-1 (hSIRT1) (hSIR2) (SIR2-like protein 1)) M. musculus Sirt1 (sirtuin 1 ((silent mating type information regulation 2, homolog) 1 (S. cerevisiae)) R. norvegicus Sirt1_predicted (sirtuin 1 ((silent mating type information regulation 2, homolog) 1 (S. cerevisiae) (predicted)) G. gallus SIR2 (sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae)) D. melanogaster Sir2 (CG5216-PA) C. elegans sir-2.1 (yeast SIR related) HomoloGene (56556) Selected references [1810] Progressive loss of SIRT1 with cell cycle withdrawal, PubMed [1804] Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage, PubMed [1801] Sirtuins in aging and age-related disease, PubMed [1818] The biochemistry of sirtuins, PubMed [1776] Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer's disease amyloid neuropathology by calorie restriction, PubMed [1770] Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP-1 in response to DNA damage, PubMed [1808] Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation, PubMed [1601] MCH-/- mice are resistant to aging-associated increases in body weight and insulin resistance, PubMed [1586] SirT1 fails to affect p53-mediated biological functions, PubMed [1616] Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells, PubMed [1570] Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients, PubMed [1583] FOXO transcription factors at the interface between longevity and tumor suppression, PubMed [1806] Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival, PubMed [1564] Sir2 blocks extreme life-span extension, PubMed [1582] Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses, PubMed [1566] Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity, PubMed [1558] Neuronal protection by sirtuins in Alzheimer's disease, PubMed [1769] Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity, PubMed [1574] SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling, PubMed [1653] Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells, PubMed [1481] Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice, PubMed [1575] Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins, PubMed [1480] Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress, PubMed [1547] Calorie restriction and SIR2 genes--towards a mechanism, PubMed [1300] Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1, PubMed [0173] Nutrient availability regulates SIRT1 through a forkhead-dependent pathway, PubMed [1284] Sir2 mediates longevity in the fly through a pathway related to calorie restriction, PubMed [1578] Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration, PubMed [1285] Sirtuin activators mimic caloric restriction and delay ageing in metazoans, PubMed [1095] Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity, PubMed [1328] Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase, PubMed [1068] The sir2 family of protein deacetylases, PubMed [1138] Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma, PubMed [1805] Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase, PubMed [1071] Mammalian SIRT1 represses forkhead transcription factors, PubMed [0990] Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase, PubMed [0980] Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice, PubMed [1710] Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state, PubMed [0177] A Drosophila homologue of Sir2 modifies position-effect variegation but does not affect life span, PubMed [0201] The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis, PubMed [0202] Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction, PubMed [1425] Mutations in DNA replication genes reduce yeast life span, PubMed [0734] Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence, PubMed [0735] hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase, PubMed [1070] Negative control of p53 by Sir2alpha promotes cell survival under stress, PubMed [0199] Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans, PubMed [0200] The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms, PubMed [1493] Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae, PubMed Display PubMed References Associated with this GeneID; Search PubMed, Search Scirus, or Search Google Scholar On Aug 2, 3:09 pm, "california_chief" <Fire_Chief@Jamacha_Junction_FD.ca.us> wrote: > r...@my-deja.com wrote: > > If you go towww.some.org//forum/ you will find a foum on supplements; [quoted text clipped - 14 lines] > (S. cerevisiae) > Potential relevance to the human ageing process That provides only partial information vis-a-vis resveratrol's effects on cytokines and arthritis. Try this paper: Inflammation. 2007 Apr;30(1-2):1-6. Effects of resveratrol in inflammatory arthritis.Elmali N, Baysal O, Harma A, Esenkaya I, Mizrak B. Department of Orthopaedics and Traumatology, In?n? 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 The point being that the mechanism that protected the rabbits against induced arthritis, should address the same mechanisms in human sufferers from the condition. The medical doctor I corresponded with tried using high dose resveratrol on himself,(there is a long tradition of physicians trying new medications on themselves) and had very positive results. I tried it also with dramatic results. I wouldn't stop using it now unless forced. Others have noted positive effects as well. Here's another paper: lmali N, Esenkaya I, Harma A, Ertem K, Turkoz Y, Mizrak B. Related Articles, Links Effect of resveratrol in experimental osteoarthritis in rabbits. Inflamm Res. 2005 Apr;54(4):158-62. PMID: 15883738 By the way, these "guinea pigs" are largely bio-chemists, biologists, physicians and otherwise well educated individuals. I would hope people would do the necessary research, and decide for themselves. When I was at WalMart today to get my grape seed extract (Spring Valley which I always get), they only had it with Resveratrol so I guess I'll be testing it on me! Gwen >> If you go to www.some.org//forum/ you will find a foum on supplements; >> several threads are devoted to high-dose resveratrol. These people are [quoted text clipped - 193 lines] > Search > Scirus, or Search Google Scholar > When I was at WalMart today to get my > grape seed extract (Spring Valley which I always get), they only had it > with Resveratrol so I guess I'll be testing it on me! > Gwen Since it occurs naturally in grapes, I suspect its been in your grape seed extract all along. Or that at least the makers of grape seed extract would have plenty of it lying around. Adding it to the label is likely just marketing. Jo > <sweetpickl...@SPAMknology.net> wrote in message > [quoted text clipped - 12 lines] > > Jo That is not the case; grape seed extracts contain no measurable resveratrol; it occurs only in the skins. That is why white wine has very little resveratrol; the skins are discarded. Red wine, perhaps the richest dietary source, is fermented with the skins. Grape skin is too expensive as a source of resveratrol. Virtually all commercial resveratrol is extracted from a weed, Polygonum cuspidatum, Japanese Knotweed. I would expect the dose of resveratrol that would show strong effects in humans to be on the order of 300 or 400 mg a day, but possibly there is a synergistic effect with grape seed extract. I'd appreciate if Gwen would report if she notices any effect she can attribute to this supplement Richard |
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