Journal Reports Resveratrol Doubles Endurance
11-16-2006 01:07 PM
Journal Reports Resveratrol Doubles Endurance
New York Times
November 16, 2006
Journal Reports Drug That Doubles Endurance
By NICHOLAS WADE
Given that some athletes will take almost anything to gain a one percent edge in performance, what might they do for a 100 percent improvement? That temptation is made somewhat more real by a report today in a leading journal about a drug that doubles the physical endurance of mice running on treadmills. And it could only be more tempting, because the drug in question has also been reported to extend the lifespan of mice.
An ordinary lab mouse will run about one kilometer — five-eights of a mile — on a treadmill before collapsing from exhaustion. But mice given resveratrol, a minor component of red wine and other foods, run twice as far.
They also have a reduced heart rate and energy-charged muscles, just as trained athletes do, according to an article published online in Cell by Johan Auwerx and his colleagues at the Institute of Genetics and Molecular and Cellular Biology in Illkirch, France.
“Resveratrol makes you look like a trained athlete without the training,” Dr. Auwerx (pronounced OH-wer-ix”) said in an interview.
He and his colleagues said the same mechanism seems likely to operate in humans, based on their analysis, in a group of Finnish subjects, of the gene that is influenced by the drug.
Their rationale for testing resveratrol was evidence obtained three years ago that it could activate a genetic mechanism known to protect mice against the degenerative diseases of aging and to prolong their lifespan by 30 percent.
Dr. Auwerx, whose interest is in the genetic control of metabolism, decided to see if resveratrol would offset the effects of a high-fat diet, specifically the metabolic disturbances that are the precursors of diabetes and obesity, known as metabolic syndrome.
In his report, he and his colleagues say that very large doses of resveratrol protected mice from gaining weight and from developing metabolic syndrome.
Dr. Auwerx attributes this change in large part to the significantly increased number of mitochondria he detected in the muscle cells of treated mice.
Mitochondria are the organelles within the body’s cells that generate energy. With increased mitochondria, the treated mice were able to burn off more fat and thus avoid weight gain and decreased sensitivity to insulin, Dr. Auwerx said. He found that their muscle fibers had been remodeled by the drug into the type more prevalent in trained human athletes.
Dr. Ronald M. Evans, a leading expert on the hormonal control of metabolism at the Salk Institute, said that the report by Dr. Auwerx’s team had “shown very convincingly that resveratrol improves mitochondrial function” and fends off metabolic disease.
Dr. Evans described the study as “very important, because it is rare that we identify orally active molecules, especially natural molecules, that have such a broad-based, positive effect on a problem as widespread in society as metabolic disease.”
Dr. Ronald Kahn, director of the Joslin Diabetes Center in Boston, said the research would focus attention on the sirtuins, a recently discovered group of enzymes that resveratrol is believed to affect. Noting that he is a scientific advisor to Sirtris, a company developing drugs that activate the sirtuins, Dr. Kahn said, “Certainly, drugs that act on this class of proteins have the potential to have major effects on human disease.”
Dr. Auwerx’s study complements one published earlier this month by Dr. David Sinclair of the Harvard Medical School, who found that much more moderate doses of resveratrol protected mice from the metabolic effects of a high-calorie diet. Though his mice did not lose weight, they lived far longer than undosed mice that were fed the same high-calorie diet.
The two studies were started and performed independently, Dr. Auwerx said, though he obtained supplies of resveratrol from Sirtris, which was co-founded by Dr. Sinclair, and he has become a scientific advisor to the company.
11-16-2006 01:13 PM
Oh no another not so short, short cut. And now we re proud to announce "life" the magic pill, be rich, hung, and never get out of bed.
11-16-2006 01:29 PM
Res is quickly gaining attention in biomedical circles. A phD'd researcher freind of mine says that the latest info coming out on it is completely amazing. She said that the minimum dose to achieve the "super" benefits is around 500 mg which is hard to find in the supp world as there are very few suppliers of pure res.
I know that grape seed extract stacked with ActiChrome really enhanced my cardio output. Since Res is a constituent of GSE, it makes sense to me.
11-16-2006 05:56 PM
ive been reading some interesting tidbits on it myself lately,becoming quite interested.
i looked it up at puritans pride and here is what i found
RESVERATROL/GRAPE EXTRACT 60 mg. Capsules
• A Natural Source of Resveratrol
Our Grape Extract contains natural extracts of both the skin and seeds of the grape. This product contains flavonoid polyphenols and resveratrol, the beneficial substance found in red wine.** Grape Extract has been shown to help support heart health.** Supplementing with Grape Extract promotes antioxidant support by helping to fight cell-damaging free radicals**. Cell-damaging free radicals can come from anywhere - auto exhaust, smoking, even your own body and can lead to premature aging of cells.** Adults can take two capsules two times daily.
but bioman your saying the ideal effects cmoe from 500mg daily?dang these caps are only 60mg each,and even then it seems that its not even 60mg of res but 60mg of the gpare extract?
perhaps it would be best to source out a bulk powder thru a sponsor and cap it?id really like to see more discussion on this as it seems pretty huge
11-16-2006 06:37 PM
The Resveratrol Story
Melissa Q.B. McElderry, M.S., R.D.
Resveratrol (trans-3,5,4'-trihydroxystilbene), a compound found largely in the skins of red grapes, is a component of Ko-jo-kon, an oriental medicine used to treat diseases of the blood vessels, heart [1,2], and liver . It came to scientific attention only four years ago, however, as a possible explanation for the "French Paradox" -- the low incidence of heart disease among the French people, who eat a relatively high-fat diet . Today, it is touted by manufacturers and being examined by scientific researchers as an antioxidant , an anti-cancer agent, and a phytoestrogen . It is also being advertised on the Internet as "The French Paradox in a bottle." [A] Arkopharma, of Wallingford, Connecticut, even markets a red-wine extract antioxidant product called "French Parad'ox." This article reviews the recent research on resveratrol's physiologic activity.
While present in other plants, such as eucalyptus, spruce, and lily, and in other foods such as mulberries and peanuts, resveratrol's most abundant natural sources are Vitis vinifera, labrusca, and muscadine grapes, which are used to make wines. It occurs in the vines, roots, seeds, and stalks, but its highest concentration is in the skin , which contains 50-100 micrograms (µg) per gram . Resveratrol is a phytoalexin, a class of antibiotic compounds produced as a part of a plant's defense system against disease . For example, in response to an invading fungus, resveratrol is synthesized from p-coumaroyl CoA and malonyl CoA . Since fungal infections are more common in cooler climates, grapes grown in cooler climates have a higher concentration .
The resveratrol content of wine is related to the length of time the grape skins are present during the fermentation process. Thus the concentration is significantly higher in red wine than in white wine, because the skins are removed earlier during white-wine production, lessening the amount that is extracted . Grape juice, which is not a fermented beverage, is not a significant source of resveratrol. A fluid ounce of red wine averages 160 µg of resveratrol, compared to peanuts, which average 73 µg per ounce . Since wine is the most notable dietary source, it is the object of much speculation and research.
Many studies suggest that consuming alcohol (especially red wine) may reduce the incidence of coronary heart disease (CHD). Several studies have demonstrated that resveratrol is an effective antioxidant [7-10]. It inhibits lipid peroxidation of low-density lipoprotein (LDL) [7,8], prevents the cytotoxicity of oxidized LDL , and protects cells against lipid peroxidation . It is thought that because it contains highly hydrophilic and lipophilic properties, it can provide more effective protection than other well-known antioxidants, such as vitamins C and E . On the other hand, it is less effective than the antioxidants quercetin and epicatechin found in red wine . Reduced platelet aggregation has also been demonstrated in studies on resveratrol, further contributing to its prevention of atherosclerosis [2,9]. To date, most of the research on resveratrol's antioxidant and anti-platelet properties has been done in vitro (in an artificial environment using test-tube or tissue-culture preparations). Further studies in animals and humans are necessary to determine whether resveratrol supplementation makes sense.
Resveratrol is being studied to see how it affects the initiation, promotion, and progression of cancer. With regard to tumor initiation, it has been shown to act as an antioxidant by inhibiting free radical formation, and as an anti-mutagen in rat models . Resveratrol appears to decrease tumor promotion activity by inhibiting cyclooxygenase-1 (COX-1) [4,11,12], an enzyme that converts arachidonic acid to pro-inflammatory substances that stimulate tumor-cell growth . Studies related to progression have found that resveratrol induced human promyelocytic leukemia cell differentiation  and inhibited ribonucleotide reductase, an enzyme needed for DNA synthesis in proliferating cells . One appealing characteristic of resveratrol's anti-cancer potential is its minimal toxicity to blood-forming cells . More studies using both cellular and animal models are needed before any such data would be applicable to human use.
The similarity in structure between resveratrol and diethylstilbestrol (a synthetic estrogen) has prompted investigations into resveratrol's potential as a phytoestrogen (a plant compound that produces estrogen-like effects). However, these properties also stimulate the growth of human breast cancer cells . This finding seems contrary to its other anticancer activities, and is a cause for concern.
The Bottom Line
Laboratory tests have clearly demonstrated that resveratrol may help prevent cardiovascular disease and cancer. However, there are several reasons why recommending a population-wide increase would be premature.
* First, little is known about the absorption and clearance of resveratrol, the identities of its metabolic products, or its effects on the liver . A study in rats showed that resveratrol is absorbed in the gut and has a high affinity for the heart and liver [13,14].
* Second, the research on resveratrol has focused on its short-term effects  and has been dominated by in vitro studies on non-human models.
* Third, its role as a potentiator of breast carcinomas may significantly limit its use, even for its "proven" benefits.
* Finally, its main dietary source is red wine. Not only is its concentration in wine extremely variable, but recommending increased consumption of red wine to boost resveratrol intake could certainly do more harm than good. In spite of any beneficial aspects, red wine and other alcoholic beverages pose health risks that include liver damage and physical addiction.
The health-food industry is claiming that resveratrol is the wine component responsible for the "French Paradox." While taking resveratrol pills is certainly safer than heavy consumption of red wine, supplementing with unproven substances is generally unwise. At this point, occasional use of red wine seems far more prudent.
1. Celotti E and others. Resveratrol content of some wines obtained from dried Valpolicella grapes: Recioto and Amarone. Journal of Chromatography A 730(1-2): 47-52, 1996.
2. Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: A molecule whose time has come? And gone? Clinical Biochemistry 30:91-113, 1997.
3. Kopp P. Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the 'French paradox'? European Journal of Endocrinology 138:619-620, 1998.
4. Jang M and others. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218-220, 1997.
5. Gehm H and others. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proceedings of the National Academy of Sciences U.S.A. 94:557-562, 1997.
6. Sanders TH, McMichael RW. Occurrence of resveratrol in edible peanuts. Presentation, American Oil Chemists Society, Las Vegas, Nevada, 1998. Discussed in Peanuts contain significant amount of plant compound that may prevent risk of heart disease and cancer, a news release from The Peanut Institute, Sept 8, 1998.
7. Chanvitayapongs S, Draczynska-Lusiak B, Sun AY. Amelioration of oxidative stress by antioxidants and resveratrol in PC12 cells. Neuroreport 8:1499-1502, 1997.
8. Belguendouz L, Fremont L, Gozzelino MT. Interaction of transresveratrol with plasma lipoproteins. Biochemical Pharmacology 55:811-816, 1998.
9. Rotondo S and others. Effect of trans-resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function. British Journal of Pharmacology 123:1691-1699, 1998.
10. Frankel EN, Waterhouse AL, Kinsella JE. Inhibition of human LDL oxidation by resveratrol. Lancet 341:1103-1104, 1993.
11. Clement MV and others. Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells. Blood 92:996-1002, 1998.
12. Fontecave M and others. Resveratrol, a remarkable inhibitor of ribonucleotide reductase. FEBS Letters 421:277-279, 1998.
13. Bertelli AA and others. Evaluation of kinetic parameters of natural phytoalexin in resveratrol orally administered in wine to rats. Drugs under Experimental and Clinical Research 24:51-55, 1998.
14. Bertelli A and others. Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs under Experimental and Clinical Research 24:133-138, 1998.
11-16-2006 09:04 PM
Respected Cardiologist Breaks Ranks with Medical Establishment; Adults Must Start Taking Red Wine Extract Supplements Daily Now
BOCA RATON, Fla., Nov 10, 2006 /PRNewswire via COMTEX/ -- Dr. William Gruss -- a well respected Internist and Cardiologist who specializes in preventive cardiac care for patients who suffer from chronic heart problems, high cholesterol, high blood pressure, and diabetes -- is recommending that adults should begin taking supplements with red wine extract immediately as a way to protect their organs from the ravages of the typical, high-fat diet currently consumed by most Americans.
"Physicians shouldn't wait for the FDA to approve red wine extract. They need to tell their patients, especially obese ones, to start taking supplements with the highest levels of resveratrol they can find," says Dr. Gruss.
A recent study done by the Harvard Medical School and the National Institute of Aging is just another in a long line of studies that show heavy doses of red wine extract can lower the rate of fat-related diseases, including diabetes and liver problems, in obese mice and even extended their life expectancy. Still, the doctors conducting the research stopped short of recommending red wine extract for humans.
"This whole situation reminds me of the initial debate on fish oil. Study after study would come out touting its effects, much like what's happening with red wine extract now, and still doctors wouldn't recommend fish oil to their patients. Of course, now physicians can write a prescription for fish oil and most health insurance drug plans will pay for it," explains Dr. Gruss.
Dr. Gruss is board certified in Internal Medicine and has been in private practice in Boca Raton, Florida since 1986. A graduate of the University of Maryland Medical School, Dr. Gruss did his residency and Fellowship in Cardiology at the prestigious Mt. Sinai Medical Center in Miami.
Dr. Gruss says there are many red wine extract supplements available to consumers on the market already, and that care should be taken when deciding which one to buy.
"I recommend taking a supplement that has the highest level of resveratrol that you can find. The ideal supplement would pair the resveratrol with other 'booster' anti-oxidants to give you the maximum benefits, without having to consume enormous amounts of red wine and its alcoholic and caloric side- effects. Red wine extract is an important supplement to take," says Dr. Gruss.
11-16-2006 09:48 PM
Biotest the supplement hype-machine has a Resveratrol supplement. Not sure on the effectiveness. Though I think Biotest markets it as an anti-estrogen and testosterone enhancer. Which is odd considering it is being discussed as a possible phytoestrogen.
11-16-2006 10:53 PM
Too bad Resveratrol won't survive the digestive tract in humans so supplementation is likely pointless at this point.
11-17-2006 09:46 AM
Running with the Big Boys
Wow, just when the French wine-grape market was becoming less profitable due to world wide emergence of bio-enhanced generic wines...This was sure a lucky break for those corporations who own the vineyards!
11-17-2006 10:19 AM
Isn't this in DS's Vigor too? Remember that from somewhere.
11-17-2006 11:46 AM
Even though this is a sales pitch for a supplement, it's got some good info on rsveratrol none the less:
11-17-2006 10:04 PM
The study used oral supplementation.
Originally Posted by ersatz
Substance in red wine found to combat obesity, diabetes
11-17-2006 10:14 PM
This stuff definitely looks promising.
11-17-2006 11:12 PM
Lipid Research Laboratory and Department of Anatomy and Cell Biology, Technion Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel
2To whom correspondence should be addressed. E-mail: Fuhrman@tx.technion.ac.il.
The beneficial health effects of red wine have been attributed to the antioxidant activity of its polyphenols. The present study investigated the effects of a standardized freeze-dried powder made from fresh grapes, rich in grape-specific polyphenols and free of alcohol, on oxidative stress, atherogenicity of macrophages, and the development of atherosclerotic lesions in apolipoprotein E deficient (E0) mice. Thirty E0 mice were assigned to 3 groups. Mice consumed water alone (control), 150 µg total polyphenols/d in the form of grape powder (grape powder), or the equivalent amount of glucose and fructose (placebo) in drinking water for 10 wk. Consumption of grape powder reduced the atherosclerotic lesion area by 41% (P < 0.0002) compared to the control or placebo mice. The antiatherosclerotic effect was at least partly due to a significant 8% reduction in serum oxidative stress, an up to 22% increase in serum antioxidant capacity, a significant 33% reduction in macrophage uptake of oxidized LDL, and a 25% decrease in macrophage-mediated oxidation of LDL relative to controls. Grape powder directly protected both plasma LDL and macrophages from oxidative stress in vitro. We conclude that polyphenols from fresh grape powder directly affect macrophage atherogenicity by reducing macrophage-mediated oxidation of LDL and cellular uptake of oxidized LDL. Both of these processes can eventually reduce macrophage cholesterol accumulation and foam cell formation and hence attenuate atherosclerosis development.
11-17-2006 11:29 PM
South of the Preclinical Science Building. Large stands can be seen from the platform outside of Basic Science Building and the Dahlgren Medical Library.
Japanese knotweed is a large, bushy plant, about four to ten feet high, with leaves that are broad, with shortpoints at the tip. The greenish-white flowers grow in branching spikes. Flowers usually grow from leaf axils, and can be seen from summer to fall (Newcomb 1977).
Japanese knotweed was introduced into the New World from Eurasia (Kiple 2000).
The immature stems of Japanese knotweed are used in salads or as a cooked green (Kiple 2000). Older stalks, peeled, can be used like rhubarb. (Elias 1982)
Current Medicinal Uses
The dried root and stem of Polygonum cuspidatum, also called Hu chang, are used in traditional Chinese medicine to treat high cholesterol and other conditions (Huang 1999). It is also used as a laxative (Lewis 1977).
Polygonum root contains resveratrol (Kimura 2001), the same beneficial phytochemical found in red wine. An aqueous extract of Polygonum cuspidatum showed anti-angiogenesis activity in vitro (Wang 2004).
Contact with Japanese knotweed can cause a light-dependent rash in some people (Elias 1982).
Elias TS, Dykeman PA. Field Guide to North American Edible Wild Plants. Outdoor Life Books, New York, 1982.
Huang KC. The pharmacology of Chinese herbs, 2nd ed. CRC Press, Boca Raton, 1999: 126.
Wang S, Zheng Z, Weng Y, Yu Y, Zhang D, Fan W, Dai R, Hu Z. Angiogenesis and anti-angiogenesis activity of Chinese medicinal herbal extracts. Life Sci. 2004 Apr 2;74(20):2467-78.
Kimura Y, Okuda H. Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice. J Nutr. 2001 Jun;131(6):1844-9.
Kiple KF, Ornelas KC, ed. The Cambridge World History of Food. Cambridge University Press, Cambridge, 2000. (p. 1797)
Lewis WH, Elvin-Lewis MPF. Medical Botany: Plants Affecting Man’s Health. John Wiley & Sons, Inc., New York, 1977. (p. 284)
Newcomb L. Newcomb’s Wildflower Guide. Little, Brown and Company, Boston, 1977. (p. 190)
11-18-2006 02:46 PM
TNF-alpha-induced activation of coronary arterial endothelial cells is attenuated by resveratrol
Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells.
According to a study from the United States, "Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. However, the mechanisms by which resveratrol exerts its cardioprotective effects are not completely understood."
"Because TNF-alpha-induced endothelial activation and vascular inflammation play a critical role in vascular aging and atherogenesis, we evaluated whether resveratrol inhibits TNF-alpha-induced signal transduction in human coronary arterial endothelial cells (HCAECs)," wrote New York Medical College researchers A. Csiszar and colleagues.
"We found that TNF-alpha significantly increased adhesiveness of the monocytic THP-1 cells to HCAECs, an effect that could be inhibited by pretreatment with resveratrol and the NF-kappaB inhibitor pyrrolidine dithiocarbamate," they reported. "Previously, we found that TNF-alpha activates NAD(P)H oxidases, and our recent data showed that TNF-alpha-induced endothelial activation was prevented by the NAD(P)H oxidase inhibitor apocynin or catalase plus SOD."
"Resveratrol also inhibited H2O2-induced monocyte adhesiveness," the investigators continued. "Using a reporter gene assay, we found that, in HCAECs, TNF-alpha significantly increased NF-kappaB activity, which could be inhibited by resveratrol (>50% inhibition at 10-6 mol/l) and pyrrolidine dithiocarbamate. Resveratrol also inhibited TNF-alpha-induced, NF-kappaB-driven luciferase expression in rat aortas electroporated with the reporter gene construct."
"In TNF-alpha-treated HCAECs, resveratrol (in the submicromolar range) significantly attenuated expression of NF-kappa B-dependent inflammatory markers inducible nitric oxide synthase, IL-6, bone morphogenetic protein-2, ICAM-1, and VCAM," they noted.
"Thus resveratrol at nutritionally relevant concentrations inhibits TNF-alpha-induced NF-kappaB activation and inflammatory gene expression and attenuates monocyte adhesiveness to HCAECs," the researchers concluded. "We propose that these anti-inflammatory actions of resveratrol are responsible, at least in part, for its cardioprotective effects."
Csiszar and colleagues published their study in the American Journal of Physiology - Heart and Circulatory Physiology (Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kB inhibition. Am J Physiol Heart Circ Physiol, 2006;291(4):H1694-H1699).
For more information, contact A. Csiszar, New York Medical College, Dept. of Physiology, Valhalla, NY 10595, USA.
Publisher contact information for the American Journal of Physiology - Heart and Circulatory Physiology is: American Physiological Society, 9650 Rockville Pike, Bethesda, MD 20814, USA.
11-18-2006 02:54 PM
I wonder if the Grape Seed Extract from NOW foods is a good place to start right now? Or is this different?
11-18-2006 02:59 PM
Originally Posted by Jayhawkk
GSE has resveratrol in it.......but these studies are based on high doses of resveratrol. There are a few brands out there.
11-18-2006 03:01 PM
Hmm, I wonder what the amount of res is in it.
11-18-2006 05:08 PM
I was wondering the same thing. Wrote them asking if they knew, haven't heard back yet.
Originally Posted by Jayhawkk
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