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In 2003, the Life Extension Foundation® introduced a purified resveratrol supplement that was later documented to favorably alter some of the changes in gene expression that cause us to age. On January 25, 2009, CBS News 60 Minutes featured an in-depth report on the multiple benefits that resveratrol may confer in slowing and even reversing certain aspects of aging.

What differentiates Life Extension®’s resveratrol: It provides 100% standardized trans-resveratrol plus a full spectrum of natural compounds from the grape that have demonstrated remarkable biological properties. Most products currently on the market contain varying quantities of trans- and cis-resveratrol, and fail to provide enough trans-resveratrol for optimal results. In addition, Life Extension has added pterostilbene, which researchers have found works in a synergistic fashion with resveratrol to activate one’s “longevity genes.”

Research funded by Life Extension has shown that a combination of low-dose (20 milligrams) resveratrol plus grapeseed extract induced many of the favorable gene expression changes seen in calorie-restricted animals. Other studies, however, have indicated that higher doses may be needed to obtain all of resveratrol’s positive benefits including:

• Improved insulin sensitivity
• Enhanced mitochondrial function
• Reduced expression of inflammatory factors
• Protection against the toxic effects of a high-fat diet

Life Extension has meticulously evaluated published studies on resveratrol and pterostilbene to establish doses people might need to take to duplicate these remarkable laboratory findings. The results of Life Extension’s analysis yield a wide range of potentially effective doses of resveratrol and pterostilbene.

Optimized Resveratrol with Pterostilbene provides the highest dosage of trans-resveratrol of all of Life Extension's resveratrol products, as well as a broad array of grape polyphenols, quercetin and pterostilbene. The pterostilbene content of this formula (500 micrograms) is equivalent to over 20 cups of blueberries.

Contains corn.
This product contains NO milk, egg, fish, peanuts, crustacean shellfish (lobster, crab, shrimp), soybeans, tree nuts, wheat, yeast, gluten, or rice. Contains NO sugar, and no artificial sweeteners, flavors, colors, or preservatives.

† Same material as research trials.
Pterospan™ (Pure Pterostilbene) and SMART™ are trademarks of Pharma Science Nutrients, Inc., and are used here under license. All rights reserved worldwide.

Dosage and Use

• Take one capsule daily with or without food, or as recommended by a healthcare practitioner.

Caution

If you are taking anti-coagulant or anti-platelet medications, or have a bleeding disorder, consult your healthcare provider before taking this product.

Background

It was not until a scientist tried to figure out why the French can eat so much fat and not get heart disease. It turns out that part of the answer to the “French paradox” is resveratrol found in red wine. Resveratrol is naturally created by certain vines, pine trees, peanuts, grapes, and other plants. One of these plants (Polygonnum cuspidatum) is an ingredient in traditional Asian medicines that are prescribed for liver and heart conditions. Resveratrol is classified as a polyphenol because of its chemical structure. Polyphenols make up a huge group of plant compounds that are further broken down into other classifications such as flavonoids, proanthocyanidins, and the like.

Heart/Blood Vessels and Resveratrol
When researchers deconstruct heart disease, they see many different things happening at the level of the cell. Cholesterol and other fat-related substances are one small part of a bigger picture that involves many other factors. Fortunately, many facets of heart disease can be controlled through dietary means. Resveratrol is a dietary agent that has powerful and diverse effects on the heart and blood vessels.*

The “French paradox” says that a person can eat a lot of fat, yet not get heart disease. Why? One of the reasons is that the wine they drink contains resveratrol, which is a powerful antioxidant. By now, many people have heard that oxidized low-density lipoprotein (LDL) is a problem in heart disease. This is why vitamin E helps prevent heart problems—it scavenges the radicals that oxidize this fat/protein. However, the kind of radicals that vitamin E blocks are not the only kind of free radicals people have to worry about. There are other types. In a study published in Free Radical Research,¹ resveratrol was put to the test against vitamin E and a synthetic antioxidant. All three were very good at scavenging artery-damaging radicals, but resveratrol emerged as the best defense against certain types of radicals. This points out the importance of using a multi-approach to antioxidants.*

One of the serious complications of free radical damage is hardening and thickening of arteries. A “vicious cycle” of radicals, artery damage, and narrowing due to scar tissue that, in turn, promotes more free radical activity and more damage, has been described.² Resveratrol, melatonin and Probucol are suggested as treatments for this progressive process. Resveratrol’s antioxidant action helps stop free radical damage and opens the arteries by enhancing nitric oxide.*

Nitric oxide is a critical component of heart/artery function. It allows blood vessels to “relax,” which enhances blood flow. In a recent study, a high-cholesterol diet decreased nitric oxide by about a third. Resveratrol supplements significantly reversed the trend.³ In this respect, resveratrol is similar to Viagra, which also affects nitric oxide. However, whereas Viagra only affects small vessels, resveratrol affects the main arteries.*

Resveratrol also stops the proliferation of cells in blood vessels that narrow the arteries,⁴ and it also keeps blood cells from sticking together.⁵ Both are very important for preventing heart attacks. The ability of resveratrol to keep blood cells from sticking together was investigated by Canadian researchers who wanted to know what role, if any, other components of wine might play in the process. They found that ethanol itself inhibited one type of stickiness-promoter (thrombin), and quercetin (another polyphenol) inhibited a different one (12-HETE), but nothing else they tested was active against this aspect of heart disease except resveratrol, which inhibited not only thrombin, but a host of other stickiness-promoting factors.⁶*

Spinal Cord Injury, Stroke and Resveratrol

A recent study from China showed that resveratrol reversed the signs of inflammatory response to spinal cord injury on a level comparable to prednisone (a steroid used to reduce inflammation), but with better energy compensation and protection against free radicals, when injected immediately after injury. Results could be very important for people who undergo serious brain/spinal trauma or stroke. In these types of injuries, the body’s response causes further injury, and for that reason, people are treated with drugs like cortisone, and in the case of stroke—aspirin. The idea is to reduce the body’s inflammatory response to the injury. Besides helping to ameliorate this type of injury through free radical blockade, resveratrol actually inhibits specific enzymes that change the way individual cells respond to the injury. It’s possible that if a person regularly takes supplemental resveratrol, they will be more likely to withstand a stroke or other injury to the brain. This has been demonstrated in rodents pretreated 21 days with resveratrol.⁷ Less motor damage, and less brain damage occurred post-stroke.*

Cancer and Resveratrol
Cancer is, perhaps, the most dynamic area of resveratrol research. Resveratrol is the first natural medicinal to have solid evidence behind it showing that it blocks or stops many stages of cancer. Resveratrol not only prevents cancer, it’s being proposed as an additional treatment.^8-10*

The number of studies has exploded in the past three years, with the depth of knowledge about this polyphenol increasing with each report. Resveratrol is a broad-spectrum agent that stops cancer in many diverse ways, from blocking estrogen and androgens to modulating genes.^11-14*

Some of the latest information about it shows that resveratrol causes a unique type of cell death,⁸ and kills cancer cells whether they do or do not have the tumor suppressor gene, p53.¹⁵ It also works whether cancer cells are estrogen receptor-positive or negative.^12,16*

In addition to these findings, researchers are beginning to uncover the ability of resveratrol to augment other chemotherapies. For example, vitamin D3 converts to a steroid that inhibits the growth of breast cancer cells. Researchers at the University of Notre Dame have shown that resveratrol increases the effects of vitamin D.¹⁷ Other research shows that it causes drug-resistant non-Hodgkin’s lymphoma cancer cells to become susceptible to chemotherapeutic drugs (Gemcetabine, Navelbine, cisplatinum, Paclitaxel, and TRIAL).⁸*

How Much Resveratrol Is In Wine?
In order to understand how much resveratrol is in wine, one must realize that resveratrol is a natural substance made by grapes and other plants in response to fungal infection. How much resveratrol is in a glass of wine depends, first, on whether the grapes were grown organically, and, second, how the wine was made. Grapes sprayed with pesticides that prevent fungal infection contain little, if any, resveratrol. Wines grown in dry climates have less resveratrol than those grown in humid areas. Red wines contain more than white because of how red wine is made. The end result of all of this is that organic red wines from certain areas of Europe contain the highest level of resveratrol. But most wines contain either no resveratrol at all, or very little (less than a milligram per glass).

The only sure way to obtain a certain amount of resveratrol daily is to take a standardized extract. Standardization ensures a consistent amount of resveratrol with consistent high quality. The finest resveratrol available comes from Europe. It is made from organic French grapes known for their high resveratrol content. The resveratrol is carefully extracted to retain other compounds (polyphenols) that naturally occur with it. This pharmaceutical wine extract is then enhanced with resveratrol extracted from the roots of a medicinal plant (Polygonnum cuspidatum) used for centuries in Asia for the treatment of inflammation, heart, blood vessel and liver disease, skin and lipid problems. The result is a product that retains the active parts of wine in a natural balance with increased potency and consistent quality.

References

1. Tadolini, B. et al. Resveratrol inhibition of lipid peroxidation. Free Radic. Res. 2000;33:105-14.

2. Simonini, G. et al. Emerging potentials for an antioxidant therapy as a new approach to the treatment of systemic sclerosis. Toxicology 2000;155:1-15.

3. Zou JG, et al. Effect of red wine and wine polyphenol resveratrol on endothelial function in hypercholesterolemic rabbits. Int. J. Mol. Med. 2003;11:317-20.

4. Haider, U.G. et al. Resveratrol increases serine 15-phosphorylated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells. Mol. Pharmacol. 200;363:925-32.

5. Zbikowska, H.M. et al. Antioxidants with carcinostatic activity (resveratrol, vitamin E and selenium) in modulation of blood platelet adhesion. J. Physiol. Pharmacol. 2000;51:513-20.

6. Pace-Asciak, C.R. et al. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin. Chim. Acta. 1995;235:207-19.

7. Sinha, K. et al. Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats. Life Sci. 2002;71:655-65.

8. Cal, C. et al. Resveratrol and cancer: chemoprevention, apoptosis, and chemoimmunosensitizing activities. Curr. Med. Chem-Anti-Cancer Agents 2003;3:77-93.

9. Pervaiz, S. Resveratrol–from the bottle to the bedside? Leuk. Lymphoma 2001;40:491-8.

10. Ding, X.Z. et al. Resveratrol inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Pancreas 2002;25:e71-e76.

11. Gusman, J. et al. A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol. Carcinogenesis 2001;22:1111-17.

12. Lu, R. et al. Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells. J. Cell. Physiol. 1999;179:297-304.

13. Serrero, G. et al. Effect of resveratrol on the expression of autocrine growth modulators in human breast cancer cells. Antioxid. Redox. Signal 2001;3:969-79.

14. Mitchell, S.H. et al. Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Cancer Res. 1999;59:5892-5.

15. Narayanan, B.A. et al. Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002;70:1821-39.

16. Pozo-Guisado, E. et al. The antiproliferative activity of resveratrol results in apoptosis in MCF-7 but not in MDA-MB-231 human breast cancer cells: cell-specific alteration of the cell cycle. Biochem. Pharmacol. 2002;64:1375-86.

17. Wietzke, J.A. et al. Phytoestrogen regulation of a vitamin D3 receptor promoter and 1.25-dihydroxyvitamin D3 actions in human breast cancer cells. J. Steroid Biochem. Mol. Biol. 2003; 84:149-57

Printed with permission of Life Extension www.lef.org

Warning: These products are not intended to diagnose, treat, cure or prevent any disease. Please consult with a healthcare professional before starting any diet or exercise program. Some of these products are not recommended for individuals under the age of 18.