Resveratrol is reported by the media with excited anticipation of its potential in the metabolic support of the immune system, anti-aging, sports performance, cancer concerns, and life extension. Resveratrol, found in red grapes, fruits, berries and root extracts, was first isolated in 1940 as a constituent of Japanese Knotweed and the Hy Zhang Root Extract (Polygonum capsidatum). Modernly, it has since been found in red wine and peanuts. The bio-active chemical configuration is 3,4’,5-tri-hydroxy-trans-stilbene, a potent antioxidant.

Featured on the Barbara Walters special “Live to 150,” Resveratrol has been in the news a great deal! Led by Dr. David Sinclair at Harvard University, research studies continue to find more interesting benefits from this compound, including potential anti-cancer, anti-aging, and life extension activity. Considerable attention is focused on anticancer properties, both in solid tumors and hematologic malignancies. It is not surprising that Resveratrol is shaping up to be the greatest nutritional discovery of our lifetimes. The media has nick-named Resveratrol as the “fountain of youth”, and you will soon read some of the scientific data that gave birth to this world-wide interest.

Beginning November 1, 2006 nearly 500 newspapers reported on the resveratrol story and virtually every major TV news department followed. The news media heralded a study which showed that a high-dose, “red wine molecule”, maintained the quality of life of laboratory mice (balance and coordination) as they aged despite a high-fat diet the high-fat fed mice lived 31% longer when given resveratrol.

Next, the anti-nutritional supplement news media began swaying consumers towards wine (a major source of resveratrol) because, as some authorities claimed, there was an uncertainty over the sources and safety of resveratrol supplementation. Forget that the EPA deems resveratrol to be non-toxic. Forget that animal studies show the equivalent of 21,000 milligrams in humans would be non-toxic. Forget that three human clinical trials using 500 milligrams of resveratrol have passed the safety arm of their study. Forget that the National Institute of Environmental Health Sciences has conducted a toxicity review of resveratrol, and no major side effects are noted. For the record, resveratrol is far safer than any alcoholic beverage and even safer than aspirin. When an alternative to an alcoholic beverage was available, a fact which should have been heralded, modern medicine and the news media, in a phobic aversion to dietary supplements, advised the public to “get drunk” on wine.

So 90 percent of the news reports said, until proven otherwise, wine was safer than pills. Conversely, reporters further explained it would take too much wine to produce the same health benefits as shown in the recent study and consumers would have to drink about a case of wine per day to achieve the health benefits. Reporters drove this story into the ground until one wondered why they were even reporting it.

What dosage?

The human equivalent dose for 160-pound adult would be about 1575 milligrams of Resveratrol to produce the health benefits noted in the mouse study. The reporters didn’t interpret the study carefully, published in the research journal Nature, which concluded an effective dose of 364 milligrams (for a 160-pound adult) translated to similar health benefits.

Furthermore, the mice were engorged with fat, 60% of their daily calorie intake. Americans once consumed about 45% of daily calories from fat (1965), but that number has dropped to about 34% (2002). Unfortunately, approximately 200 million Americans are reported to have a Body Mass Index greater than 26, indicating an overweight or obese status. Comprehensive review of the published literature on Resveratrol suggests a lower amount of resveratrol, 180 mg daily, would likely be effective for supporting healthy wellness.

To add to the confusion, a Big Pharma-paid university researcher “consultant” advised a Canadian news reporter that resveratrol is not biologically available in oral doses. This conflicted with published research from the Heart Institute, Montreal Canada and the recent National Institute of Health /Harvard study on aging and life extension that had proven otherwise (the laboratory study mice consumed oral doses in the research project).

Can the public sort through the spin?

One wonders how a great discovery like penicillin would be dealt with by reporters and doctors today? Recall that penicillin never underwent a double-blind, placebo-controlled study to prove its safety and effectiveness. It was first used successfully to cure an eye infection in a young boy.

Modernly, the National Institute of Health would claim penicillin was limited to evidence-based research and still unproven, subject to clinical trials and safety studies before it could be commonly prescribed. Drug companies would drive the price of penicillin to thousands of dollars, declaring a shortage!

As future breakthroughs in healthcare are reported, doctors and the news media are going to spin the story endlessly to their own ends. It’s going to take an astute, internet-savvy, adept citizenry to recognize that the emergence of significant research throughout the world is now focused and published on resveratrol. These recent resveratrol studies are on a par with Alexander Fleming’s discovery of penicillin or Louis Pasteur’s use of heat to destroy pathogenic bacteria (Pasteurization).

Significance of Resveratrol

Resveratrol will change the world for the better, but only if the public can navigate through the conflicting interpretations by doctors and news reporters. Resveratrol is a potent anti-bacterial, anti-viral, anti-fungal, anti-inflammatory, anti-cancer, anti-estrogen, anti-cholesterol, weight-controlling, blood pressure and blood sugar-normalizing agent. The drug companies know what resveratrol portends – the end of their charade that different drugs are needed for each disease and that synthetic molecules work better than nature. This is riveting food for thought.

Resveratrol Activates a Longevity Gene (Anti-Aging)

In a widely publicized report, researchers at Harvard Medical School and BIOMOL Laboratories have demonstrated that resveratrol activates a “longevity gene” by activating a cell’s survival defense enzyme, which prolongs the time cells have to repair their broken DNA.

One of the known causes of aging and death is that older cells lose their ability to perfectly replicate DNA in every new cell. DNA “mistakes” accumulate and allow little pieces of DNA to become active and print themselves out, so to speak, creating a type of “DNA debris” that eventually stops a cell from functioning effectively. It is similar to printing out a report and having a couple of pages at the end not contain any relevant information-so you throw them away. The cell can’t throw away the extra “printed out” DNA; it accumulates and clogs up the cell. This build up of “debris” is connected to aging, and the death of individual cells. Resveratrol reduces the frequency of “DNA debris” by 60% through the longevity gene that is stimulated. [25-27, 11, 16]*

Resveratrol’s ability to activate the gene has to do with its chemical structure, not its antioxidant potential. It works by increasing the rate of a reaction known as “deacetylation.” Acetylation reactions affect whether a gene is “off” or “on.” This is extremely important. In cancer cells, for example, genes are activated that aren’t supposed to be and vice versa. By controlling deacetylation and augmenting the longevity gene, resveratrol is able to confer some serious life extension benefits-at least in the laboratory organisms.

Resveratrol and Cancer

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. [11-13]*

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. [14-17]*

Some of the latest information reveals that resveratrol causes a unique type of cell death (cell apoptosis),[11] and kills cancer cells whether they do or do not have the tumor suppressor gene,[18] it also works whether cancer cells are estrogen receptor-positive or negative.[15,19]*

Researchers in Austria have done elaborate studies showing that resveratrol blocks the ability of cancer cells to metastasize to bone (30-71%). [20] Effective in-vitro research results were reported for pancreas, breast, renal, prostate and colon cancers. All research with human-derived tumors are conducted in-vitro or in life extension research terms, ex-vivo. This means the tumor cells of a specific type of human cancer are grown in cell culture and compounds such as resveratrol are studied to determine the effectiveness in cell killing activity (cell apoptosis). In vitro refers to the cell culture techniques and ex-vivo refers to human cancer cell lines being used for the investigational research study.

Resveratrol also acts against a component of Western diet that promotes cancer cell growth: linoleic acid. Linoleic acid is converted to arachidonic, which is converted to hormone-like substances (such as prostaglandin E2 and leukotriene B4) that can promote inflammatory processes that stimulate cancer cell growth, among other things. Resveratrol specifically inhibits the enzyme cyclooxygenase-2 (COX-2) to reverse inflammation. It has been demonstrated that the western diet can cause colon cancer in rodents without any other chemical or factor being necessary.[21] In a study from Japan, resveratrol in an amount easily obtained by supplementation, inhibited the growth of breast cancer cells, and blocked the growth-promoting effects of linoleic acid from the Western diet.[22]*

Resveratrol works against a wide range of cancers, both at the preventive and treatment stages. Its ability to stop cancer is connected to its capability, first, to distinguish a cancer cell from a normal cell. Unlike chemotherapeutic drugs that
Cancers Inhibited by Resveratrol According to published research*

Colon
Neuroblastoma
Esophageal
Breast (all types)
Prostate (all types)
Leukemia (various types)
Non-Hodgkins Lymphoma
Metastasis to bone
Skin
Pancreas
Ovarian
Melanoma
Liver
Lung
Stomach
Oral
Cervical
Lymphoma (various types)
Thyroid

*In laboratory animals and/cell culture

Resveratrol and Heart/Blood Vessels

One of the serious complications of free radical damage is hardening and thickening of the 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.[1] Resveratrol is being investigated for effectiveness as treatment for this progressive process. The Heart Institute of Montreal, Canada has published research demonstrating that reseveratrol lowers blood pressure. This is an exciting area of interest in cardiovascular research. 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. [2] 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.

Finally, resveratrol also stops the proliferation of cells in the blood vessels that narrow the arteries,[3] and it also keeps blood cells from sticking together.[4] 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. [5]*

Resveratrol and Alzheimer’s Disease

Alzheimer’s patients produce an abnormal peptide (a piece of protein) known as “beta-amyloid” in their brains. Beta-amyloid provokes oxidative stress, and eventually cells are killed because of the abnormally high levels of free radicals. The killing of brain cells causes the gradual decline in Alzheimer’s patients. It has been proven that resveratrol can protect the brain against oxidative stress, and keep cells alive.[6,7]

Resveratrol and Spinal Cord Injury/Stroke

A recent study by Chinese researchers is notable. [9] If confirmed by other researchers, it 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.

The 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 protected against free radicals, when injected immediately after injury. Besides helping to ameliorate this type of injury through free radical blockage, 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.[10] Less motor damage, and less brain damage occurred post-stroke.*

Resveratrol and Diabetes

In November 2007, a study was released in the publication Cell that indicated that resveratrol administered orally to mice protected them from gaining weight and developing diabetes. A lead researcher of the study, Johan Auwerx, said a study of men and women from Finland revealed that resveratrol will likely produce similar results in humans.

Resveratrol and Antiviral Effects

A Northeastern Ohio Universities College of Medicine Study found that multiple viral protein products were reduced or completely blocked, as well as a reduction in viral DNA production. [29]

A cell culture study found that resveratrol blocked the influenza virus from transporting viral proteins to the viral assembly site, hence restricting its ability to replicate. The effect was 90% when resveratrol was added six hours after infection and continued for 24 hours thereafter. [30]


Resveratrol and Athletic performance

Dr. Auwerx (November 16, 2006) New York Times [28] States that resveratrol converts the structure of muscle to that of a trained athlete without the training.
Dr. Auwerx attributes this in large part to the significantly increased number of mitochondria he detected in the muscle cells of treated mice.

Mitochondria are the organelles in the body’s cells that generate energy, specifically the energy molecule, adenosine tri-phosphate (ATP). The reseveratrol-fed mice, with extra new mitochondria, were able to burn more fat as a fuel source, thus avoid weight gain, and decreased sensitivity to insulin. This means they tolerated carbohydrates more effectively and had an improved glucose tolerance factor.

An ordinary laboratory mouse will run one kilometer on a treadmill before collapsing from exhaustion. However, mice given resveratrol, run twice as far. They also have energy-charged muscles and a reduced heart rate, just as trained athletes do, according to an article published online in CELL by Johan Auwerx and colleagues at the Institute of Genetics and Molecular and Cellular Biology in Illkirch, France. This is the germinal research addressing the impact of resveratrol in enhancing physical endurance and performance.

Conducting your own Resveratrol evaluation

We encourage you to perform your own validation of resveratrol and its published research. The United States government website for research is www. pubmed. gov. In-put resveratrol in the search line: There are over 2,200 published research reports, emerging from major medical centers and universities throughout the world.

Referenced Research

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

2.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

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

4.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.

5.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.

6. Draczyska-Lusiak, B. et al. Oxidized lipoproteins may play a role in neuronal cell death in Alzheimer disease. Mol. Chem. Neuropathol. 1998;33:139-48

7. Jang J.H. et al. Protective effects of resveratrol on beta-amyloid-induced oxidation PC12 cell death. Free Radic. Boil. Med. 2003:34:1100-10.

8. Chanvitayapongs, S. et al. Amelioration of oxidative stress by antioxidants and resveratrol in PC12 cells. Neuroreport 1997:8:1499-502

9. Yang, Y.B. et al. Effects of resveratrol on secondary damages after acute spinal cord injury in rats. Acta. Pharmacol. Sin. 2003;24:703-10.

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

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

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

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

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

15. 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.

16. 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.

17. 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.

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

19. 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.

20. Ulsperger, E. et al. Resveratrol pretreatment desensitizes AHTO-7 human osteoblasts to growth stimulation in response to carcinoma cell supernatants. Int. J. Oncol. 1999;15:955-59.

21.Lipkin, M. et al. Dietary factors in human colorectal cancer. Annu. Rev. Nutr. 1999;19:545-86

22.Nakagawa, H. et al. Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator. J. Cancer Res. Clin. Oncol. 2001;127:258-64.

23. Zhung, H. et al. Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann. N.Y. Acad. Sci. 2003;993:276-86

24. Floreani, M. et al. Oral administration of trans-resveratrol to guinea pigs increases cardiac DT-diaphorase and catalase activities, and protects isolated atria from menadione toxicity. Life Sci. 2003;72:2741-50.

25. Ferguson, L.R. Role of plant polyphenols in genomic stability. Mut. Res.
2001;475:89-111.

26. Casper, R.F. et al. Resveratrol has antagonist activityon the aryl hydrocarbon receptor: implications for prevention of dioxin toxicity. Mol. Pharmacol. 1999;56:784-90.

27. Hsieh, T.C. et al. Cell cycle effects and control of gene expression by resveratrol in human breast carcinoma cell lines with different metastic potentials. Int. J. Oncol. 1999;15:245-52.

28.Wade, Nicholas (November 16 2006. “Red Wine Ingredient Increases Endurance, Study Shows”. New York Times.

29. Faith SA, Sweet TJ, Bailey E, Booth T, Docherty JJ. Resveratrol suppresses nuclear factor-kappaB in herpes simplex virus infected cells. Antiviral research 2006 Jul 14 PMID 16876885

30. Palamara AT, Nencioni L, Aquilano K et al. Inhibition of influenza A virus replication by resveratrol. Journal of Infectious Diseases May 2005 15; 191
(10): 1719-29. PMID 15838800