Secrets Behind Resveratrol’s Health Benefits

Scripps Florida Scientists Reveal Molecular Secrets Behind Resveratrol’s Health Benefits

29 April 2014 The Scripps Research Institute

Resveratrol Molecule, Grapes, Red WineResveratrol has been much in the news as the component of grapes and red wine associated with reducing “bad cholesterol,” heart disease and some types of cancer. Also found in blueberries, cranberries, mulberries, peanuts and pistachios, resveratrol is associated with beneficial health effects in aging, inflammation and metabolism.

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have now identified one of the molecular pathways that resveratrol uses to achieve its beneficial action. They found that resveratrol controls the body’s inflammatory response as a binding partner with the estrogen receptor without stimulating estrogenic cell proliferation, which is good news for its possible use as a model for drug design.

The study was recently published as an accepted manuscript in the online journal eLife, a publication supported by the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust.

“Estrogen has beneficial effects on conditions like diabetes and obesity but may increase cancer risk,” said Kendall Nettles, a TSRI associate professor who led the study. “What hasn’t been well understood until now is that you can achieve those same beneficial effects with something like resveratrol.”

The problem with resveratrol, Nettles said, is that it really doesn’t work very efficiently in the body. “Now that we understand that we can do this through the estrogen receptor, there might compounds other than resveratrol out there that can do the same thing—only better,” he said.

“Our findings should lead scientists to reconsider the estrogen receptor as a main target of resveratrol—and any analogues,” said Jerome C. Nwachukwu, the first author of the study and a research associates in the Nettles laboratory. “It has gotten swept under the rug.”

In the new study, Nettles, Nwachukwu and their colleagues found that resveratrol is an effective inhibitor of interleukin 6 (IL-6), a pro-inflammatory protein that is part of the immune system (although IL-6 can be anti-inflammatory during exercise). High levels of IL-6 are also associated with poor breast cancer patient survival. According to the study, resveratrol regulates IL-6 without stimulating cell proliferation by altering a number of co-regulators of the estrogen receptor.

In addition to Nwachukwu and Nettles, other authors of the study, “Resveratrol Modulates the Inflammatory Response via An Estrogen Receptor-Signal Integration Network,” include Sathish Srinivasan, Nelson E. Bruno , Travis S. Hughes, Julie A. Pollock, Olsi Gjyshi, Valerie Cavett, Jason Nowak, Ruben D. Garcia-Ordonez , Patrick R. Griffin, Douglas J. Kojetin and Michael D. Conkright of TSRI; Alex A. Parent and John A. Katzenellenbogen of the University of Illinois; and René Houtman of PamGene International, The Netherlands. For more information, see http://elifesciences.org/content/early/2014/04/24/eLife.02057

The study was supported by the National Institutes of Health (grants PHS 5R37DK015556; 5R33CA132022, 5R01DK077085, 1U01GM102148, R01DK101871 and F32DK097890), the Ballen Isles Men’s Golf Association, the Frenchman’s Creek Women for Cancer Research, the State of Florida and the James and Esther King Biomedical Research Program, Florida Department of Health (1KN-09).

http://www.scripps.edu/news/press/2014/20140428nettles.html

Full bibliographic information eLife 2014;10.7554/eLife.02057, published April 25, 2014.
Authors:
Jerome C Nwachukwu, 1; Sathish Srinivasan, 1; Nelson E Bruno, 1; Alex A Parent, 2; Travis S Hughes, 1; Julie A Pollock, 1; Olsi Gjyshi, 1; Valerie Cavett, 1; Jason Nowak, 1; Ruben D Garcia-Ordonez, 1; René Houtman, 3; Patrick R Griffin,1; Douglas J Kojetin, 1; John A Katzenellenbogen, 2; Michael D Conkright, Kendall W Nettles, 1.

Red Wine Chemical Resveratrol Remains Effective Against Cancer

Red Wine Chemical Remains Effective Against Cancer

After The Body Converts It

 

02 October 2013 Leicester, University of

Resveratrol Red Wine SourceA chemical found in red wine remains effective at fighting cancer even after the body’s metabolism has converted it into other compounds.

This is an important finding in a new paper published in the journal Science Translational Medicine by Cancer Research UK-funded researchers at the University of Leicester’s Department of Cancer Studies and Molecular Medicine.

The paper reveals that resveratrol – a compound extracted from the skins of red grapes – is not rendered ineffective once it is metabolised by the body.

This is an important development, as resveratrol is metabolised very quickly – and it had previously been thought that levels of the extracted chemical drop too quickly to make it usable in clinical trials.

The new research shows that the chemical can still be taken into cells after it has been metabolised into resveratrol sulfates.

Enzymes within cells are then able to break it down into resveratrol again – meaning that levels of resveratrol in the cells are higher than was previously thought.

In fact, the results appear to show resveratrol may be more effective once it has been generated from resveratrol sulfate than it is if it has never been metabolised because the concentrations achieved are higher.

The team, led by University of Leicester translational cancer research expert Professor Karen Brown, administered resveratrol sulfate to mice models.

They were subsequently able to detect free resveratrol in plasma and a variety of tissues in the mice.

This is the first direct sign that resveratrol can be formed from resveratrol sulfate in live animals, and the researchers think it may help to show how resveratrol is able to have beneficial effects in animals.

The study also showed that resveratrol generated from resveratrol sulfate is able to slow the growth of cancer cells by causing them to digest their own internal constituents and stopping them from dividing.

Professor Karen Brown said: “There is a lot of strong evidence from laboratory models that resveratrol can do a whole host of beneficial things – from protecting against a variety of cancers and heart disease to extending lifespan.

Grapes - Source of Resveratrol“It has been known for many years that resveratrol is rapidly converted to sulfate and glucuronide metabolites in humans and animals  – meaning the plasma concentrations of resveratrol itself quickly become very low after administration.

“It has always been difficult to understand how resveratrol is able to have activity in animal models when the concentrations present are so low, and it has made some people skeptical about whether it might have any effects in humans.

“Researchers have hypothesized for a long time that resveratrol might be regenerated from its major metabolites in whole animals but it has never been proven.

“Our study was the first to show that resveratrol can be regenerated from sulfate metabolites in cells and that this resveratrol can then have biological activity that could be useful in a wide variety of diseases in humans.

“Importantly, we did all our work with clinically achievable concentrations so we are hopeful that our findings will translate to humans.

“Overall, I think our findings are very encouraging for all types of medical research on resveratrol. They help to justify future clinical trials where, previously, it may have been difficult to argue that resveratrol can be useful in humans because of the low detectable concentrations.

“There is considerable commercial interest in developing new forms of resveratrol that can resist or overcome the issue of rapid metabolism. Our results suggest such products may not actually be necessary to deliver biologically active doses of resveratrol to people.”

Dr Sarah Williams, Cancer Research UK health information officer, said: “This interesting study  supports continued research into resveratrol as a therapeutic molecule, but it’s important to note that any benefits from the molecule don’t come from drinking red wine. It’s well established that drinking any type of alcohol, including red wine, increases the risk of developing cancer.”

The study was carried out over eight years, and was funded by the Cancer Research UK and National Institute for Health Research (NIHR) Experimental Cancer Medicine Centre in Leicester, and the US National Cancer Institute.

 

Attached files

Professor Karen Brown of the University of Leicester Department of Cancer Studies and Molecular Medicine.

Resveratrol Soon To Be In A Phamaceutical For You

From Alliance For Natural Health

Big Pharma is drooling over the prospect of getting it all to themselves.

 

Resveratrol, a substance found in the skin of red grapes as well as in pomegranates and Japanese knotweed, has been a popular dietary supplement for many years. It has anti-inflammatory and antiviral properties, possibly the potential to extend life, prevent several different cancers, protect the heart, ameliorate common diabetes symptoms, and control plaque in the brain and otherwise help with Alzheimer’s disease. And that isn’t even a complete list. It’s clear why drug companies are excited.

 

Resveratrol is widely available as a dietary supplement—but may not be for long if we are not vigilant. A new study has thrown the excitement over resveratrol into high gear. Results from ten years of research have just been published by David Sinclair, a Harvard Medical School genetics professor and the study’s senior author. The research validated earlier findings that resveratrol may protect against age-related diseases because it turns on the SIRT1 gene that recharges mitochondria.

 

Sinclair’s earlier research was partly discounted by other scientists in 2009 and 2010. They suspected that resveratrol might only seem to activate the SIRT1 gene because studies used a synthetic fluorescent chemical to track the effect. Since these synthetic chemicals are not found in nature, they reasoned, the experiment is not reproducible in humans. In this study, however, Sinclair used naturally occurring amino acids to track the benefits, which affirmed the compound’s benefits.

 

Sinclair is not a disinterested party. He is the founder of Sirtris Pharmaceuticals, which focuses on developing resveratrol drugs, that is drugs that will mimic resveratrol’s effects with new and thus patentable molecules.

Pharmaceutical giant GlaxoSmithKline (GSK) acquired Sirtris in 2008 for $720 million. GSK subsequently abandoned its work on resveratrol-based drug SRT501 because the drug didn’t appear to work on cancer patients and worsened kidney damage. It’s likely, however, that the new findings will prompt GSK to restart its work on a resveratrol-based drug; resveratrol is already the subject of at least two dozen clinical trials.

 

Because Resveratrol is also the subject of an investigational new drug (IND) application, GSK could petition FDA to ban natural resveratrol. Yes, that’ s how warped the law is. Apply for FDA approval for something synthetic, new-to-nature, and thus potentially much more dangerous, and you can then try to ban the natural substance on which your product was based.

 

This is governed by a provision in the law, as we explained last year. There is an absolute prohibition against banning the natural substance if it is grandfathered (that is, marketed before 1994) or if the FDA has accepted a New Dietary Ingredient (NDI) notification from supplement manufacturers.

 

Supplement companies have tried to file NDIs for resveratrol, but the FDA has rejected them all, stating that an IND had already been filed, so they won’t accept an NDI. Despite resveratrol being a natural component of food and a constant part of the food supply, it may be hard to prove that it was marketed before 1994. This, of course, merely reveals the illogic of the grandfathering process: it was put in place as a means of proving the safety of an ingredient, but instead it’s being used to protect the pharmaceutical industry.

 

New drug applications (INDs) are confidential, but we can make an educated guess that Sirtris Pharmaceuticals is one of the companies that filed an IND since they have already started clinical drug trials (an IND is required before clinical drug trials). If they are successful, resveratrol will then be available in an expensive, synthetic drug form, likely requiring a prescription at a very high cost and a disease condition for access. It will be tempting for the drug company to then try to have the FDA ban the natural form of resveratrol. It is our job to prevent that by making it painful for both the company and the FDA.

 

In this context, let’s remember what happened to pyridoxamine, one of the three primary natural forms of vitamin B6. Biostratum, the North Carolina-based manufacturer of a planned pyridoxamine-based drug called Pyridorin, petitioned the FDA for market exclusivity, and FDA kowtowed, effectively prevented any substance containing pyridoxamine from being marketed as a dietary supplement. To date no drug has even appeared, so we have neither natural B vitamin nor drug, an outcome that is all too typical of FDA illogic and misuse of power. A similar petition has been filed regarding P5P, the natural form of B6 that is most bio-available. All other forms of B6 must be converted by the body to this form to be used, and without it we would all die. Is this really something to ban and make into an exclusive, prescription-only drug? (If you have not already done so, please send your message to FDA and Congress to make sure P5P remains available as a supplement.)

 

If the dietary supplement version of resveratrol becomes threatened, rest assured that ANH-USA will be with you on the front lines, fighting to maintain your access to this amazing nutritional ingredient.

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