Resveratrol Pro – The most outstanding Resveratrol based supplement currently available

Have you ever heard of the French Paradox? It’s the phrase that was coined in the 1980’s by Dr. Serge Renaud, a scientist from Bordeaux University in France, to reflect the observation that even though the French as a nation eat a diet that is relatively rich in saturated fats, they experience relatively low rates of coronary heart disease. For example, according to data from the British Heart Foundation, in 1999 rates of death from coronary heart disease among males aged 35–74 years were 115 per 100,000 people in the U.S. but only 83 per 100,000 in France! You would, of course, expect the reverse to be true - saturated fats are not good for our hearts and so you would think that the greater the consumption of these types of fats, the higher the incidence of coronary heart disease.

Many theories have been put forward to try and explain the French Paradox. In reality, it is probably a combination of a number of factors - and one of these that came to the fore in the 1990’s relates to the amount of red wine drunk by the French. And why should this be important - apart from the fact that obviously it makes life very enjoyable? Well, red wine is known to be a rich dietary source of a number of phytophenols (naturally occurring powerful anti-oxidants) including, in particular, Resveratrol And it’s Resveratrol that holds the key to unlocking part of the puzzle.

So what is Resveratrol?

Resveratrol is a naturally occurring compound that bears the chemical name 3,5,4'-trihydroxystilbene. The richest source of Resveratrol comes from the roots of the polygonum cuspidatum plant (otherwise known as Japanese Knotweed or Ko-jo-kon). It is cultivated mainly in China and Japan and is used in traditional oriental medicine to treat diseases of the blood vessels, heart and liver.

Whilst Resveratrol can also be found in other plants such as eucalyptus, spruce, and lily, and is present in foods such as mulberries, cranberries, blueberries and peanuts, our greatest dietary source of Resveratrol comes from three different grape varieties - vitis vinifera, vitis labrusca and muscadine - all of which are used to make red wine. And although Resveratrol is found in the grape vines, roots, seeds, and stalks, its greatest concentration actually occurs in the grape skin. And it is this fact that means that red wine offers greater health benefits than white wine because only red wine is fermented with grape skins.

The amount of fermentation time a wine spends in contact with grape skins is an important determinant of its Resveratrol content - the more time the grape skins are present in the fermentation process, the greater the amount of Resveratrol absorbed by the wine. Ordinary non-muscadine red wines contain between 0.2 and 5.8 mg/L of Resveratrol (1) depending on the grape variety. Red wines made from muscadine grapes may offer even greater concentrations of Resveratrol. By contrast, white wines contain lower levels of Resveratrol because they are fermented after the removal of the grape skins.

Resveratrol is synthesized by plants in response to environmental stressors such as water deprivation, UV irradiation, and, especially, fungal infection. Indeed, Resveratrol is classed as a phytoalexin, a family of antibiotic compounds produced by plants as part of their defence mechanism against disease. Since fungal infections are more common in cooler climates, grapes grown in cooler climates have a higher concentration of Resveratrol in them.

What are the health benefits of Resveratrol?

As we have touched on already, Resveratrol possesses cardio-protective benefits - in other words it’s good for your heart. Certainly the use of red wine (and therefore Resveratrol) for health purposes is not something that is new. Around 4,500 years ago, Ayurveda, the ancient medicinal book of Hindus described “darakchasava” (fermented juice of red grapes) as a cardio-tonic(2). However, it was not until 1940 that Resveratrol was first identified as the medicinal component of grapes, and by the late 20th century it had been recognized as one of the key factors that could explain the French Paradox. In 1992 the above mentioned Dr Renaud published research in the highly respected medical journal, The Lancet, in which he noted that epidemiological studies had indicated that “consumption of alcohol at the level of intake in France (20-30g per day) (could) reduce risk of CHD by at least 40%”(3).

The actual mechanism by which Resveratrol protects the heart is not yet fully understood. In his research Renaud examined the widely held view that wine was thought to provide protection against coronary heart disease by preventing atherosclerosis (the narrowing of the arteries due to the formation of plaques) through the action of high density lipoprotein cholesterol (HDL cholesterol - sometimes called the “good cholesterol”). However, he found that serum concentrations of HDL cholesterol were no higher in France than in other countries. On re-evaluating previous studies, Renaud concluded that moderate wine consumption may help to prevent coronary heart disease because it appears to inhibit platelet aggregation. Platelet aggregation refers to the clumping together of platelets in the blood and is part of the sequence of events that leads to the formation of clots (known as a thrombi - singular is thrombus). Platelet aggregation is related to coronary heart disease.

Other researchers have focused on Resveratrol’s anti-oxidant properties. Anti-oxidants are important for our health and well being as they “mop up” free radicals in our systems. Free radicals are highly unstable and react quickly with other compounds. Ultimately the instability and reactivity of free radicals disrupts living cells. Some free radicals occur during our body’s normal metabolism. Our immune systems may even specifically create them to neutralize viruses and bacteria. But environmental factors such as pollution, radiation, cigarette smoke and herbicides can also add to our free radical load. If free radical production is excessive or if anti-oxidants are not available, damage occurs. Nowadays it is recognised that the build up of free radical damage that occurs over the passage of time plays a huge part in the ageing of the human body. Therefore, it’s important that the body is well supplied with anti-oxidants.

Resveratrol is known to have powerful anti-oxidant capabilities. For example in one study the researchers concluded that “Resveratrol possesses cardio-protective effects which may be attributed to its peroxyl radical scavenging activity”.(4)

Studies have also demonstrated that Resveratrol has the ability to help protect many of the body’s vital organs including the kidneys(5), heart and the brain, from ischemic reperfusion injury. Ischemic reperfusion is the medical term given to the restoration of blood flow to an area that has previously experienced deficient blood flow. Injury due to ischemic reperfusion arises because the reperfusion can lead to oxidative stresses which in turn may cause damage to the affected tissues or organs. For example in one study involving rats that had been subjected to ischemic reperfusion researchers were able to establish that Resveratrol acted as a potent anti-arrhythmic agent with cardio-protective properties. They concluded that this may be correlated to Resveratrol’s anti-oxidant activity and its ability to regulate nitric oxide.(6)

Resveratrol and Cancer

Resveratrol’s health benefits extend into the realms of cancer prevention and treatment. In the late 1990’s researchers reported that topical applications of Resveratrol had been able to prevent the development of melanomas in mice that had been treated with a carcinogen.(7)

Since then there have been numerous studies looking into the potential for Resveratrols effectiveness in terms of cancer prevention and treatment. For example, in a study published in the March 2008 edition of the journal, Advances in Experimental Medicine and Biology,(8) researchers were able to show for the first time that Resveratrol was able to destroy pancreatic cancer cells by extinguishing the cells’ core energy source (the mitochondria). If you can stop a cancer cell’s energy supply then you are, in theory, able to stop the cancer. Pre-treatment with Resveratrol followed by irradiation therapy was found to be capable of inducing apoptosis (programmed cell death), a hugely important goal in terms of cancer treatment.

Again it may be Resveratrol’s anti-oxidant capabilities that are the key to its ability in helping in the fight against cancer. It is also thought that Resveratrol’s ability to inhibit platelet aggregation may help to prevent the migration of cancer cells. Research is on-going and our knowledge is continually growing. However, there can be no doubt that at this stage some of the results already reported look promising. In the future Resveratrol may indeed become a standard part of many cancer treatment/prevention protocols - particularly for those cancers that Resveratrol can come into direct contact with such as skin and gastrointestinal cancers.

Resveratrol and life extension.

Perhaps one of the most exciting uses for Resveratrol is in the arena of life extension. Again scientists are not yet entirely sure of the mechanisms at play but it appears that Resveratrol may offer a completely new approach to the question of aging and the diseases and conditions that accompany it. Although, as we have discussed above, scientists have known about Resveratrol’s cardio-protective properties for quite some time now, the role it may play in expanding life span is something that has only come to the fore recently.

In 2006, the results of a study that had been led by David Sinclair and Joseph Baur at the Harvard Medical School and by Rafael de Cabo at the National Institute on Aging were published in the journal Nature(9) and they caused something of a stir. The research team had discovered that Resveratrol appeared to be able to offset the bad effects of a high calorie diet and expand the life span of mice.

The researchers fed different groups of year old male mice different diets to see what the effects of diet would be and whether Resveratrol could make a difference. The significance of the age of the mice was that year old mice are middle aged in mouse terms.

One group of mice were fed a high fat diet with 60% of their calories coming from fat. Not surprisingly this group of mice soon became overweight and began to display the signs of impending diabetes with high levels of glucose and insulin in their blood streams. Their livers became enlarged and they began to die earlier than those mice that were just being fed a standard diet.

Another group of mice was fed an identical high-fat diet but this group also received a large daily dose of Resveratrol - much greater than a human could get from drinking wine. Although the Resveratrol did not stop these mice from putting on weight and becoming as fat as the other group of mice on the high fat diet, high blood levels of glucose and insulin were avoided and their livers remained at normal size. But what was even more startling was the fact that these mice did not die early like the other group of high-fat diet mice but instead lived as long as the mice on the standard healthy diet. In other words they were able to experience all the pleasure of eating high fat food without paying the price for it! Add to this the fact that the Resveratrol high-fat diet mice did as well as the mice on the standard healthy diet in terms of motor skills performance and you can begin to see why people started to get very excited about this piece of research.

The researchers were not able to say exactly why Resveratrol should have had such dramatic effects on the lifespan of the mice but they believed that the Resveratrol had either directly or indirectly activated a gene known as Sirt-1 which appears to be able to mimic the effects of calorie restriction.

Scientists have known since the 1930’s that calorie restriction is one of the keys to life extension. However, the sort of calorie restriction that we are talking about here is excessive - the relevant research involved feeding mice a diet of up to 40% fewer calories but with all the required nutrients. Such a diet resulted in a 50% increase in the life span of the calorie restricted mice over mice fed an ordinary diet. If the same were true in humans (which is an entirely plausible assumption to make), one way to extend our lives would be to adopt a similar calorie restricted diet. But in reality, how many of us would be able to keep to a diet whereby we had to reduce our calorie intake by such a drastic amount?

It could be therefore that by activating the Sirt-1 gene in humans Resveratrol may be able to provide us with the one of the keys to extending life span. By activating Sirt-1 which mimics the effects of calorie restriction, Resveratrol may be able to confer upon us all the benefits of calorie restriction without the need for following such a severe dietary regime. Not only would this open the door to longevity but it could also provide an entirely new therapeutic approach with which to tackle diseases of aging. No wonder Resveratrol has caused such a stir!

Indeed, if any clearer indication of the potential for Resveratrol were needed, you only need to look at recent activity in the pharmaceutical industry. Dr Sinclair founded a company, Sirtris Pharmaceuticals, to pioneer research in to sirtuins, a class of enzymes thought to prevent illnesses such as diabetes and Parkinson's disease, and to inhibit the processes behind ageing and obesity. Sirtuin production is increased by the Sirt-1 gene and because of Resveratrol’s ability to activate the Sirt-1 gene, Sirtris's research was firmly focused on Resveratrol. In April 2008 the pharmaceutical giant GlaxoSmithKline bought Sirtris for USD720m.

In terms of life extension, how much Resveratrol should we take?

It would be lovely to think that if we drank the right amount of red wine we would be able to supply ourselves with the right amount of Resveratrol so as to replicate the effects that the Resveratrol had on the mice in Dr Sinclair’s research. Apart from the fact that human trials have not yet been completed, the mice in Dr Sinclair’s study received a very large daily dose of Resveratrol which would equate to around 750-1500 bottles of red wine a day! Clearly then drinking red wine alone is not a practical solution and supplementation must be the way forward.

But even at this stage whilst research into what could be an incredible breakthrough in terms of human longevity and the treatment of diseases associated with aging is on-going, Resveratrol supplementation at much lower levels is gaining ground. Indeed, Dr Sinclair is an active proponent and along with his family and staff, he takes regular daily Resveratrol supplements.

Resveratrol Pro

While Resveratrol Pro captures the amazing health benefits of Resveratrol, it also harnesses the power of EGCG (epigallocatechin gallate - often referred to as green tea extract), quercetin, Vitamin E (D-alpha tocopheryl acetate) and other red wine polyphenols. This powerful formula gives Resveratrol Pro a unique place in the market place - it is more than just a Resveratrol supplement.
Below we look at EGCG, quercetin and Vitamin E in more detail and examine their undoubted health benefits.

EGCG (epigallocatechin gallate)

EGCG is a chemical compound known as a catechin that is found in green tea. Catechins (sometimes called tea flavanoids) are a family of flavonoid phytochemical compounds. Whilst they are predominantly found in green tea, smaller amounts of catechins also appear in black tea, grapes, wine, and chocolate. There are four polyphenol catechins in green tea - gallocatechin (GC), epigallocatechin (EGC), epicatechin (EC), and epigallocatechin gallate (EGCG). EGCG is the most abundant. Catechins are known to possess potent anti-oxidant capabilities.

As a result of their powerful anti-oxidant properties, catechins have been the subject of many scientific studies over recent years. The result is that we now know that regular green tea drinkers have lower chances of developing heart disease and certain types of cancer and that green tea maybe beneficial as an aid to weight loss programmes.

There is increasing evidence in particular with regard to EGCG to show that it can be of use in the prevention and treatment of a number of types of cancer including cervical, prostate, bladder and brain cancers. For example, in one very recent study published in November 2009(10), researchers were able to induce apoptosis (cell death) in human glioblastoma cells after treatment with a combination of compounds including EGCG. Human gliobalstoma is a deadly form of brain cancer that “continues to defy all current therapeutic startegies”. The researchers concluded that the results of their study demonstrated that the flavonoids used offered strong potential as therapeutic agents with which to treat this deadly form of cancer. In another very recent study(11), which focused solely on the use of EGCG, researchers were able to arrest the cell cycle and induce apoptosis in respect of certain types of human papilloma virus positive cervical cancer cell lines. The research team concluded that “that EGCG may be suitable for prevention and treatment of cervical cancer”.

It is thought that one of the reasons behind EGCG’s ability to fight against and prevent cancer is due to the fact that it is capable of binding with and inhibiting the anti-apoptotic transmembrane protein molecule Bcl-xl which has been implicated in the survival of cancer cells.

Quercetin

Quercetin is another phytochemical that acts as a powerful anti-oxidant. It’s found in particular in the skins of apples and in red onions. It is known to be able to reduce symptoms such as depression, fatigue and anxiety which plague so many of us living in today’s unrelenting world.

But not only is quercetin an anti-oxidant, it is also a natural anti-histamine, and an anti-inflammatory. Its antihistamine properties may help to relieve symptoms in those suffering from allergies and asthma. Its anti-inflammatory capabilities may help to reduce pain from disorders such as arthritis. Research has also shown that quercetin may be of use in the fight against cancer - especially prostate cancer. Therefore, men who are concerned about prostate problems can benefit from quercetin supplementation.

Vitamin E

Vitamin E is a generic term for a family of tocopherols and tocotrienols. D-alpha tocopherol acetate as found in Resveratrol Pro is a natural form of Vitamin E that means that it is more active and better absorbed than synthetic versions. It is one of the most common forms of Vitamin E to be used as a supplement.

Vitamin E is crucial to human health because not only is it a vitamin, but also because it is a potent anti-oxidant - indeed Vitamin E is the most powerful anti-oxidant in the lipid (fat) phase in the human body. It works effectively to deactivate free radicals thereby preventing the damage that these molecules can ultimately inflict upon the body if left unchecked. It also helps to prevent blood clots and blockages in coronary arteries. Research indicates that it may be significant in preventing and treating certain cancers, help to prevent chronic diseases, slow the aging process and even prevent or at least slow the development of cataracts.

Unfortunately, our bodies cannot produce their own Vitamin E - we need to obtain it from our diets. Although most people get enough Vitamin E from their diets to avoid an actual Vitamin E deficiency, many people’s diets do not contain enough Vitamin E to meet levels that are considered sufficient to gain full benefit from this powerful anti-oxidant. This is one vitamin that definitely requires supplementation.

There can be little doubt, therefore, that in light of the overwhelming scientific evidence outlined above, Resveratrol Pro’s unique and powerful blend of ingredients make it the most outstanding Resveratrol based supplement currently available.

Dosage

Take 1 to 3 capsules of Resveratrol Pro daily.

Warnings

Resveratrol Pro should not be taken by pregnant women or nursing mothers.

If you suffer from a platelet deficiency or blood-clotting problems, or you are taking blood thinning drugs you should only use Resveratrol under medical supervision.

EGCG is known to bind with the anti-cancer drug Velcade significantly reducing its bioavailability and thereby rendering it therapeutically useless. Therefore the consumption of green tea and green tea extracts is strongly contraindicated for patients undergoing treatment for multiple myeloma and mantle cell lymphoma.

References

1. Gu X, Creasy L, Kester A, Zeece M, X. Capillary electrophoretic determination of Resveratrol in wines. J. Agric. Food Chem. August 1999. 47 (8): 3223–7
2. Das DK, Maulik N. Resveratrol in Cardioprotection: A Therapeutic Promise of Alternative Medicine. MI February 2006 vol. 6 no. 1 36-47
3. Renaud S, De Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992 Jun 20; 339(8808):1523-6
4. Ray PS, Maulik G, Cordis GA, Bertelli AA, Das DK. The red wine anti-oxidant Resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radic Biol Med 1999 Jul;27(1-2):160-9
5. Bertelli AA, Migliori M, Panichi V, Origlia N, Filippi C, Das DK, Giovannini L. Resveratrol, a component of wine and grapes, in the prevention of kidney disease. Ann. N.Y. Acad. Sci. 957, 230–238 (2002)
6. Hung L, Chen J, Huang SS, Lee R, Su M. Cardioprotective effect of Resveratrol, a natural anti-oxidant derived from grapes. Cardiovasc. Res. 47, 549–555 (2000)
7. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM. Cancer chemopreventive activity of Resveratrol, a natural product derived from grapes. Science (1997) 275 (5297): 218–20
8. Sun W, Wang W, Kim J, Keng P, Yang S, Zhang H, Liu C, Okunieff P, Zhang L. Anti-cancer effect of Resveratrol is associated with induction of apoptosis via a mitochondrial pathway alignment. Adv Exp Med Biol 2008;614:179-86
9. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42
10. Das A, Banik NL, Ray SK. Flavonoids activated caspases for apoptosis in human glioblastoma T98G and U87MG cells but not in human normal astrocytes. Cancer (November 2009): NA. Doi: 10.1002/cncr.24699. PMID 19894226
11. Qiao Y, Cao J, Xie L, Shi X. Cell growth inhibition and gene expression regulation by epigallocatechin-3-gallate in human cervical cancer cells. Archives of Pharmacal Research (September 2009) 32 (9): 1309–15