Resveratrol - many actions against cancer
Resveratrol is a polyphenolic compound with new research studies almost appearing daily. Experts already claim it can help you beat cancer - from brain tumours to breast, colon, prostate cancers and many more. It is also claimed to help in Dementia and Alzheimer´s, heart disease and even weight loss.
Resveratrol, being produced by red grape skins in response to attack by bacteria and moulds, is an important part of the reason red wine has held strong health connotations over the years. Indeed, it is now thought to be a part of the extremely important combination with grape seed extract in the answer to what is called the French Paradox. Research shows that the French consume more fat and alcohol per head than any other nation, yet have LOWER rates of heart disease and cancer. Research inside France showed that the ´epicentre´ of fat and wine consumption was Gascony, around Toulouse. And who has the least cancer and heart disease in France? The Gascons.
Why? The answer lies in the high levels of the many plant compounds they also consume - each with colourful bioactive pigments that ´protect and correct´. One important combination lies in the wine they drink - in the grape seeds and the polyphenols of the grape skins.
Over the last decade, a number of top Medical schools and cancer centres have researched resveratrol. The VITAL study in 2012 concluded that grape seed extract was the top antioxidant commonly available.
It used to be the case that most studies on resveratrol were limited to animal studies only but that has all changed:
In 2008 when a new study was published, involving a major collaborative exercise on human consumption, between Rafael de Cabo, Ph.D. at the National Institute on Aging (NIA), David A. Sinclair, Ph.D. at Harvard Medical School and 13 other worldwide institutions (Cell Metabolism; July 3rd 2008). They confirmed its many health benefits.
Memorial Sloan-Kettering, the American pillar of cancer treatment, conducted research on the inflammatory effects on cells leading to cancer. It is widely known that an enzyme, COX-2, lies behind the stimulation of localised hormones (eicosanoids) causing inflammation, the precursor to cancer. In the research Resveratrol completely turned off the COX-2 driver. MD Anderson´s studies have shown this same anti-inflammatory benefit too. Plus, after conversion in the liver to a sulphated form the compound can attack several of the steps in the cancer process even killing cancer cells.
The excitement continued when it was found how resveratrol worked directly as an anti-cancer compound: Resveratrol has been shown to be attacked by an enzyme unique to pre-cancerous and cancer cells - the cytochrome P450 enzyme, CYP 1B1. The converted compound is a toxic substance (piceatannol) which brings about cell death. Resveratrol has been dubbed a pro-drug as a consequence (Br J Cancer, 2002; 86: 774-778). Much work has been added to this by Professors Potter and Burke in the UK as they look into Salvestrols - natural compounds in certain foods that can stop the development of cancer.
Over the last decade there have been a number of studies on resveratrol and its abilities to stop the re-growth of cancer stem cells. These cells may well lie at the core of most tumours and there is currently no chermotherapy that can deal with them. However National Cancer Institute researchers showed certain bioactive natural compounds could stop their re-growth.
According to Pandy PR et al (Breast Cancer Res Treat. 2011 Nov 30 (2) 387-98) resveratrol has an anti-tumour effect with various types of cancer, being able to induce cancer cell death (apoptosis) in the cancer stem-like cells through altering the cells´ death coding.
Several studies have confirmed that cancer stem cells can proliferate and self-renew extensively due to their ability to generate anti-cell death and even drug-resistant proteins. Research by Shankar S. Nall D, Tang S-N, Meeker D, Passarini J et all (2011) showed resveratrol inhibits human pancreatic stem cells and concluded resveratrol could be used in the management of pancreatic cancer.
According to the American Association of Cancer Research, resveratrol may be an important agent for prostate cancer treatment (Dept of Urology and Biochemistry, Mayo Clinic, 1999). Resveratrol inhibits androgen action and represses certain androgen genes., so it inhibits androgen-stimulated cell growth and gene expression.
There were other studies showing that resveratrol could work with the immune system to inhibit blood supply to prostate tumours ( Greehey Children´s Cancer Research Institute, San Antonio, Texas)
And for breast cancer too - the New York Medical Collegein Valhalla) published research in 2011 showing resveratrol, and a metabolite triacetyl-resveratrol, can inhibit breast cancer, whether oestrogen positive or negative (International Journal of Cancer Jan 2011)
Several studies show that resveratrol’s action seems to be dose and duration dependent. At low doses it may encourage adult stem cells and cancer stem cells to re-grow but at higher doses, resveratrol inhibits cancer stem cell renewal.
A combination of red grape polyphenols at relatively low doses can be effective at preventing breast cancer from progressing to become an advanced disease, according to a study by S. F. Dharmawardhane of Universidad Central del Caribe School of Medicine in Bayamon, Puerto Rico (pub.Translational Oncology). The research then looked at the use of these polyphenols and showed they enhanced drug action against breast cancer: RQC (resveratrol, quercetin and catechin) treatment inhibits breast cancer progression and may potentiate anti-EGFR therapy by inhibition of Akt/mTOR signaling. The research even recommended supplementation.
According to various M D Anderson studies, Resveratrol improves chemotherapy success and reduces side-effects; it also increases glutathione levels which help oxygenate and restore healthy cells. (Oxygen kills cancer cells).
The action in improving chemotherapy, has been repeated with Radiotherapy at the University of Missouri. Resveratrol has been shown also to increase levels of two naturally occuring anti-cancer proteins (perforin and granzyme B) throughout the body, aiding the body´s fight against any cancer but particularly prostate cancer.
Other studies have shown Resveratrol improved survival in gliomas. breast and prostate cancer patients, because it repaired the p53 gene which in turn repaired DNA and caused cancer cell death. It seems to have anti-tumour and anti-vascular proliferation effects (tumours need their own blood supplty and it can stop this). And it stops metastatic action. So it doesn´t do much then?!
Reseach has also shown a strong synergistic effect with curcumin and quercitin in anti-cancer studies. Detailed research studies are listed at the bottom of this article. These various research studies are available in more detail in Cancer Watch.
Resveratrol has now caught the eye of several large pharmaceutical companies who are already trying to capture its benefits in a synthetic, patentable form - a new ´weight-reducer´ resveratrol pill is almost with us!
This natural compound, a phytoalexin, produced by certain fruits to defend the fruit cells from attack by fungi and moulds, does have significant and varied benefits but much of the research is very recent having taken place over the last few years, so Resveratrol´s benefits are not widely known, while, as usual, mis-information and over-claim abound. One source of several studies was even found to be fabricating results!
Do we think it is a cancer ´cure´? No. At CANCERactive we think no single compound (Drug or natural) is likely to be a cure for cancer. However it may well be useful as part of your overall programme.
What is resveratrol?
Resveratrol (3,4´,5-trihydroxystilbene) is a natural phenolic compound found in trans- and cis- forms. There is a lot of excitement (and thus research and web pages) about the trans- form, but little known on the benefits of the cis- form.
Both forms are found in the skins of a number of fruits and plants, where its prime function is to protect against potential invaders like moulds and fungi. The largest concentrations are found in red grape skins with about 10 per cent of these levels also occurring in blueberries and bilberries and even smaller amounts in raspberries and blackberries. Many people have lauded resveratrol as the major health benefit component of red wine. A little understanding is however needed on this subject.
The Red wine ´story´ - Red wine is produced with the wine being made on the grape skins and certain types of wine - particularly from damper areas of the globe can contain up to 3 mgs of resveratrol per litre. However, white wine and champagne are produced having separated off the skins so contain little of this compound. Worse, the use of modern pesticides and fungicides has reduced the need for defensive resveratrol in the grape skin because it seems to be produced in response to the attack. So you get the double negative whammy less resveratrol and a pesticide contaminated end product if you don´t drink an organic wine.
Worse certain wine countries are looking at GM grapes which will be mould resistant. Less and less of this beneficial compound may appear in bottles of mass-produced red wine in the future. Resveratrol is also damaged by light and oxygen, so keeping the red wine on brightly lit supermarket shelves doesnt help either, nor drinking a glass of wine in a restaurant which opened the bottle yesterday!
Sources: Red grapes are certainly not the only good source. For example, blackberries (black raspberries) provide a powerful mix of cancer-inhibiting compounds according to new research from the Ohio State University Cancer Center.
Rats injected with oesophageal cancer inducing factors were divided into two groups. The group eating black raspberries after two weeks had 60 per cent less cancers and the researchers concluded that the berries protected the genome from damage.
Indeed, the researchers described the results as astonishing. Having measured the gene activity in the rats, while 50 per cent altered due to the cancer induction in the normal group, 20 per cent less were altered in the group taking the berries.
Lead researcher Gary Stoner felt that these results must derive from a number of natural compounds in the fruit. But then that is exactly what we keep telling you at CANCERactive: Cancer is a multistep process and to tackle it you need to tackle the various steps and stages. Some natural compounds may work well on one step, while others work on other steps.
Research studies usually use concentrations of the compound above 20 mgs and there is little research on its safety at higher levels. Supplements frequently use resveratrol from plants and herbs other than grape skins notably Polygorum Cuspidatum.
General Benefits of Resveratrol
From Research studies the benefits include include:
Yeast and Fungal infections
Not surprisingly, since resveratrols prime function in nature is to protect the sugary flesh of the fruit against moulds, fungi and yeasts, a study in Arch Pharm Res. 2005 May;28(5):557 found potent anti-fungal activity in the human body with resveratrol. This included destruction of candida albicans.
Another study showed that administering resveratrol immediately after influenza infection, stopped the virus from replicating by altering certain factors in the potential host cells of the human body (Journal of Infectious Diseases May, 2005).
A study in the American Journal of Physiology (Lung Cell Mol Physiol. 2004 Jun 4) using resveratrol in conjunction with quercitin showed that they stopped the enzyme production, particularly of cytokines, that could lead to inflammation in cells. Importantly they did not interfere with the simultaneous activity of Tamoxifen, nor did Tamoxifen interfere with their activity, showing they could be taken simultaneously. This has implications for inflammatory diseases and particularly cancers like breast cancer.
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Anti-ageing and calorie restriction
One of the most interesting developments has come in the area of calorie restriction. The Okinawans have the longest life expectancy in the world. One of the major reasons for this (apart from their high mineral and low sodium intakes) is calorie restriction they consume up to 40 per cent less calories than even the Japanese of 50 years ago.
This is not the first time calorie restriction has been noted as a factor in longevity. The Norwegians had their food supplies dramatically reduced by the occupying German Military during the Second World War, yet their restricted diets of fish and lowered calories resulted in a 35 per cent overall health improvement.
Research studies with rats show that calorie deprivation results in increased longevity: A 10-30 per cent reduction can almost double their life span. Harvard Researchers (icon 2. 2007) have even released a video explaining how cutting the food intake of any organism by 30-40 per cent can increase longevity.
Calorie restriction has a number of benefits:
The end benefit is that the body is slimmer and leaner. Fat is a wonderful solvent. If you have fat stores around your body, they will hold toxins, chemicals and hormones you would rather excrete.
Calorie restriction reduces metabolic rate. Your Power stations, or mitochondria, are not required to work as hard or burn as much fuel, so less waste products, toxins and free radicals are produced.
Calorie restriction reduces insulin production, and this reduces the risks of both diabetes and cancer. IGF-1 levels are also lowered in the body IGF-1 can cause the rapid multiplication of cells.
But the important ´added discovery´ is that calorie restriction increases the body´s stress response-increasing survival hormones and, along with this, the body´s ability to repair DNA and heighten cellular efficiency.
There have been a number of important research studies conducted by Harvard Medical School on nematodes, fruit flies and mice most notably the study (Nature 2006;444:337-342) by Harvard and others using small mice. In this Resveratrol increased longevity by stimulating the survival defence enzyme Sir, which in turn stimulates the production of sirtuins , survival defence hormones produced when animals are on restricted calorie diets. And in turn, this improved insulin sensitivity and reduced IGF-1 levels, increased mitochondrial numbers and activity, and improved motor function. Moreover it negated the detrimental effects of a high-calorie diet at a genetic level.
However the doseage used was 24 mgs per kilogram of body weight equivalent to 1000 bottles per day of red wine!
Not surprisingly there are also scientific studies that show a restriction of calories can stop tumour growth. Drugs based on resveratrol are being studied for both anti-ageing and type-2 diabetes. But whilst Pharmaceutical companies are working on drugs to increase your longevity, your diabetes and cancer risks, your eat-to-beat cancer strategy can be improved by the knowledge that sirutins are crucial and they can be significantly stimulated by resveratrol.
The latest and most important study from the NIA, Harvard and the 13 worldwide centres, enhanced all these antiageing findings. Crucially, it seems keep you living younger, longer! And importantly for the overweight and obese, it seems to cancel out the negative effects of a poor diet as the benefits were equal whether the mice were on a normal diet or a calorie-rich one!!
Specific conclusions included:
Resveratrol supplementation improves cardiovascular health and reduces fatty changes in the liver.
Resveratrol supplementation prevented age- and obesity-related decline in cardiovascular function.
Resveratrol supplementation significantly lowered total cholesterol and inflammation.
Resveratrol supplementation increased the functioning of blood vessels significantly.
Resveratrol supplementation seemed to result in better bone health.
Resveratrol supplementation reduced cataract formation, and enhanced balance and motor coordination.
So, how do you live younger, longer? Eat lots of organic dark red or black fruits and, if you cant, supplement! Remember, it is likely that pesticide-sprayed or GM fruits will not produce significant quantities of resveratrol, as they have little need to naturally protect themselves from fungal attack.
Dementia and Alzheimers
One of the biggest problems in Alzheimers is the build up of beta-amyloid peptides which destroy brain cells. A moderate red wine consumption has been found to correlate with lowered risk of Alzheimers. According to the University of Basel in a study on cell cultures resveratrol increases cell viability through offering neuro-protective and anti-oxidative benefits by enhancing the free-radical scavenger glutathione.
A disease that is increasingly common in the elderly, macular degeneration seems to be caused by the action of free radicals on the retinal repair cells, Research from the Food Group at Ohio State University (R. King) has shown that resveratrol can combat this.
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The World Health Organisation has suggested that resveratrol can reduce cardiovascular risks by up to 40 per cent. It blocks platelet stickiness by blocking the aggregating factors, it prevents oxidation of Low Density Lipoprotein (LDL) and reduces tri-glyceride and cholesterol levels. Most importantly, it appears to reduce tension levels and can relax and dilate the arteries.
Apart from the anti-cancer benefits mentioned above:
MD Anderson have researched resveratrol extensively and shown in a number of studies that resveratrol can be a potent force as a preventive and chemotherapy agent. They concluded that it suppresses cell proliferation in a wide variety of tumour cells, including lymphoid and myeloid cancers; multiple myeloma; cancers of the breast, prostate, stomach, colon, pancreas, and thyroid; melanoma; head and neck squamous cell carcinoma; ovarian carcinoma; and cervical carcinoma. They have found it to work at a number of levels, for example suppressing enzyme and protein production, suppressing cytokine production, suppressing Cox-2 and the formation of bad eicosanoids, stimulating glutathione, and blocking various carcinogenic processes. It seems to concentrate in the liver and kidneys and is converted to a sulphated form which then blocks the process of cancer at a number of stages. They have even found it to have therapeutic effects. It can block the damaging effects of a linoleic acid-rich diet. MD Anderson have concluded that it has a huge potential for fighting cancer and it can also improve the success rates of chemotherapy, appearing safe even in high doses.
In studies with breast cancer and astrocytoma (brain tumour) cells, resveratrol has been shown to induce cancer cell death (apoptosis) via p53 pathways. P53 is the gene that repairs DNA. (Laux MT, Cornell University)
In studies with resveratrol and curcumin (Anticancer Research 2004 March), these two natural compounds seem to stop tumour cell growth and induce cancer cell death in neuroblastomas by activating the p53 gene pathway.
In a study of gliomas (Brain tumours) using rats (Clin Cancer Res. 2004; Mar) a concentration of resveratrol at 40 mgs per kilogram of body weight per day increased survival rate, by exerting an anti-tumour effect and an anti-vascular effect. It was concluded that the natural compound is a potent chemotherapy agent.
In studies on Neuroblastomas (brain tumours) in mice resveratrol appears to stop cellular proliferation, and alters the cellular structure of the tumour cells leading to cell death. It exerted clear ant-tumour effects (Surgery, 2004, July)
MD Anderson looked into resveratrol in combination with genistein for their effects with prostate cancer. Prostate cancer is driven through an Androgen Receptor pathway, and these two natural compounds suppressed the pathway at high concentrations. Alabama University have concluded in tests on mice that it can be hugely protective against prostate cancer development, and also with female mice and breast cancer.
- An Austrian study showed that resveratrol could prevent metastasis forming in the bones, from primary tumours elsewhere.
New research suggests it could be an important help in fighting prostate cancer.
Previous research has shown that resveratrol can boost the effectiveness of prostate cancer chemotherapy. Research in the Annals of the New York Academy of Sciences 2011, concluded that resveratrol is a powerful ´chemosensitiser and it actually helps prostate tumours respond more effectively to chemotherapy treatment by enhancing signaling molecules. Resveratrol also seems to increase levels of proteins that fight malignant cells. Michael Nicholl, an assistant professor of oncology at the University of Missouri School of Medicine, and his team have shown resveratrol has the same benefits if used with radiotherapy.
The researchers found that resveratrol boosted levels of two naturally-occurring proteins: Perforin and granzyme B. Interestingly, these proteins can target any and all malignant cells throughout the body.
Resveratrol seems to produce even more of these proteins when the tumour is that of prostate cancer.
It is critical that both proteins, perforin and granzyme B, are present in order to kill the tumour cells, and we found that the resveratrol helped to increase their activity in prostate tumour.
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So resveratrol is becoming a wonder natural compound. Its powers include:
Anti-fungal, anti-yeast, anti-viral
Antioxidant promotes glutathione
Protects against Heart disease, Alzheimers and type-2 Diabetes
Protects DNA, stimulates repair genes
Protects against cancer
Kills cancer cells. Prevents metastasis
Aids Chemotherapy results, whilst protecting healthy cells
To repeat, much of this is very, very new research and studies with humans are minimal. The levels of supplementation are unclear, although high doses seem safe.
If you are thinking of supplementing with Resveratrol, you might like to consider the specially selected Product of Choice, from Natural Selection. Click here to find out more. And if you are thinking supplementing with Curcumin click here for the Natural Selection "Product of Choice"
Other articles of interest:
Grape seed extract: CLICK HERE to read
Turmeric/Curcumin: CLICK HERE to read
The Rainbow Diet - and how it can help you beat cancer. CLICK on link above
Resveratrol as a drug in Concentrate
Please be clear: At CANCERactive we do not consider the above compound to be a cure for cancer, despite what the research says or experts doing the research may claim. The above, is an article on the compound from published research and expert opinion in the public domain. At CANCERactive we do not believe that any single compound (drug, vitamin, whatever) is a cure for cancer. We believe that people can significantly increase their personal odds of survival by building an Integrated Programme of treatments. Equally, cancer prevention is best practiced through a width of measures.