What is the real secret, and how does resveratrol really work?
In one word, mitochondria.
Two recent studies (one of which was done by Sinclair himself) shed light on how resveratrol works, how it impacts oxidative stress, and how mitochondrial function holds the key to health, brain wellness, weight loss, and longevity.
In the first study, published in Nature,20 David Sinclair and his colleagues gave one group of mice a high-fat (60 percent of calories) diet. In middle age these rats all became obese, got diabetes, fatty livers, and died early.
He fed the same diet to another group of mice, but gave them resveratrol at a dose of 24 mg/kg of body weight —which is equivalent to the amount of resveratrol found in about 750 to 1, 500 bottles of wine a day.
That group still got fat, but lived longer and did not get diabetes or heart disease. They were also more agile and had more endurance than the rats that didn’t get the resveratrol. Interestingly, their cholesterol profiles didn’t improve but they didn’t get heart disease, showing that cholesterol is not the big evil we think it is.
So how does resveratrol have these effects? And what does this study on rats have to do with brain disease in
people? Let me explain how this relates to your brain. Anything
that helps your mitochondria helps your brain, and anything that improves your blood-sugar control, improves insulin resistance and also helps your brain.
How Resveratrol Works
In the study above, resveratrol produced changes associated with longer life span and produced the following biologic effects:
- Increased insulin sensitivity leading to better blood- sugar control.
- Reduced insulinlike growth factor-1 (IGF-I) levels—a molecule related to a growth hormone that promotes cancer growth.
- Increased AMP-activated protein kinase (AMPK)— a signaling system in the body that controls insulin sensitivity and can prevent diabetes.
- Increased peroxisome proliferator-activated receptor—coactivator 1 (PGC-1) activity—which is a critical signaling system that turns on genes that improves blood-sugar control and improves mitochondrial function.
- Increased the number of mitochondria produced by the cells— boosting the capacity to turn food into energy and to burn calories.
- Improved motor function, making the old rats more agile.
- And finally the resveratrol worked by opposing the effects of aging by modifying 144 out of 153 metabolic pathways, controlled by genes, many of which control mitochondrial function.
But what does this study really tell us—that aging, including much of brain aging and disease, is controlled in large part by sugar and insulin function in the body! Sound familiar?
Too much sugar in your diet causes your body to produce too much insulin. This triggers more inflammation and oxidative stress leading to mitochondrial injury.21 Mitochondrial damage, in turn, leads to even more insulin resistance. That means anything that protects the mitochondria, like resveratrol, will prevent at least part of
mitochondria, like resveratrol, will prevent at least part of
|the damage that leads to insulin resistance and hence mitigate many possible problems.|
People with genetically underperforming mitochondria, like the children of diabetics, are more susceptible to mitochondrial injury if they have a poor diet, don’t exercise, and don’t get enough of the right nutrients to protect their mitochondria.22
The next study published in Cell by Johan Auwerx,23 from the Institute of Genetics and Molecular and Cell Biology in Illkirch, France, tested much higher doses of resveratrol in mice, eighteen times as much, or 400 mg/kg of resveratrol—equal to about 360 capsules of resveratrol for a 130-pound person.
Their findings were even more dramatic. Imagine achieving the fitness of a trained athlete, staying thin, preventing diabetes and heart disease, and living to 120 years of age while eating a high-calorie, high-fat diet (and taking 360 pills a day of resveratrol!).
The rats fed the high doses of the resveratrol along with their high-calorie, high-fat diet had the following effects: 1. They did not gain weight and reduced the size of fat
cells. 2. They didn’t get prediabetes or metabolic syndrome. 3. They increased the number of energy-producing
mitochondria in muscle cells. 4. It turned up their metabolic thermostat
(thermogenesis) and increased fat burning in the
mitochondria. 5. They increased their endurance and aerobic
capacity (without exercise). 6. They maintained their cells’ sensitivity to insulin,
hence better blood-sugar control. 7. They had enhanced muscle strength and reduced
muscle fatigue. 8. They had improved coordination. 9. There were no side effects on any organs. 10. They increased the activity of PCG-1 alpha, which
in turn controls genes that improve the function of mitochondria and blood-sugar control.
This seems incredible. But it is plausible if you understand these two root causes of obesity, brain injury, aging, and disease—blood-sugar control and the health, number, and function of your mitochondria.
That taking only resveratrol even at high doses will allow us to live a depraved life of sloth and gluttony and live disease-free forever, is unlikely. But what these studies do tell us is very important.
When taken from a systems perspective— understanding all the influences on blood-sugar control, insulin, and our mitochondrial function (nutritional balance, hormone balance, inflammation, toxins, energy production, oxidative stress, and psychological stress—or the seven keys to UltraWellness, which lead to an UltraMind)—we can create a lifestyle and program that works to keep us healthy, happy, alert, mentally sharp, thin, and more likely to live to 120.
Finding the Gene Control Switch for Mitochondria
At a conference on longevity and aging I had a chance to have a conversation with Dr. Leonard Guarente from the Massachusetts Institute of Technology, who in 1995 discovered a gene called SIR-2 in yeast that controlled longevity. David Sinclair, who authored one of the studies above, was his student.
The SIRT-1 gene (which is what it is called in humans) or sirtuin family of genes works by protecting and improving the health of your mitochondria.24 I asked him how this master gene controlled longevity, the gene through which the effects of this grape compound, resveratrol, did its magic.
His answer was quite simple really. Sugar! This gene is the master-control switch for healthy aging because it improves blood-sugar balance and insulin sensitivity through its effects on mitochondria.
When your mitochondria are running in top shape, you can metabolize or process all your calories and produce energy. But when they are overloaded with too many empty calories, they are unable to keep up, and too many free radicals are generated, slowing down your cells and your metabolism. By increasing the activity of this master gene, you improve the overall function of your mitochondria, improve blood-sugar control and insulin sensitivity, and boost your antioxidant defenses. You live longer, and your brain works better.
This is no surprise, since all of the signs of aging such as hardening of the arteries and organ damage (especially brain damage) are increased through worsening blood- sugar control—even before you get diabetes. Diabetics, in fact, have smaller and more poorly functioning mitochondria and get cancer, heart disease, depression, and dementia at far greater rates than the general population.25
Remarkable new research links mood disorders to problems with insulin and blood-sugar control. In fact, some researchers suggest calling depression “metabolic syndrome type II,” meaning that the changes in the brain from oxidative stress, inflammation, and mitochondrial injury lead to altered mood.26
So if we could fix our blood-sugar control and boost our mitochondria, we could live longer and disease-free.
Taking a big-picture view, we don’t just want to take a magic pill that will be unlikely to work given all the other real life insults affecting us, such as poor diet, stress, environmental toxins, and sedentary lifestyle.
This just takes us back to the basic principles of systems biology and Functional Medicine at the foundation of The UltraMind Solution.
One of the keys to this program is to rebalance your diet by eating real, whole foods instead of the highly processed, high-calorie, high-fat diets that cause imbalance in your blood sugar and produce catastrophic effects on your mitochondria.
Or you could drink 1, 500 bottles of red wine a day.
But what else can you do to boost your mitochondrial function and prevent the destruction of your brain?
Taking supplements to enhance your mitochondrial performance is actually a well-founded scientific approach to overcoming oxidative stress. It’s simply that taking huge quantities of resveratrolalone (or as some magic pill) without changing your lifestyle or using all the other nutrients needed for optimal mitochondrial function is a misguided approach. This is especially true considering the fact that resveratrol really has an impact on your insulin/sugar balance, which is more effectively treated with diet, exercise, and lifestyle changes anyway.
Many vitamins and minerals and “conditionally essential” nutrients are known to control energy production and to protect and defend your mitochondria. These “antiaging” or neuroprotective supplements work because of the way they help protect and optimize mitochondrial function, both directly and indirectly.
In 1997, the first scientific paper on resveratrol was published showing that this polyphenol could prevent cancer in experimental models.1
Since then, researchers have documented resveratrol’s ability to favorably modulate multiple processes associated with degenerative disease, fromatherosclerosis to obesity.
In 2011, the findings of the 2010 Resveratrol Conference2 held in Denmark were published. Its primary objective was to examine the totality of the evidence for resveratrol’s disease-preventing role in aging humans. Nearly 3,700 published studies were analyzed.
In numerous studies—including those at BioMarker Pharmaceuticals, a Life Extension-sponsored research institution—resveratrol has demonstrated effects that mimic those of caloric restriction, the best-documented anti-aging strategy to date.
To date, the most reliable, best-researched way to extend life span is through the practice of caloric restriction, which involves reducing calorie intake while simultaneously maintaining good nutritional status.
In numerous studies, restricting calorie intake in laboratory animals has been shown to prolong their life span by as much as 60%.1-3 While scientists have not yet determined whether caloric restriction extends life span in humans, the preliminary evidence is very promising. In humans, consuming a low-calorie diet is associated with several possible markers of greater longevity, such as lower insulin levels and reduced body temperatures, along with less of the chromosomal damage that typically accompanies aging.4 Furthermore, people who consume a low-calorie diet may be less prone to diseases associated with being overweight or obese, such as metabolic syndrome, diabetes, cancer, and atherosclerosis.
This heightened interest in resveratrol has produced several recent breakthroughs. In a landmark study, Harvard University scientists showed that resveratrol could prolong survival by regulating a gene associated with aging that is present in all life forms.5 They demonstrated that while middle-aged mice fed a high-calorie diet suffered the ravages of obesity—including metabolic changes resembling diabetes, liver and heart damage, and premature death—mice that were fed resveratrol in addition to the high-calorie diet actually exhibited beneficial changes in their physiology, resembling those of mice fed a standard diet.5
Among the life-prolonging benefits of resveratrol supplementation demonstrated in the study were:
- increased insulin sensitivity
- lower blood sugar
- enhanced mitochondrial energy production
- improved motor function.
- While mice on the non-supplemented high-calorie diet developed enlarged, fatty livers, resveratrol supplementation prevented these changes. Similarly, heart disease and evidence of atherosclerosis were seen in mice fed the high-calorie diet, but not in those that were also given resveratrol. Resveratrol significantly increased survival, reducing the risk of death from the high-calorie diet by 31%. Together, these findings offer powerful evidence that resveratrol protected the animals from the harmful effects of a high-calorie diet.5
the Harvard scientists concluded. “The ability of resveratrol to prevent the deleterious effects of excess caloric intake and modulate known longevity pathways suggests that resveratrol and molecules with similar properties might be valuable tools in the search for key regulators of energy balance, health, and longevity.”5
Current evidence suggests that resveratrol exerts antioxidant effects, boosts energy production, and favorably alters patterns of gene expression.
Resveratrol also helps preserve levels of glutathione, one of the body’s most essential antioxidants.6
Resveratrol stimulates energy production in the cellular powerhouses known as the mitochondria. Diminished mitochondrial energy production is associated with reduced longevity. By enhancing the production of life-sustaining energy, resveratrol may help protect against metabolic disease and obesity, thereby improving health and prolonging survival in animals.7
Some of the genetic pathways influenced by resveratrol are similarly affected by caloric restriction. For example, caloric restriction is associated with long-term activation of AMP-activated kinase (AMPK), a metabolic enzyme promoting insulin sensitivity and fatty-acid oxidation. Resveratrol likewise increases AMPK activity, which is associated with life-span extension.5
Scientists believe that caloric restriction increases life span in part through its effects on the sirtuin genes.5 Present in all life forms, sirtuin genes are associated with aging and longevity. Resveratrol may confer benefits similar to those of caloric restriction by influencing the sirtuin gene known as SIRT2.5,8-10 In the Harvard study, resveratrol helped counteract changes in SIRT2 expression induced by a high-calorie diet.5
“The genes and pathways [affected by resveratrol or by caloric restriction] are related to activation of sirtuins, a class of histone deacetylase enzymes (HDACs) involved in cell death and life-span regulation,”
- In a recent Harvard study, mice that consumed a high-calorie diet known to shorten life lived longer when they also consumed resveratrol. These mice also had better coordination, less heart and liver damage, and better insulin sensitivity than overweight mice that were not fed resveratrol.
- Scientists have proposed that resveratrol in red wine may help explain the “French paradox”—the fact that cardiovascular disease rates in France are relatively low, despite a diet traditionally high in fat. Because widespread use of pesticides has diminished the amount of resveratrol contained in grapes and red wine, supplemental resveratrol may the best way to ensure optimal intake.
- Resveratrol may enhance health and support longevity via several mechanisms. These include its potent antioxidant effects, ability to enhance cellular energy production, and ability to influence patterns of gene expression in a manner similar to caloric restriction (the best-documented method of extending life span in animals).
Resveratrol may inhibit platelets from clumping together, thus reducing the risk of deadly blood clots that can lead to heart attack and stroke.18-21
OES RESVERATROL EXPLAIN THE “FRENCH PARADOX”?
|Although French cuisine is world renowned for its rich sauces, gourmet cheeses, and fine wines, the French enjoy a relatively low incidence of coronary heart disease.12,13 This apparent anomaly has led scientists to wonder what dietary or lifestyle factors might account for the so-called “French paradox.” Studies suggest that resveratrol, a constituent of red wine, may help protect the French from the adverse health effects of their traditionally rich diet, while also protecting the liver against the toxic effects of alcohol.14|
Technically, resveratrol is a chemical known as trans-3,5,4’-trihydroxystilbene. Produced by grapes, berries, peanuts, and certain other plants in response to stressful conditions, resveratrol and related biochemicals known as phytoalexins function as natural antibiotics, protecting plants against attack by pathogens.15
Life Extension recently discussed the French paradox with Milos Sovak, MD, founder of Biophysica, Inc., a California-based biomedical and pharmaceutical research company. According to Dr. Sovak, the hearty wines of southern France, produced from the Vitis vinifera vine, used to produce up to 30 mg of resveratrol per liter. This is no longer the case.
“The French who consumed up to 1 liter/day of wines originating in the South have had convincingly fewer cardiovascular afflictions than their brethren to the North,” says Dr. Sovak. “That situation is rapidly changing. With the advent of pesticides, plants are now producing almost no phytoalexins and it is rare today to find more than 2-3 mg of resveratrol per liter. That alone should be sufficient reason for supplementation with this compound regardless of the many studies—some reliable, some not—that show various advantages to red wine.”
Based on his study of experimental life-span extension in mice,45 Dr. Richard A. Miller of the University of Michigan suggests that resveratrol may extend the human life span.
Dr. Miller speculates that with effects similar to those of caloric restriction, resveratrol could extend human longevity to about 112 or even 140 years of healthy life.
The participating scientists at the 2010 conference covered a broad range of research on the biological effects of resveratrol. Since 1997, roughly 3,650 studies on resveratrol have been published, all of which were reviewed.
Based on the most encouraging data, they focused specifically on resveratrol’s capacity to favorably modulate factors involved in five of the leading causes of death in maturing Americans: cancer, heart disease, neurodegeneration, systemic inflammation, obesity, and diabetes.1,2
A new study shows that high doses of resveratrol may improve brain blood flow and could potentially boost brain health.
Much of the well-deserved fanfare surrounding resveratrol has centered on its role in enhancing longevity, but new research is expanding this focus and showing this potent antioxidant may influence many aspects of your health, including that of your brain.
Resveratrol is unique among antioxidants because it can cross the blood-brain barrier to help protect your brain and nervous system. This latest study by researchers from the Brain, Performance and Nutrition Research Centre at Northumbria University is the first to show that resveratrol has a marked impact on increasing blood flow to your brain.
After taking either 250 or 500 milligrams of resveratrol, study participants experienced a dose-dependent increase in cerebral blood flow, which suggests that resveratrol may play a role in keeping your brain function healthy.
The fact that a nutrient can readily improve the flow of blood around your brain is a significant finding that is reflective of a major benefit to human health. The researchers used either a 250 mg or 500 mg dose, with the higher dose showing even further enhanced oxygenation.
It’s a polyphenolic bioflavanoid antioxidant that certain plants produce in response to stress, such as injury or fungal infection. It first entered the limelight as a potential explanation for the so-called French paradox — the tendency for French people to have great cardiovascular health despite a “poor” diet and love for wine (which is a rich source of resveratrol).
It later made headlines in 2003, when Harvard researchers found it could extend the lifespan of yeast cells. Since then it has been found to similarly extend the lifespan of nematode worms, fruit flies, fish, and mice. It works by activating a gene called sirtuin1, which is also activated during calorie restriction — another method to extend lifespan — in various species.
Resveratrol also seems to produce many similar benefits as exercise, including lowering insulin levels, which is a key to fighting disease and staying young. Insulin resistances speed up the aging process, while keeping insulin level resistance normal has the opposite effect.
More than half a million Americans die of cancer each year, despite considerable strides in our understanding of the disease.18 The very first scientific study of resveratrol showed a preventive effect on skin cancer,1 and since that time more than 1,100 papers have been published on the subject of cancers in general.2
Once initiated, cancers grow by proliferation of abnormal cells. Resveratrol is a modest anti-proliferative agent, as new data show. Consumption of resveratrol by human colon cancer patients reduced tumor cell proliferation by 5% at a dose of 500 to 1,000 mg daily for only 8 days prior to surgery.22
The body naturally controls cancer growth through the process of apoptosis, by which cancer cells are triggered to die off. Proper apoptosis requires activation of important “suicide” genes found in all cancer cells. Resveratrol has recently been found to increase expression and activation of one important “suicide” pathway known as p53.24
TABLE 1: RESVERATROL’S 12 KEY ANTI-AGING MECHANISMS2
|Mechanism||Diseases or |
|All chronic disease|
|All chronic disease|
|Resveratrol targets 12 key mechanisms to combat chronic, age-related diseases, including those that comprise the primary contributing factors to the leading causes of death.|
All of this means resveratrol is reaching the level of large-scale clinical trials by mainstream physicians. Phase I, “dose-finding” studies have now been completed that validate resveratrol’s safety even at very high levels of up to 5 grams (this does not mean people should take this high dose yet).25,34
TABLE 2: SUFFICIENT EVIDENCE EXISTS FOR RESVERATROL’S
|Heart disease||Reduces incidence of hypertension,|
heart failure, ischemia (loss of blood flow)
|Stroke||Reduces incidence of hypertension,|
(e.g., Alzheimer’s, Parkinson’s), brain injury
|Diabetes (and obesity)||Improves insulin sensitivity, reduces blood glucose levels, reduces high-fat diet-induced obesity and visceral (abdominal) fat|
|Resveratrol targets 12 key mechanisms to combat chronic age-related diseases, including those that comprise the primary contributing factors to the leading causes of death.|
New science reveals in great detail how resveratrol acts through activation of the “longevity gene” SIRT-1, which triggers many favorable events that may help prevent Alzheimer’s and other neurodegenerative diseases.35,46-48
Much of resveratrol’s neuroprotection arises from its ability to interfere in the cascade of events caused by accumulation of abnormal proteins known as amyloid-beta.49Amyloid-beta triggers oxidative stress and inflammation that directly damages brain cells, especially in memory centers of the brain. That’s why Alzheimer’s patients have such profound and progressive memory loss.
Resveratrol inhibits amyloid-beta toxicity at multiple points in the cascade.49 Resveratrol acts as a powerful antioxidant, scavenging oxygen free radicals and inducing protective enzymes such as heme oxygenase.36,50
An intriguing study published in late 2010 demonstrated that, by protecting brain mitochondria, the combination of resveratrol and mitochondria-targeted antioxidants could restore normal function in an experimental model of Alzheimer’s.55 That effect in turn produced new outgrowth of the tiny intercellular connections known as neurites, which are damaged or lost in Alzheimer’s and other neurodegenerative diseases.55
Finally, an important recent study showed that orally administered resveratrol achieves effective concentrations in brain tissue, meaning it crosses the blood-brain barrier that keeps so many other potentially beneficial compounds out.
High blood sugar, both chronically and acutely following a meal, exerts massive oxidative stress on body proteins, ultimately changing their structure and inducing inflammation. It’s these changes that produce diabetic complications. New studies show that resveratrol, by activating the important SIRT-1 system, inhibits cellular oxidative stress and resulting inflammation in diabetes.58,59
Resveratrol improves insulin sensitivity through its effects on SIRT-1.58,60 New, highly detailed data reveal that these benefits arise from resveratrol’s ability to stimulate metabolic sensing pathways in cells that allow them to use insulin and glucose more effectively, helping to reduce blood sugar levels.61
Glucose-damaged blood vessels lose their ability to regulate blood flow in brain and heart tissue, contributing to heart attack and stroke damage. Chronic resveratrol treatment has recently been found to restore blood vessel responsiveness in diabetic animals.40
Studies released since that time further clarify and amplify the power of resveratrol to prevent, and in some cases reverse, the biological changes associated with chronic disease and aging. Compelling evidence is now available for resveratrol’s ability to favorably modulate factors implicated in the onset of heart disease, cancer, stroke, Alzheimer’s disease, and diabetes.
The resveratrol mice also experienced less degradation in their nerve tissues compared to other mice, which helped them effectively thwart many of the negative effects of aging.
Conducted by Jane Cavanaugh, an assistant professor of pharmacology at Duquesne University in Pittsburgh, Pennsylvania, and her colleague, the study found that laboratory mice taking resveratrol experienced less neural cell death than other mice, indicating that resveratrol somehow blocks the cell death that is normally induced by the neurotransmitter dopamine as a result of stress. Taking resveratrol, in other words, has the potential to block stress-induced aging, as well as protect nerve cells from being damaged or killed.
Although resveratrol occurs naturally in grapes, nuts and other fruits, most resveratrol on the market is extracted from an herb called Polygonum cuspidatum. We agree that the resveratrol from Polygonum cuspidatum is just like that of grapes and other sources of resveratrol. Unfortunately, Polygonum cuspidatum is known to be a toxic herb when consumed over time by humans. In Asia, Polygonum cuspidatum is used as a medicinal herb for snake bites. So it is not meant to be consumed for a prolonged period of time, and certainly not for a lifetime. Polygonum cuspidatum is NOT a tonic herb.
Unfortunately, most dietary supplement companies do not FULLY extract the resveratrol from the Polygonum cuspidatumraw material. They leave half of their extracted powder as a Polygonum cuspidatum extract. In other words, look at the label of other resveratrol products and you will find that many of them are 50% or 25% extracts – which means that half or three quarters of the material is actually Polygonum cuspidatum extract. That is unfortunate.
Dragon Herbs extracts virtually ALL of the resveratrol out of the Polygonum cuspidatum and leaves virtually no trace of the Polygonum cuspidatum in the PureTrans Resveratrol powder. Dragon Herbs PureTrans™ Resveratrol contains NO Polygonum cuspidatum. That makes a BIG DIFFERENCE.
Resveratrol is meant to be consumed as a dietary supplement, not as a toxic herb. It should be taken over a lifetime as a tonic. It is simply not good to take someplace between 30 mg and 400 mg of Polygonum cuspidatum every day. If you are taking a brand of resveratrol that uses resveratrol that is 50% Polygonum cuspidatum, then you are taking the same amount of Polygonum cuspidatum extract as you are resveratrol every day. That is not good.
animal studies have shown that resveratrol increases mitochondrial density and function.
Mitochondria are located in animal and human cells and convert food into adenosine triphosphate (ATP), the energy currency for cellular metabolism and the energy source for organs or muscles comprised of those living cells.
The researchers induced mini-strokes in rats to cause temporary oxygen and blood reduction in their mid-brains. Shortly before and two hours after each induced stroke, one group was administered 10(-7) grams per kilogram of resveratrol while the control group was not treated with resveratrol.
They found the treated group had their mitochondrial glutathione restored rapidly with minimal mitochondrial damage and brain edema (swelling) compared to the control group without resveratrol.
Cavanaugh’s assistant Erika Allen, a graduate student, fed both young and old mice a diet containing resveratrol for eight weeks. She also compared each mouse’s ability, both before and after the resveratrol regimen, to cross a steel mesh balance beam, reportedly documenting and analyzing each stumble or misstep along the way.
By the fourth week, she and Cavanaugh began observing that older mice who had trouble crossing the balance beam at the start of the study were experiencing dramatic improvements as a result of taking resveratrol. These older mice, in fact, were already effectively able to keep up with the younger mice a mere halfway into the study, a remarkable observation.
In another amazing study recently published in the journal Nutrition Research, researchers out of India found that resveratrol also helps fight and even cure type-2 diabetes by normalizing hemoglobin levels in the blood. Compared to diabetics receiving only oral hypoglycemic drugs, diabetics taking 250 milligrams (mg) daily of a specific brand of resveratrol for three months experienced dramatically improved blood sugar levels.
These same trial patients reportedly experienced both lowered blood pressure levels and improved blood cholesterol levels as a result of taking resveratrol,
Under laboratory conditions, the researchers examined the mechanics of how Mediterranean diets with high levels of resveratrol manage to reduce cardiovascular diseases.
They discovered that resveratrol scavenged H2O2 (hydrogen peroxide) and prevented premature, stress-induced cell death among the surfaces of artery inner-walls.
Resveratrol has beenshowninawealthof studies tobeapowerful
chemoprotectorant and chemotherapeutic agent against breast cancer
By late 2010, there were over 4,000 published studies on resveratrol and a remarkable consensus was developing.
Resveratrol was first isolated
from a plant source in 1940 in the West, but has been used as a traditional medicine in Asia for more than 2,000 years.
In September 2010 the firstinternational conference of resveratrol researcherswas held about a one-hour train ride outside of Copenhagen,
Denmark. At this milestone event, over 120 of the world’s leading scientists from prestigious research institutions in the US, Asia, India,
Europe andAustraliamettopresenttheir findingsonresveratrol.After
attending this conference and listening to the presentations of these
distinguished and highly accomplished scientists, I am now convinced
that, if anything, my comparison of resveratrol with penicillin was extremely conservative.
New and surprising revelations are being announced almost weekly nowbytheleadinguniversities,medical schoolsandresearchorganizationsaroundtheworld
No single molecule or drug known to medical science has shown the
wide range of potential preventative, therapeutic, and quality of life
enhancement properties of resveratrol. It has been shown to inhibit
cancer, kill bacteria, viruses and fungal infections, extend life span in
animals, improve energy production in cells, quench damaging free
radicals, increase glucose tolerance in diabetics, improve cardiac function, enhance physical and mental fitness and concentration, repair
damaged DNA, prevent cell damage from nuclear radiation, and much
A 2003 study at Harvard University found that resveratrol mimics the effects of caloric restriction in yeast cells, boosting their life spans by as much as 70%.3 The following year the researchers went on to demonstrate that resveratrol slows aging in two standard laboratory animals, roundworms and fruit flies.4 That made resveratrol the first compound to show anti-aging effects in widely divergent species. Then in 2006, scientists in Pisa, Italy, showed that resveratrol’s magic could be applied to more advanced animals— large doses of resveratrol extended the life span by more than 50% in a species of fish, Nothobranchius furzeri, which typically lives just nine weeks.5
Mitochondria are the power plants of cells, which are responsible for intracellular energy production. Resveratrol activated a protein in the sirtuin family (SIRT1), which then stimulated the activity of another protein involved in mitochondrial function. Other recent studies, including one conducted at the Joslin Diabetes Center, have found another member of the sirtuin family of cellular proteins that may play a major role in how fat is produced and stored, offering a new target for treatments to prevent obesity and reduce the risk of type 2 diabetes.7,8
The French researchers surmised that resveratrol helped control weight gain by enhancing energy expenditure.6Since the study found a link between sirtuins and energy utilization, the researchers concluded that resveratrol may be helpful in the prevention and treatment of certain metabolic disorders, especially those related to mitochondrial dysfunction, such as Alzheimer’s and Parkinson’s disease—two neurodegenerative conditions that become more prevalent with aging.9
In a landmark mouse study published in the journal Nature, resveratrol countered some effects of a high-calorie diet, improving the health of the mice and increasing their life span, even though they did not lose any weight.32These mice shared many of the problems of humans on an equivalent diet, including obesity, insulin resistance, and heart disease.
The study compared middle-aged mice fed a standard diet with those on a high-fat (60% of daily calories) diet, with and without high-dose resveratrol supplements. Over a two-year period, the resveratrol-fed mice on the high-fat diet lived as long as the ones on a standard diet and at least 15% longer than their untreated, obese peers.
Additionally, the resveratrol-treated animals displayed greater numbers of liver mitochondria than animals who consumed a high-fat diet that did not contain resveratrol.
Perhaps the most intriguing result of the recent mouse studies was resveratrol’s ability to increase the number of mitochondria, the key cell components that serve as energy producers.6,32
Resveratrol’s effect on mitochondria may be enough by itself to account for much of the compound’s demonstrable effects in the mouse studies. It may account for the enhanced running abilities observed in the overweight mice treated with resveratrol. What makes the findings of these recent mouse studies so potentially significant to researchers is that humans have genes similar to those linked to resveratrol intake in the mice.6,32
When added to cells cultured in media, resveratrol has been found to inhibit the proliferation of a variety of human cancer cell lines, including those from breast, prostate, stomach, colon, pancreatic, and thyroid cancers.33
An earlier study published in the Journal of Carcinogenesis found that dietary resveratrol helped prevent breast cancer in female rats. Starting at birth, rats were fed either a control diet or a diet supplemented with resveratrol. At the age of 50 days, both groups were exposed to a cancer-inducing chemical. The resveratrol-fed rats were significantly protected against breast cancer, demonstrating fewer tumors per animal and longer tumor latency (an asymptomatic period in this disease process). The researchers concluded, “our work supports the previous reports that resveratrol in the diet is effective at inhibiting…mammary cancer.
In 1929, scientists at Cornell University first discovered the life-extending effects of caloric restriction in fish. They later found that caloric restriction extended maximum life span in rats. Calorie restriction is the only scientifically established way to slow aging in mammals. The Cornell researchers found that reducing normal caloric intake by up to 50% extended the mean and maximum life span in rats.5,60,61Subsequent studies have shown that consuming fewer calories, while simultaneously taking adequate vitamins and other nutrients, can increase the life span of everything from yeast, worms, and fruit flies to mice, rats, and dogs by up to 40%.62,63
This is exactly what we’re trying to achieve with The Superman Diet: we need to minimize our caloric intake, while maximizing the nutritional density we get from the foods we eat, for the purpose of achieving a longer higher quality life.
Scientists were eager to determine if caloric restriction might similarly promote longevity-associated changes in human subjects. In 2006, researchers at Washington University in St. Louis reported that 25 volunteers (average age 53) who had been practicing caloric restriction for 3-15 years had cardiovascular systems that were much healthier than matched control subjects eating standard Western diets.64
The study participants demonstrated diastolic heart muscle function that was significantly better than the Western-diet group and similar to that displayed by younger individuals. Study volunteers ate as little as 1,670 calories a day, rather than the 2,445 or more calories in a typical adult’s diet. The study documented that caloric restriction has a beneficial effect on heart function by lowering systolic blood pressure and decreasing systemic inflammation and myocardial fibrosis.64 Since cardiovascular disease is so prevalent in aging adults, the finding that caloric restriction promotes a more youthful cardiovascular profile is highly important.
Longevity scientists continued to seek out the ways in which caloric restriction might stop or even turn back the clock in humans. In 2006, researchers announced the results of a six-month study of the effects of a calorie-restriction diet in humans. In the study, a group of adults cut back their food intake to as little as 890 calories a day, and maintained the diet for six months. The researchers discovered that two key biomarkers of longevity (fasting insulin level and body temperature) decreased after prolonged calorie restriction.65
These exciting findings led to a flurry of research on the health benefits of caloric restriction. In a systematic review of these findings published in JAMA, American and Italian researchers concluded, “calorie restriction in adult men and women causes beneficial metabolic, hormonal, and functional changes…”66
ENGINEERING BIOLOGICAL IMMORTALITY
|When we discuss the ability of nutrients like resveratrol, drugs like metformin, and experimental regimens such as caloric restriction to induce favorable changes in gene expression in experimental animals, most people do not realize the ultimate objective of this type of research.|
While the DNA in the nucleus of our cells includes thousands of genes, it appears that relatively few of these genes control functions that are critical to optimal health and longevity.
As mammals (including humans) age, beneficial genes are “turned down,” whereas genes that are detrimental to cellular function are “turned up.” Some genes may be turned off and on with advancing age, and others may have positive influences in youth, but negative influences as we grow older.
Examples of beneficial genes that are “turned down” during normal aging are genes that:
Examples of detrimental genes that are “turned up” during normal aging include those that:
By causing the genes involved in aging to function as they did in youth, it may become possible in the future to reprogram our genes to keep us alive in a state of perpetual youth, which could lead to biological immortality.
Just consider: although caloric restriction was discovered to extend maximum life span in mammals in the 1930s, only recently have scientists begun to identify the molecular mechanisms that may explain the benefits of caloric restriction, as well as potential caloric-restriction mimetics such as resveratrol
“We were able to confirm that under normal living conditions, resveratrol lengthened lifespan in honey bees.”
In an effort to uncover the mechanisms involved in resveratrol’s benefits, the researchers examined the compound’s effect on appetite. In comparison with bees that did not receive resveratrol, those given the compound had less interest in consuming sugar solutions unless the sugar was highly concentrated. “Because what we eat is such an important contributor to our physical health, we looked at the bees’ sensitivity to sugar and their willingness to consume it,” Dr Rascón explained. “Bees typically gorge on sugar and while it’s the best thing for them, we know that eating too much is not necessarily a good thing.”
Further experimentation revealed that resveratrol reduced food consumption in bees allowed to eat as much as they liked of diets containing carbohydrate and protein. “Surprisingly, the bees that received the drug decreased their food intake,” Dr Rascón reported. “The bees were allowed to eat as much as they pleased and were certainly not starving–they simply would not gorge on the food that we know they like. It’s possible resveratrol may be working by some mechanism that is related to caloric restriction – a dietary regimen long known to extend lifespan in diverse organisms.”