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How the world got lost on
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November 1, 2011: by Bill Sardi
Las Vegas, NV (Nov 1, 2011) – For the first time the red wine molecule resveratrol has busted out of the confines of the animal laboratory and into the human arena where researchers report striking results.
The bottom line: for those individuals who exercise regularly and count calories, add a red wine pill to your daily regimen. For those sedentary Americans who overeat, a resveratrol (rez-vair-ah-troll) pill may actually supplant gym workouts and deprivation diets. That’s the latest news issued by European researchers in an online report published in the journal Cell Metabolism, as reported by ABC News.
The large cloud of scientific doubt over whether resveratrol actually targets a survival gene and serves as molecular mimic of a limited-calorie diet was lifted today as researchers report a modest dose of this red wine molecule mimics a calorie-restricted diet and/or endurance training in humans. Prior studies in laboratory mice were either inconclusive or disappointing.
Researchers say the difference between prior studies involving laboratory mice and humans might be explained by the discovery that humans metabolize resveratrol at a different rate than rodents. While the dose of resveratrol used in this human study was ~200-fold lower than those used in prior studies involving laboratory mice, similar blood plasma levels were achieved. Gone is the false notion that one-thousand bottles of red wine need to be consumed to reproduce the beneficial effects seen in the laboratory.
A daily dose of 150 milligrams of resveratrol employed in this study of healthy but overweight adults, while far greater than what can be obtained from drinking 3-5 glasses of the best aged dark red wine (~3.5 mg), is far less than the 1565 milligram human equivalent mega-dose used in a mouse study published in 2006 which failed to demonstrate life-extension. Lower doses may be the key here. Prior studies in laboratory mice showed relatively low doses of resveratrol partially mimic the effects of calorie restriction. This means health and longevity seekers can obtain resveratrol in the dose employed in this study from dietary supplements at affordable prices.
While the measured results were modest, with a few striking results such as systolic blood pressure declined by 5 points (from ~130 to ~124), the effects are expected to increase with more prolonged use. The study only measured the effects of supplemental resveratrol over a 30-day period.
In prior experiments in mice, short-term calorie restriction (12-weeks) activated 198 genes, resveratrol 225 genes, while long-term calorie restriction significantly altered 831 genes. So the genomic effects appear to expand with continued use over time.
In this human experiment, resveratrol was found to significantly alter gene expression (protein making) in 469 genes, the first time such a measurement has been reported in humans. Recently other researchers reported that only 295 out of the library of 25,000 human genes have been identified as longevity genes. This means the life extending benefits of a calorie restricted diet are within reach without having to deprive oneself of food.
The broad array of genes influenced by resveratrol speaks loudly for its promise to overcome the dietary sins and sedentary lifestyles of modern man. Single-gene targeted drugs have produced abysmally limited results in the treatment of disease. But in this instance resveratrol poses to turn biology and pharmacology upside down. Instead of a single synthetically-created drug molecule targeting a single gene or cell receptor site in the treatment of a single disease, which is how most modern drugs operate today, resveratrol represents a single natural molecule that can address many gene targets and all the chronic diseases of aging in one pill.
While forced limited-calorie diets have been shown produce favorable health parameters and double the lifespan of laboratory animals, they are not expected to be practical or achievable for human populations where food is abundant. Even the exceptional longevity noted among the people living in the Japanese prefecture of Okinawa was produced by relative scarcity of food. With greater abundance of food the so-called “Okinawa effect” is beginning to disappear.
There were no side effects reported among the eleven middle-aged healthy overweight males who participated in the study. However, there is no mention in the report whether any of these subjects were taking prescription drugs at the time. Since resveratrol inhibits detoxification enzymes in the liver it should not be consumed as the same time as prescription medications. There was no meaningful difference in body weight or body mass, similar to what has been reported in animals.
A pure (99%) pure synthetically-produced form of resveratrol was used in the study but similar results are expected from comparable doses of resveratrol extracted from botanical sources.
In this study resveratrol was found to indirectly activate the Sirtuin1 gene (akin to the SIR2 gene in lower life forms) in human tissues via AMPK (adenosine monophosphate kinase), an enzyme that serves as a master metabolic regulator. Prior studies cast doubt on Sirtuin1 as the direct gene target of resveratrol and led many to falsely believe resveratrol is of no value biologically in regard to mimicry of a calorie-restricted diet.
Resveratrol also appeared to favorably affect the efficiency of small organelles called mitochondria in living cells to produce cell energy. The mitochondria are the atomic power plants of living cells. Only about 4% of mitochondria are functional by age 80. Thirty-day use of resveratrol did not seem to improve the number of mitochondria.
Some researchers warn consumers they should not assume higher doses of resveratrol will be safe or more efficacious. Low-dose resveratrol has been found to mimic calorie restriction and mega-doses may turn resveratrol from an antioxidant to a promoter of oxidation. There are many mega-dose resveratrol dietary supplements on the market today that pose a potential risk and may not offer the benefits described in this recent study.
A 5000-milligram dose of resveratrol was found to rapidly induce kidney failure among humans with a form of bone marrow cancer (multiple myeloma). One exception may be a particular brand of resveratrol pills (Longevinex®) which was demonstrated in an animal study to be non-toxic to living cells even at very high doses.
An often overlooked aspect of resveratrol is that it is known to activate hormesis, that is, it works as a low-dose toxin that activates the body’s defenses. There should be no surprise that high doses are counterproductive. Near starvation also induces hormesis (aka calorie restriction). Low-dose resveratrol activates a transient gas in the blood circulation called nitric oxide which widens (dilates) blood vessels and improves circulation and also activates synthesis of two other molecules, adenosine and heme oxygenase, which protect the heart, brain and other tissues in the event of a heart attack. This has been called the best method of heart protection.
Some researchers believe the favorable biological effects achieved in this study can be further enhanced by accompaniment of other molecules found in red wine. Animal studies confirm synergistic effects when resveratrol is combined with other similar molecules.
Professor Roger Corder of the William Harvey Research Institute in England says the combination of molecules provided in red wine is responsible for its low-dose effect and the unprecedented longevity seen among French red wine drinkers.
Some resveratrol pills commercially available today incorporate any array of other red wine molecules into their products. One such brand, Longevinex® (pronounced long-jev-in-ex), was found to activate 9-fold more genes than plain resveratrol in laboratory mice over the short-term and in a relatively short period of time activated twice as many genes as life-long calorie restriction.
In a rodent experiment of intentionally-induced heart attack, both low-dose plain resveratrol and Longevinex® returned gene activation as measured by microRNA to pre-heart attack profiles with Longevinex® exhibiting a more demonstrable effect, reducing the scarred area of the heart 28% better and the pumping pressure of the heart 100% better than plain resveratrol. Mega-doses of plain resveratrol increased scarring of rodent heart tissue following a heart attack while mega-dose Longevinex® did not.
Longevinex® has consistently been shown to work in a superior manner to plain resveratrol at a lower dose. One Longevinex® capsule provides 100 milligrams of micronized/ microencapsulated trans resveratrol in a vege-capsule, two-thirds of the dose employed in this most recent human study.
There is promise that resveratrol may be employed in place of aspirin to prevent heart attacks particularly because baby aspirin tablets (81 mg) are not effective in reducing blood clots that form in coronary arteries and a standard dose aspirin tablet (325 mg) induce sometimes lethal bleeding gastric ulcers. Though some researchers lament that, after years of research, not one human trial involving resveratrol has commenced for heart disease.
According to the Natural Medicine Comprehensive Database, there are 345 brands of resveratrol pills, most which provide ineffective or potentially problematic doses and are untested in animal or human trials. Longevinex® is currently the best-tested resveratrol-based dietary supplement.
Effect On Humans: 150 mg Resveratrol/Day 30 Days-11 Adult Males
|Blood Plasma Data (selected)|
(0.5 or less is significant)
|Blood glucose (mmol/l)||5.28||5.06||0.050|
|Tumor necrosis factor (pg/ml –inflammation)||16.15||15.14||0.040|
|C-reactive protein (ng/ml inflammation)||1.52||1.33||0.110|
|Measured Clinical Improvement|
|Systolic blood pressure (mmHg)||130.5||124.7||0.006|
|Diastolic blood pressure (mmHg)||81.6||80.0||0.018|
|Mean arterial pressure (mmHg)||97.9||94.9||0.020|
|Source: Cell Metabolism, online 2011|