Life Extension Magazine February 2008
Living Longer, Healthier Lives with Resveratrol
By David Nayor and Dale Kiefer
Resveratrol Protects Heart Muscle
A study on rat heart cells suggested resveratrol could benefit heart tissue by limiting the effects of cardiac fibrosis (hardening or stiffening of the heart tissue). In the study, researchers prevented the actions of a hormone called angiotensin II by treating rat cardiac fibroblast cells with resveratrol. Angiotensin II is produced at high levels during heart failure and episodes of hypertension. Unfortunately, angiotensin II causes cardiac fibroblast production to go into overdrive, prompting these cells to produce excessive amounts of collagen tissues, which leads to a stiffening of heart muscle.41 Researchers pretreated rat cardiac fibroblasts with resveratrol prior to adding angiotensin II. Resveratrol stopped angiotensin II’s ability to promote the growth and spread of cardiac fibroblasts. Most importantly, resveratrol prevented these cells from turning into myofibroblasts, a specialized type of fibroblast that produces large quantities of collagen.41,42
The resveratrol used in dietary supplements provides differing blends of free resveratrol and resveratrol glycosides (resveratrol bound to sugar), making it difficult to establish reliable assay methods.
As an example of the inconsistencies that can occur when assaying finished resveratrol products, Life Extension recently sent all of its resveratrol-containing supplements out to four different independent analytical labs. The tallied results from all four independent laboratories confirmed that all products exceeded label claims for resveratrol potency. Every lab, however, showed differing levels of resveratrol. The chart below shows the amount of resveratrol found in each Life Extension resveratrol supplement:
As you can see, the variation in resveratrol assay results is minimal in some products, while other products show a greater disparity. These kinds of problems are known to occur when measuring a complex compound like resveratrol in a finished botanical product. An example of dissimilar results can be seen in the Whole Grape Extract, which the assay from Lab A showed contained a low of 21.49 mg of resveratrol, whereas the assay from Lab C came out with a high reading of 36 mg. The average finding of all four analytical labs is 27.85 mg per capsule, which is slightly above label claim.
This variability in resveratrol assay results also occurred in the Dual Action Cruciferous Vegetable Extract formula. For this complex product, Lab A assayed 33.26 mg, Lab B assayed 20.42 mg, Lab C assayed 20.62 mg, and Lab D assayed 16.3 mg of total resveratrol. The average finding of all four analytical labs in this specific example is 22.65 mg per capsule, again slightly above the label claim.
In November 2007, two commercial companies released conflicting findings about the potencies of resveratrol dietary supplements. One company published a chart showing that all resveratrol supplements tested (except the one it made) failed to meet full label claim. The names of the supplement companies this first company tested were not disclosed on the chart.
A second commercial company stated that most of the supplements it tested met label claim, but that several products, including a batch of Life Extension’s 20 mg resveratrol capsules manufactured in year 2006, did not. The first commercial company challenged these findings and claimed that their parallel study was at great variance with the second company’s findings.
Needless to say, we at Life Extension were quite disturbed that a claim has been made that one of our products may not have met our own exacting quality-control standards. This was particularly irksome because the resveratrol we use in our products is sourced from an expensive European whole red grape extract and costs many times more than Chinese materials used in most commercial supplements. So we set out to find out the facts about resveratrol analytical methods and how much resveratrol was really in the previous batches of our resveratrol products.
The initial analytical testing data of the specific 20 mg product in question showed that it fully met label claim. When the same batch of resveratrol was sent to other labs, however, the testing results showed varying levels of resveratrol that were below the stated label claim of 20 mg.
Understanding that each individual analytical lab often employs their own proprietary analytical methods for assaying complex botanical products, we then identified what we believed was the best laboratory that could perform repeat assays on all of the retained samples of every batch of a resveratrol-containing product we made dating back two years. This lab confirmed that just about every resveratrol product we made met full label claim, but that there were a few batches manufactured in the past that did not. Even though some experts claim that resveratrol is easily degradable, which means that older retained batches may have lost some of their original potencies, we decided to replace every single bottle that did not clearly meet full label claim using our new assay methodology. Each customer who was ever shipped a product from the batch in question was automatically sent a replacement. Since many of these products may have met full label claim when they were ingested, many customers may have been shipped free resveratrol.
As long-time members know, whenever there is a question about any product we sell, our policy is to automatically replace it. This occurred last year when a few customers complained about the consistency and color of Life Extension Toothpaste. While there was nothing wrong with the ingredients in the product, we automatically shipped over 3,000 tubes of a slightly improved (consistency and color wise) version of Life Extension Toothpaste to every purchaser at no charge. We are not aware of any commercial company in the world that follows these stringent customer-oriented policies.
When it came to resveratrol, we were determined to make sure that every milligram ever purchased from us was delivered to the customer, ergo our automatic replacement of any batch that had even a questionable assay result, no matter how old the batch was.
What Makes Life Extension’s Resveratrol Different?
In 2003, resveratrol became a household word as the front pages of major newspapers reported that this natural compound might significantly slow aging. Commercial supplement companies raced to formulate products that might enable humans to emulate scientific findings showing that resveratrol could mimic some of the favorable gene expression changes associated with caloric restriction.
Unlike commercial resveratrol companies, Life Extension Foundation went one step further. We took the resveratrol-grape seed product that our members were already using and tested it in the same type of gene expression study reported in the media. We wanted to see if this resveratrol-grape seed product could produce the same anti-aging gene expression changes that occur in response to caloric restriction in mice.
The results showed that our resveratrol-grape seed product, in the potency used by many Life Extension members, induced similar gene expression changes seen in response to caloric restriction in mice. What this means is that Life Extension’s novel resveratrol supplement has been documented in a scientific study to generate similar gene expression changes as caloric restriction itself. Since caloric restriction has been validated to have anti-aging and/or life span-extending effects in mice, rats, dogs, and monkeys, we believe that our resveratrol-grape seed product may produce similar effects in humans.
Caloric Restriction Promotes Longevity
Studies in long-lived humans indicate that there are definitive key predictors of longevity, such as low levels of blood glucose and insulin, stable weight during middle age, stress management, positive outlook, regular physical activity, and low body temperature. 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.5,60,61 Subsequent 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
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 It is these extremely favorable findings about caloric restriction that has scientists so excited about the longevity-enhancing potential of resveratrol as a caloric restriction mimetic.
Animal studies have demonstrated resveratrol’s safety at a human equivalent dose of approximately 300 mg/day.67 In laboratory studies, resveratrol has been found to inhibit human platelet aggregation. Theoretically, 100 mg or higher doses of resveratrol may increase the risk of bleeding in individuals who also use anticoagulant drugs, such as warfarin (Coumadin®), or antiplatelet drugs, such as clopidogrel (Plavix®).68
In the laboratory, resveratrol inhibits an important P450 liver enzyme (CYP3A4) involved in the meta-bolism of some common medications. While this interaction has not been observed in humans, a high dose of resveratrol (greater than 100 mg daily) could theoretically increase the bioavailability of certain medications such as statin drugs, calcium-channel blockers, benzodiazepines, and drugs used to treat erectile dysfunction.68 Individuals who use these medications should consult a physician before supplementing with more than 100 mg of resveratrol.
Scientists have not yet determined the safety of resveratrol-containing supplements during pregnancy and lactation. Until more information is available, pregnant and lactating women and young children should not use supplemental resveratrol.68
Resveratrol and resveratrol-derived compounds show tremendous promise in extending life span and fighting the diseases associated with aging, such as cancer and heart disease. Exciting research suggests that it may be possible to capture some of the life-enhancing benefits of caloric restriction through readily available resveratrol supplements. Resveratrol’s tremendous disease-fighting potential is evident not only from promising recent studies, but also from the efforts of well-funded pharmaceutical companies, who hope to create resveratrol-like drugs to combat aging-related disease.
For information on the dose of resveratrol you might consider taking, turn this page.
If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.