Life Extension Magazine

Life Extension Magazine March 2007

Report

Growing Evidence Links Resveratrol to Extended Life Span

By Laurie Barclay, MD

Extending human life span

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.

Practical Considerations for Optimal Supplementation

While plentiful data attest to resveratrol’s potential benefits for health and longevity, certain practical concerns must be addressed to obtain its optimal effects as a dietary supplement. These include resveratrol’s stability, shelf life, dosage, and the variability of different available preparations. Even today, much remains to be learned about the pharmacokinetics of resveratrol—that is, how it is absorbed, utilized, broken down, and excreted in humans.

Bioavailability

Laboratory and animal studies clearly show that resveratrol and its derivatives are biologically active. However, Dr. Zhao-Wilson notes that there are “significant issues related to what is currently known about resveratrol’s bioavailability—it appears to be rapidly metabolized in humans.” Dr. Sovak agrees, commenting, “One problem with resveratrol is that we do not know that much about its resorption and bioavailability in humans, but as expected, the compound is rapidly metabolized and excreted.”

Scientists are exploring ways to optimize resveratrol’s pharmacokinetics. For example, in the Czech Republic, where resveratrol has been approved as a nutritional supplement, Dr. Sovak and his colleagues conducted a pilot study in humans comparing high-purity, pharmaceutical-grade resveratrol to resveratrol glycon, the natural form of resveratrol extracted from the Polygonum plant. Of the two preparations, resveratrol glycon was found to be more easily absorbed in the body and to have better pharmacokinetics.

Another method under investigation to improve resveratrol’s bioavailability is administering it concomitantly with plant-derived flavonoids. Numerous studies suggest that the bioflavonoid quercetin slows the inactivation of resveratrol, thus improving its bioavailability.46,47 A novel type of quercetin, quercetin chalcone, demonstrates superior absorption and solubility, and may thus be the optimal form of this bioflavonoid.48

Stability

Previously, scientists were concerned that the clinical usefulness of certain resveratrol-encapsulated preparations could be limited by poor stability, limited shelf life, or exposure to light and air. However, recent stability studies by Dr. Sovak and his colleagues at the Czechoslovak company Interpharma Praha have demonstrated these concerns to be unjustified. Resveratrol is generally stable for at least two years and does not require special packaging or storage.49

Purity

Not all resveratrol preparations are of equal quality. “As for the variability of different available preparations, this is always an issue with respect to manufacturing and quality control associated with dietary supplements in general,” says Dr. Zhao-Wilson. “It is ‘buyer beware,’ and one must find a high-quality source with a vested interest in providing consumers with the best available products and scientific evidence to back them up.”

Dr. Sovak agrees, and recommends only pure forms of resvera-trol for study and consumption. Interpharma Praha has developed technology to produce high-purity resveratrol and resveratrol glycon according to GMP (good manufacturing practice) standards.

Dosage

In addition to exploring resveratrol’s many potential health applications, researchers are also trying to determine the optimal dose needed to capture its benefits.

“There have been insufficient studies to date in humans to address issues related to optimal dose,” notes Dr. Zhao-Wilson. “Extrapolation of optimal dose from animal studies to humans is always more of an art than a science, and the appropriate studies still need to be done. Nevertheless, reasonable assumptions can be made, and there is even evidence that low doses may be effective for certain conditions.”

Many commercially available supplements provide 20 mg of resveratrol daily. The rationale behind this dosage is that prior to the widespread use of pesticides, French red wine contained approximately 20 mg of resveratrol per liter, and those drinking about a liter daily appeared to derive the cardioprotective benefit associated with the French paradox. Now that the resveratrol content in red wine has decreased to 90 micrograms per fluid ounce,50 a 20-mg (20,000-mcg) resveratrol supplement contains approximately 220 times the amount of resveratrol in one fluid ounce of red wine, or about 41 times the amount in one glass of red wine.

Studies by BioMarker have shown that resveratrol offers benefits for gene expression and longevity in a variety of species using a dosage comparable to 20 mg daily in humans. However, given the extraordinary findings of recent studies using high-dose resveratrol supplements—and their profound implications for human health—some resveratrol researchers and other health-conscious people are now consuming even larger daily dosages.

As for who should supplement with resveratrol, leading researchers maintain that in addition to benefiting patients with specific disease conditions, resveratrol may confer broad-spectrum protection to anyone seeking to live a long life in optimal health.

According to Dr. Zhao-Wilson, “the properties associated with resvera-trol appear to be largely protective—cardioprotective, neuroprotective, anticarcinogenic, anti-inflammatory—and the current data suggest that most people could benefit from dietary supplementation with resveratrol obtained from a high-quality source.” Dr. Zhao-Wilson adds that resveratrol is generally safe when taken in conventional dosages.

Dr. Sovak similarly recommends resveratrol as a health-protective agent, noting that resveratrol may be helpful both alone and in combination with other antioxidants, such as epigallocatechins derived from green tea.51,52 Turn to the next article for more precise information about optimal resveratrol dosing.

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:

  1. suppress aberrant cellular proliferation
  2. induce DNA repair
  3. enable insulin to assist glucose uptake into cells
  4. facilitate production of beneficial high-density lipoprotein (HDL).

Examples of detrimental genes that are “turned up” during normal aging include those that:

  1. induce excess production of potentially harmful low-density lipoprotein (LDL) and cholesterol
  2. override normal patterns regulating cell division
  3. promote excess production of insulin and inflammation
  4. interfere with apoptosis (programmed cell death) of cancer cells.

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 and metformin. The implications of these findings—which have made headline news around the world—is that it may someday be possible to engineer our genes in a way that will make us invulnerable to atherosclerosis, cancer, dementias, arthritis, and all other age-related disorders, as well as aging itself. The net effect would be a radical extension of the healthy human life span.

We at Life Extension hope that you are as excited as we are to be part of this fantastic voyage into the outer frontiers of medical research. We urge you to continue to support us so that we can play an ever-increasing role in funding this type of revolutionary scientific research.