By Benjamin V. Treadwell, Ph.D.

When you think of plants, what comes to mind? Color? Beauty? Maybe sources of food and essential nutrients? Most of us, however, don’t picture these silent, immobile life forms defending themselves against their enemies.

The term "phytoalexin," from the Greek "alexin" for a protecting substance, describes their weapons. It was coined almost 70 years ago by plant pathology pioneers Muller and Borger, to designate antibiotic-like compounds produced by a plant in response to an invading bacteria, virus or fungus.

So, what does that mean to human life forms?

Famous Phytoalexin
Of the many phytoalexins reported in scientific literature, one of the best known and most studied is a polyphenolic compound known as resveratrol. Some of you may be familiar with this compound, which is present in red wine (derived from the skin of the grape), as well as produced by a variety of plants.

You may also remember that it was the subject of two issues of the Juvenon Health Journal earlier this year (Stress for the Best: Can Resveratrol Make Us Healthier?; Resveratrol, Revisited: Stronger Bones and Tumor Prevention Combined). Thanks to new findings related to type II diabetes, resveratrol is in the spotlight again.

Following the Food Chain
One of the fundamental theories about resveratrol is that it appears to improve a plant’s chances of survival by triggering a biological response, shifting energy from non-essential synthetic to life-essential biochemical pathways. In other words, if a plant is being attacked by a fungus or bacteria, it produces resveratrol, which shifts the plant’s metabolism into a fighting mode. The plant becomes more efficient than normal at producing and conserving energy because it needs all the energy it can muster to operate its defense system.

How does this affect the animals and humans farther up the food chain? We know we require plants, the original source of fuel and nutrients, for survival. But our connection appears to be even more intricate. There may be a mechanism in place to shift the biological system of the animal into a metabolic state compatible with what is available from the food chain.

First, by eating a stressed-out plant, an animal seems to get the message that members of this food source are about to be scarce. Second, the resveratrol from the plant also appears to affect animal cells, in vitro (culture) and in vivo (live animal), the same way it does plant cells.

Healthier Energy Balance
Since the 1930’s, experiments with yeast, flies, worms and rats have shown that a calorie restricted diet (about 40% fewer calories than normally consumed per day) significantly extends lifespan. Similar to resveratrol in plants, the calorie restricted diet acts on biochemical pathways — particularly those under the regulation of the insulin-producing beta cells of the pancreas — to promote a healthier, more disease-resistant animal.

More recent experiments have shown that CR also has a profound effect on improving the animal’s energy homeostasis (energy balance) as well as its overall health. Does the same apply to resveratrol?

A number of studies have been published, demonstrating the effects of resveratrol on animal metabolism. When mice were fed an unhealthy diet high in fat, they developed diabetes and heart disease, and were generally unhealthy and lethargic. Remarkably, however, when mice were fed the high-fat diet supplemented by the phytoalexin resveratrol, they were as healthy as mice fed a nutritious diet. In this research, it appears that resveratrol is functioning as a CR mimetic, improving metabolic regulation at the level of insulin production.

Type II Diabetes
A diet high in fat dramatically increases the chances that an animal (or human) will develop a resistance to insulin. Type II diabetes is characterized by this resistance to the action of insulin on muscle, fat and liver tissue cells, which normally triggers the uptake of glucose from the blood vessels. Consequently, blood-glucose remains high, leading to pathology.

Recent research, both in vitro and in vivo, demonstrated that the phytoalexin, resveratrol, can prevent or attenuate the diabetic (insulin resistant) condition. (See this issue’s "Research Update.") The investigators found that resveratrol activated one or more SIRT enzymes that eliminated a fat-associated inhibitor of insulin action (protein tyrosine phosphatase 1B).

The net result of resveratrol’s action was to convert muscle, fat and liver tissue cells to an insulin-sensitive state. Subsequently, this allowed glucose to be removed from the blood, returning the tissues to energy homeostasis.

Pathway for People
Beyond resveratrol’s potential as a therapy for type II diabetes, this research identifies a possible common pathway, acted on by either a calorie restricted diet or the phytoalexin, resveratrol, to improve energy homeostasis. This study and others strongly implicate the insulin metabolic pathway as at least one of the factors involved in health and longevity.

The question remains as to whether the encouraging results obtained with animal and cell culture research will hold true for people. The answers may be available soon; there are currently a number of studies examining the effects of resveratrol on type II diabetes as well as other disease states in humans.

Diabetes currently affects more than 170 million people worldwide and will prospectively affect more than 353 million by the year 2030. Type II diabetes, which accounts for over 90% of the cases, is characterized by the resistance of target tissues to insulin stimulation.

In the October issue of Cell Metabolism, a group of Chinese researchers published the results of their study that demonstrates a dramatic improvement in the response of cells to insulin after treatment with the plant-derived polyphenolic compound, resveratrol. The investigators were interested in determining the mechanism through which resveratrol elicited the increase in insulin sensitivity.

They examined the effects of resveratrol on various components of the insulin-signaling pathway and discovered the enzyme SIRT1, previously reported to be activated in cells exposed to resveratrol, was one cellular component necessary for the response. Further work showed that SIRT1, in turn, blocked the production of another cellular enzyme, PTPB1, at the gene level. Since PTPB1 interferes with insulin action, its removal by resveratrol-induced SIRT1 results in the reactivation of the insulin pathway and a decrease in insulin resistance.

Click here to read the full abstract.
"SIRT1 Improves Insulin Sensitivity under Insulin-Resistant Conditions by Repressing PTP1B"
Cell Metabolism, Vol 6, 307-319, 03 October 2007

This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

QUESTION:  I’ve followed Dr Ames' work the past few years and I take Juvenon. I was looking at your other products, as I have been taking GNC and Doctor's Trust vitamins for men and wanted to see how yours compared. Then I read an article in the November, 2007 issue of Reader's Digest, "The Vitamin Myth," which quotes several recent studies, saying that taking large amounts of 10 vitamins and minerals can be harmful to you. I'm just wondering what your thoughts are on these studies. Thanks. — C.

ANSWER: Two of the issues with studies claiming to show detrimental effects from taking some vitamins are the methods used and how the variables were controlled. Many are meta-analysis studies, where investigators examine previous work, then try to consolidate the results into a meaningful conclusion. Meta-analysis is not the strongest of scientific methods, primarily because of so many uncontrolled variables.

There are also numerous reports, published in scientific journals, demonstrating significant benefits from certain vitamins. As we age, a gradual imbalance develops in the oxidant-antioxidant redox state of our cells, favoring a more oxidized condition. Certain supplements may improve this condition and our cellular health, helping to maintain our overall health.

I think the bottom line is not to take vitamins in excess. But the amounts present in multiple vitamin-mineral supplements are, for the most part, quite safe.

Send your questions to AskBen@juvenon.com.
For more questions and answers, go to juvenon.com/product/qa.htm.

Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor and member of Juvenon's Scientific Advisory Board.