By Benjamin V. Treadwell, Ph.D.

How many times have you been told to eat your fruits and vegetables if you want to be healthy? Whether the advice comes from your parents or a health professional, the evidence to support it is obvious: people who consume more of these foods are less prone to disease.

One of the reasons, as discussed in May's Juvenon Health Journal, may be resveratrol. Many plants contain the nutrient resveratrol. It's our subject again this month because recent laboratory studies suggest resveratrol may be a therapeutic strategy for prevention of osteoporosis. (See "Research Update.") 

Quick Review of Resveratrol

Over the past hundred-plus years, research has discovered a variety of substances contained in plants that the cells of our body require to convert food to energy. These substances also allow cells to make key structural components for maintaining the health of our eyes, skin, bone, muscle and brain.

Today, we can purchase many of these essential nutrients in pill form, labeled multiple vitamins and minerals. Currently, there are well over 40 of them, many originally plant-derived. It appears there are several more that have not yet been defined or characterized, among them resveratrol.

Resveratrol is present in many plants and especially concentrated in the skin of grapes. It is similar in structure to the catechins present in tea (especially green tea), as well as compounds present in richly colored berries and fruits (blueberries, pomegranates) that also have significant support as health-promoting agents. Plants, it is believed, synthesize these compounds to use as a weapon against invading pathogens like fungi, bacteria and viruses. 

Multi-Tasking Resveratrol
Recent animal and cell culture studies, examining the effects of this polyphenolic compound on other organisms, have indicated that resveratrol may help to inhibit cancer growth and tissue-destructive inflammation. Laboratory studies also suggest that it may help to improve cardiovascular health and blood pressure, as well as cholesterol levels, and even to extend the lifespan of a number of species of animals, including mice.

The details as to the mechanism involved in these resveratrol-induced benefits are complex and currently under intense investigation. (For more on this topic, see Juvenon's Health Journal article titled: Stress for the Best: Can Resveratrol Make Us Healthier?; Plants and their Magical Health-Promoting Ingredients and Exercise, Calorie Restricted Diet, Red Wine and the Hybrid Car.)

Osteoporosis and HRT
Osteoporosis is a decrease in bone strength due to loss of bone mineral and structural components. It is a significant issue associated with aging in both sexes, especially in post-menopausal women.

Several years ago, bone loss was linked to a decrease in serum levels of the hormone estrogen, a post-menopausal phenomenon. The medical profession began treating post-menopausal patients, who exhibited early signs of osteoporosis, with estrogen. This hormone replacement therapy (HRT) did significantly inhibit progression of the disease.

Unfortunately, recent studies have shown this form of treatment to be associated with considerable risk, including an increase in cardiovascular disease and cancer. These results have prompted the medical profession to be more cautious in the treatment of osteoporosis with HRT as potential risks may offset the benefits. 

Osteoporosis and Resveratrol
Resveratrol, according to another recent laboratory study, has the potential of helping to prevent osteoporosis without the health risks associated with HRT. Demonstrating that this plant compound is a phytoestrogen, which can bind to and activate estrogen receptors, was the impetus to investigate the potential role resveratrol may play in bone metabolism.

Studies were carried out in cell cultures as well as animals that were susceptible to bone loss (ovariectomized rats). Collectively, the results demonstrated a number of bone-forming activities associated with resveratrol treatment.

Resveratrol turns on genes involved in bone formation and turns off genes involved in bone destruction. The result is the conversion of precursor bone cells to bone-forming cells (osteoblasts), as well as the inhibition of the production of bone-destroying cells (osteoclasts). The net result in bone is anabolic. In other words, the bone is getting stronger with an increase in bone mineral and bone structural components or proteins. 

Tumor Suppressing Bonus
What sets resveratrol apart from HRT? While both promote the production of bone strength and inhibit osteoporosis, resveratrol, rather than increasing the risk of cancer, prevents tumor growth. Why the difference?

Although resveratrol, like HRT, activates a biochemical pathway to promote bone-forming cell growth and inhibit bone-destructive cell growth, it simultaneously activates a pathway that culminates in the synthesis of a tumor-suppressor protein, FOXO3A, which accumulates in the cell's nucleus.

Resveratrol's Future
The bone-forming property associated with resveratrol, without the cancer risks associated with HRT, would appear to make this compound an ideal therapeutic strategy for the prevention of osteoporosis. However, the studies to date, although very encouraging, were performed on cell cultures and animals. To be appropriate as a therapeutic for human use, future studies will have to demonstrate similar effects in clinical trials.

Nevertheless, resveratrol is a compound of significant interest, with respect to its many purported health benefits, including improved cardiovascular health, cancer prevention and anti-aging. In addition, there are virtually no reported negative side effects in studies using very large doses.

Many following this research believe that either this compound or more potent synthetic derivatives of resveratrol will be future therapeutics. The work associated with resveratrol has already led to exciting discoveries that should help promote the development of therapeutics for a variety of disease states.

An article published on May 18, 2007, in The Journal of Biological Chemistry, examines the effects of the plant-derived polypheonolic compound resveratrol on a common disease of the bone, osteoporosis.

Two major developments stimulated this work. First, the Women's Health Initiative recently found increased risks of breast cancer and cardiovascular disease with hormone replacement therapy (HRT) for treatment of osteoporosis in the most susceptible segment of the population, post-menopausal women. Second, recent discoveries have identified resveratrol as a compound that can bind to and activate the estrogen receptor and potentially function in a manner analogous to HRT in improving bone strength.

The present laboratory study re-enforced the compound's potential. Resveratrol was found to exhibit bone-protective effects equivalent to those provided by HRT while decreasing the risk of breast cancer in the in vivo and in vitro models.

To read the abstract, click here.
"Forkhead proteins is critical for BMP-2 regulation and anti-tumor activity of resveratrol"
J. Biol. Chem, 10.1074/jbc.M702452200

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 enjoy the regular updates. I do, however, have an issue with the previous article in which you stated that pomegranates are a good source of resveratrol. While pomegranates are a good source of anthocyanins and other related nutrients, I have not seen published data that suggests they are a particularly good source of resveratrol. Far and away, the best source is red wine. If you know of any data to the contrary, please send me the references so that I can expand my own knowledge on the subject. — Dr. B.

ANSWER: Thank you for calling this to my attention. I contacted the senior investigator of a recent study that made this claim (and from which I obtained my information). Neither he, nor I, has been able to find a published report confirming high levels of resveratrol in pomegranates, although research does show that pomegranates contain a variety of other highly nutritious phenolic compounds. When/if we do find documentation (and we will continue to search), I'll be happy to send it to you.

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.