How do wonder drugs affect aging and disease?



by S. Mitchell Harman, Eons contributor

In the last few years, we have been reading and hearing a lot about "wonder foods" - mainly fruits and vegetables or their extracts -- that are said to help prevent cancer and heart disease, and preserve youth. Is there hard evidence that these foods really have beneficial effects on your health and longevity?

It turns out that the evidence for a group of active compounds called micronutrients is quite good, although scientists are only beginning to appreciate the incredible number of these compounds and the complexity of their interactions with one another.

What is a micronutrient?

Foods contain macronutrients that provide metabolic fuel (fats and carbohydrates) and the building blocks for cells and tissue (amino acids from protein). They also contain micronutrients that provide benefits via more subtle interactions with the body's chemistry. Whereas macronutrients must be consumed in quantities of many grams per day, micronutrients are active and potent in relatively tiny quantities, measured in milligrams or even micrograms.

Vitamins. The first micronutrients that scientists studied were vitamins: A (retinenes), B complex (thiamine, niacin, pyridoxine, folic acid, pantothenic acid, and B12), C (ascorbic acid), D, and K. In each case, they discovered that deficiencies in the vitamin were associated with a particular set of abnormalities, resulting in a disease. For example:


- Vitamin C deficiency causes scurvy, a disease characterized by weakness, joint swelling and pain, bruising, bleeding gums, tissue fragility, and poor healing.
- Low vitamin B12 is responsible for a severe disease called pernicious anemia.
- Vitamin D deficiency in children causes rickets, which weakens and deforms bones.

Although there are still debates as to optimal doses of these vitamins for various age groups and for men versus women, there is no question that these compounds are essential components of a healthy diet. With the exception of vitamin D (made by skin exposed to sunlight), none is synthesized in the human body and must therefore be supplied from outside sources.

Minerals. We know a great about why we need minerals and how they work. We need calcium (a major component of bone) and iron (needed for hemoglobin in blood) in relatively large quantities. Iodine is needed in modest amounts to make thyroid hormone. We require other minerals such as zinc, magnesium, and cobalt, in much smaller quantities, but they are still essential, mainly as enzyme components. Many important enzymes must be associated with one or more atoms of a particular metal, or trace element, in order to function properly. A healthy diet with a reasonable balance of meat, leafy vegetables, and fruit generally supplies the trace elements we need. However, many people also take mineral supplements, often in combination with vitamins.

Polyphenols. Most interesting to those of us concerned with aging and age-related diseases is this class of micronutrients that is less understood. It appears that plants manufacture polyphenols to help them resist stress, especially damage from direct sunlight. Polyphenols are large molecules containing multiple, six-carbon ring structures, each with three double bonds. The structures usually have extended or side groups of various types, connected to some of the carbon atoms. Side groups include:

hydroxyl (oxygen and hydrogen - OH characteristic of alcohols)
sulfhydryl (sulfur and hydrogen - SH)
amino (nitrogen and hydrogen - NH2)

These complex compounds also regulate enzyme action. Some increase the activity of enzymes in our cells that break down carcinogens. Some may regulate cellular gene activity, turning on genes that produce defensive enzymes or stimulating production of molecules that help repair damaged cell components.

Antioxidant action


There are many thousands of polyphenols in the plant kingdom, with many possible variations in their chemical structure. The compounds appear to act in different ways that may benefit those who consume them, but most important may be their role as antioxidants. Antioxidants are compounds that can remove an electron from a free radical molecule so that it becomes less reactive and therefore harmless to human tissue. We generate oxygen free radical molecules (also called reactive oxygen species, or ROS) and nitrogen free radicals (reactive nitrogen species, or RNS) in the course of normal metabolism. They also form when our cells are struck by a particle or wave of ionizing radiation (for example, cosmic rays or X-rays) or affected by toxic compounds in cigarette smoke and other sources. ROS and RNS can react with and damage proteins, nucleic acids (DNA and RNA), and lipids (fatty molecules) in our cells, which are vital to life processes.

There is increasing evidence that damage from free radical reactions plays an important causal role in a variety of diseases, including heart disease, cancer, and Alzheimer's disease. Cumulative free radical damage over many years seems to be a key element of the aging process. Our cells defend themselves against free radical damage in part by manufacturing a variety of antioxidant compounds, but we may also need abundant antioxidants in our diet to help protect us against ROS and RNS. Although the best-known antioxidant vitamins are C and E, many of the polyphenolic compounds in foods appear to be far more potent on a gram-for-gram basis.

We will focus on three familiar foods that contain powerful polyphonic compounds: green tea, red wine, and blueberries.

Green tea. Much has been written about the virtues of green tea. The Chinese and Japanese Have long believed that it provides important health benefits and increases longevity. In a study of 3,380 women who practiced the Japanese tea ceremony regularly, mortality rates were estimated to be only 55 percent of those in a standard population of Japanese women. In other Japanese epidemiological studies, green tea consumption has been associated with lower rates of cancer and has been reported to reduce the risk of heart disease.

In addition to acting as antioxidants, green tea polyphenols have been shown to promote the death of cancer cells in culture and inhibit the growth of tumor cells and new tumor blood vessels in animal models. They also appear to reduce inflammation, which may help lower the risk of cardiovascular disease. We do not yet know what role green tea might play in helping to reverse oxidative damage to lipids, proteins, and DNA or prevent and treat heart disease, cancer, and neurodegenerative diseases. Until we study these areas, we will have to rely on evidence that is not yet definitive regarding its benefits.

Red wine. Red wine is a "hot item" in health research these days (although it tastes best served at room temperature). As with green tea, red wine contain an incredible variety of

polyphenols with antioxidant properties. Red wine's polyphenol compounds -- such as resveratrol and flavonoids - have displayed antioxidant action in test tube experiments, so scientists suspect that red wine may be particularly effective in slowing atherosclerosis. One study also showed that red wine polyphenols inhibit the growth of a substance that constricts blood vessels and leads to vascular disease (red grape juice had a similar effect).

However, although numerous studies suggest that moderate consumption of any alcoholic beverage can reduce the incidence of coronary heart disease, there is no clear evidence yet that red wine is more beneficial for this purpose than other types of spirits. And, although another study showed that the polyphenol resveratrol prolongs the life of cultured yeast cells by up to 80 percent, we do not yet know whether it might have an effect on human longevity.

In summary, drinking red wine to protect your heart is an unproven strategy, but consuming one or two glasses of red wine daily with food may turn out to be beneficial.

Blueberries. Blueberries and their near relatives -- cranberries, wild chokeberries, and lingonberry fruit -- have the highest known concentrations of antioxidant compounds in the vegetable kingdom and appear to be effective in preventing oxidative cell damage. In one study with rats, blueberries reduced brain damage following a stroke, and other rat studies showed that blueberries, strawberries, and spinach reversed age-related declines in brain and motor function. Other studies on both rats and dogs indicate that consuming blueberries and other antioxidant-rich foods, such as strawberries and spinach, may help to preserve cognitive, memory, and motor function - and holds promise for treating Alzheimer's disease.

However, there is still a conspicuous lack of human data on the effects of berries -- or for that matter any antioxidants -- in preventing loss of brain function, heart disease, and other age-related illnesses. We do not know what amounts and types of antioxidants might be most effective, and it appears that several compounds in combination might be more effective than equal amounts of any single compound.

The Kronos Longevity Research Institute is conducting research to validate and standardize new, non-invasive ways to measure oxidative stress in humans. Later, we hope to use these techniques to discover what doses and combinations of antioxidants are most likely to produce clinical benefits. Then, the next step will be to do large trials to measure the effects of these combinations on disease prevention and normal aging.

In the meantime, the advice we give our friends and supporters is to consume a diet rich in colored fruits and vegetables, with at least one hearty serving of berries every day.


S. Mitchell Harman, MD, PhD, is director and president of the Kronos Longevity Research Institute, a not-for-profit, 501(c)(3) organization that conducts state-of-the-art clinical translational research on the prevention of age-related diseases and the extension of healthier human life. If you would like to know more about KLRI or its research, please visit their website at www.kronosinstitute.org or call 866-840-1117.