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The Rusting Body

Antioxidants for what ails you?

by John F. Lauerman

Illustration by Tracy Mitchell

Once, on a family trip cross-country, we stopped the station wagon outside Amarillo, Texas, to view a collection of old Cadillacs planted vertically halfway into the ground. I was amused at the time, but had no idea just how much I had in common with those aging hulks. When a car rusts, oxygen latches onto and oxidizes the iron, changing it into a material much weaker, dustier, and flakier than the original frame of the shiny vehicle we drove out of the dealer's showroom. The same thing happens to human bodies, and a large body of scientific research indicates that it is a long-term losing battle.

Part of the metabolic process in all cells generates a certain number of free radicals: substances with a strong tendency to tightly bind to other molecules in ways that corrupt or destroy them. Most of these free radicals contain oxygen, a highly reactive element the body uses to make energy. Once a molecule has been oxidized, the damage steadily spreads as unpaired electrons snag and corrupt other proteins.

Recent research suggests that oxidation may be the major force behind aging. Normal metabolism, the biochemical process that gives us the energy to read this article, yields waste products in the form of free radicals that threaten tissues throughout the body. But there are signs that antioxidants--substances that bind with these reactive molecules--can counteract the aging process. Despite their technical-sounding name, antioxidants are easily obtained. Fresh fruits and vegetables eaten raw or lightly steamed or boiled, grains, nuts, seeds, fish oil, and starches such as rice, potatoes, and cereal, are all good dietary sources of antioxidant vitamins, and the mineral selenium, another antioxidant, is found in shellfish, meat, poultry, egg yolks, garlic, and Brazil nuts.

Although we still lack precise understanding of how antioxidants prevent disease, there is growing evidence that they may stave off numerous age-associated conditions. Cholesterol, for instance--an otherwise useful substance normally associated with the transport of fat molecules in the bloodstream--is frequently found in oxidized form in the arterial plaques that block heart vessels and cause heart attacks. Research from around the world shows that relatively higher blood levels of the antioxidant vitamins A, C, and particularly E are associated with lower rates of cardiovascular disease.

Cancer also appears to be linked to oxidation. Researchers in Arizona found that the group of volunteers who received a daily 200-microgram dose of selenium for four and a half years had a cancer death rate 50 percent lower than that of the group that received a placebo. Prostate cancer, which is very common in older men, caused 63 percent fewer deaths among the selenium-takers. A later Harvard study of 33,737 men reinforced the findings on prostate cancer.

Other studies suggest that antioxidants may help reduce the risk of Alzheimer's disease, delay complications of diabetes, and even blunt harmful side effects of certain psychoactive medications. What's more, certain antioxidants, like vitamins C and E, appear to be relatively free of side effects themselves.

If even half of what is currently claimed were true, we would seem to be in possession of an important preventive tool. Shouldn't everyone be using supplementary antioxidants, or at least boosting their intake as part of a routine diet?

But with antioxidants, as with much else, more is not necessarily better. Bruce Demple, professor of toxicology at the Harvard School of Public Health, cautions that there is reason to believe the body has learned how to use its "rust," and may even require it to perform some tasks. "Some free radicals are good for you," he says. "They play a role in the immune response, and they're part of the normal surveillance system that clears out precancerous cells. They are also used in signaling systems in ways we are only beginning to understand."

Nitric oxide, for example, acts as a key regulator of blood pressure, Demple explains. If antioxidants were stored in such high levels that this free radical were neutralized, many important body functions would fail. "There are all sorts of reasons to proceed with caution," he concludes.

Demple's words are borne out by a few studies raising the unexpected possibility that beta carotene, a supposedly innocuous antioxidant, actually increases the rate of lung cancer in smokers. The Seattle-based Carotene and Retinol Efficacy Trial (CARET) was designed to see whether daily oral administration of 30 milligrams of beta carotene and 25,000 IU [international units] of vitamin A (five times the recommended daily allowance) would decrease the incidence of lung cancer in long-term heavy smokers and people exposed to asbestos in the workplace. The researchers were shocked to find 36 percent more lung cancers and 17 percent more lung-cancer deaths among those taking beta carotene and vitamin A than among those receiving a placebo.

But CARET was a study of synthetic high-dose beta-carotene supplements in a population already at high risk for lung cancer, notes Walter Willett, D.P.H. '80, M.D., professor of medicine and Stare professor of epidemiology and nutrition at the school of public health. Willett suggests that differences between these supplements and the natural mix of carotenoids found in foods may have been responsible for the excess cancers. He says that smokers may want to avoid megadoses of beta carotene, but stresses that nothing in the CARET study negates the benefits of seeking out sources of natural antioxidants, preferably from fresh fruits and vegetables. (Even these measures, however, will not be sufficient to offset the enormous adverse effects of smoking.)

Although Willett believes the jury is still out on antioxidants' possible impact on Alzheimer's disease and cancer, evidence is strong that vitamin E can help prevent heart disease. A pair of 1993 studies he directed showed that vitamin E supplements were associated with a decreased risk of heart disease in both men and women. "We thought that supplementing the diet with vitamin E might block the oxidation of cholesterol," he says. "We saw in our studies that 400 IU of vitamin E was giving some protection, but metabolic studies suggest that 800 is better than 400. Something around 400 or 800 IU as a daily supplement probably makes sense."

Caution is always appropriate when dealing with substances that haven't been studied over the long term, and, as Willett notes, "Biology always turns out to be more complicated than we anticipate. We can't say for sure that we've eliminated all the possibilities of adverse outcomes from vitamin E, but," he points out, "you could say that about any drug on the market. Even though absolute proof is not yet at hand, I think there is a rational basis for taking vitamin E in particular for anyone at risk for heart disease--which includes almost all people over 40 in the United States. We should still keep our eyes on forthcoming studies of vitamin E, but from what we know, I think there is a much better chance that it will do good than harm."

John F. Lauerman, a contributing editor of this magazine, is coauthor, with Thomas Perls, M.P.H. '93, M.D., and Margery Hutter Silver, Ed.D. '82, of Living to 100, published this month by Basic Books.

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