“Is the Free-Radical Theory of Aging Dead?”

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The Story

“Is the Free-Radical Theory of Aging Dead?”
by Melinda Wenner Moyer
Scientific American, February 2013

The Pitch

Could vitamins kill you?

The dark side of vitamins

Toxic antioxidants

There’s no denying that vitamins can work medical wonders. Dozens of observational studies have linked higher vitamin D intake to lower risks of cancer, heart disease and bone conditions. Earlier this year, the U.S. Centers for Disease Control and Prevention reported that people who consume large amounts of alpha-carotene, a vitamin found in pumpkins and carrots, are 40 percent less likely to die prematurely than people who consume the least. And mega-doses of vitamins C, E, beta-carotene and zinc with copper have been shown to lower a person’s risk of developing age-related macular degeneration.

These benefits probably come as no surprise. After all, they are the reason that Americans spend more than $2 billion each year on supplements. But there is another side to vitamins, too. A growing body of research suggests that in certain circumstances, some vitamins might actually heighten your risk for cancer and premature death.

In October, a clinical trial follow-up of a randomized prospective study of 35,000 men, which was published in the Journal of the American Medical Association, reported that men who took 400 units of vitamin E (a popular dose found in thousands of supermarkets and drugstores) every day for up to seven years had a 17 percent greater risk for developing prostate cancer than men who did not. This was a shocking finding, as previous research had suggested that vitamin E, an antioxidant, might protect against prostate cancer. A 2007 meta-analysis of 47 clinical trials published in JAMA reported that beta carotene, vitamin A and vitamin E supplements increase an individual’s risk of death by five percent. Two randomized, prospective studies from the 1990s, which have since been confirmed through repeated followup, reported that beta carotene and vitamin A supplements increase the risk that smokers will develop lung cancer and die.

How is this possible? Most of these vitamins are antioxidants, which mop up free radicals circulating through the body. Since the 1960s, most biologists have agreed that free radicals—high-energy particles that are byproducts of cellular energy metabolism—are dangerous. In fact, according to the well-established “free radical theory of aging,” free radicals are considered are one of the key reasons we get old: the particles build up over time and injure our tissues and organs, causing our bodies to slowly deteriorate and become diseased.

But what these new studies tell us is that scientists may not understand free radicals—or, for that matter, aging—as well as they think they do.

In fact, recent lab research suggests that free radicals might sometimes lengthen lifespan.

In a December 2010 study in PLoS Biology, biologists at McGill University bred mutant C. elegans worms that produced excess amounts of superoxide anion, a free radical that transforms into other free radicals including hydrogen peroxide. Although the free radical theory predicts that these worms should die young, they lived, on average, 94 percent longer than normal worms. Treating them with the antioxidant vitamin C prevented this near doubling of lifespan. In a follow-up study, the researchers exposed normal worms from birth to low levels of a common weed-controlling herbicide that initiates free radical production. The worms lived 58 percent longer than untreated worms, unless they were simultaneously treated with antioxidants. Finally, a study published in October 2011 reported that an anti-cancer drug currently in clinical trials extends lifespan in worms in part because it induces free radical production.

Scientists do not dispute that exposure to large amounts of free radicals—such as through accidental radiation exposure—can be deadly (and as we know, antioxidant vitamins aren’t always bad). But in certain circumstances, free radicals may play a role in the body’s protective response to tissue degeneration. A study published in June 2011 by Cornell scientists suggests that free radicals act as stress signals, activating a gene called CEH-23 that turns on other genes involved in damage repair. Free radicals do seem to play a key role in aging—they are more prevalent in aging tissues than in young tissues, and their numbers are also elevated in cells affected by conditions like Alzheimer’s, cancer, diabetes and atherosclerosis—but they may not always cause it. Sometimes, they may help prevent it.

No one yet knows how, exactly, this emerging shift in perspective will change preventive medicine. But some anti-aging strategies may ultimately be more successful if they stimulate free radical production rather than stifle it. In fact, one such intervention already exists: It’s called exercise. Scientists have long known that exercise boosts free radical levels, but they assumed that this occurred in spite of its overwhelming benefits. Now, researchers are starting to believe that exercise is good precisely because it causes oxidative stress. In a small study published in 2009 in the Proceedings of the National Academy of Sciences USA, nutritionists at the University of Jena in Germany asked a group of 40 healthy young men to exercise every day for four weeks. Half took moderate doses of vitamins C and E every day, while the other half did not. After the trial, the vitamin-free athletes experienced marked improvements in insulin sensitivity (which reduces type 2 diabetes risk) and had chemicals in their blood indicative of a boost in natural defenses against oxidative stress. The subjects who took antioxidants, however, had neither.

I would like to write a feature for Scientific American that presents the science behind the notion that vitamins can be dangerous. I’ll discuss the ways in which scientists are reconsidering the role that free radicals play in the body and revising their understanding of aging. Please let me know if you have any questions. Thank you!

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