WASHINGTON—To decrease your risk of cancer, don't count on antioxidant supplements, a panel of researchers said here at the annual meeting of the American Association for Cancer Research. But assessing antioxidants' role (and that of many other dietary supplements) in preventing disease has been notoriously difficult.

Antioxidants, such as vitamin C, vitamin E, beta carotene, lycopene and selenium, have worked their way into the public imagination—and even the minds of many clinicians—as boosters of overall health with cancer-fighting powers, given their ability to absorb free radicals, which can do damage to genetic material, as well as what's been shown in the lab.

Studies of these compounds in vitro present "a lot of reason to believe" they would help prevent cancer in vivo, said Alan Kristal, of the Fred Hutchinson Cancer Research Center in Seattle, at the April 19 panel. But human bodies are a lot more complex than isolated growth factors in petri dishes. And humans—even those in clinical trials—often don't follow the rules. 

"Antioxidants interact not only with each other but also with other environmental factors," Kristal noted. This is problematic because, as he explained, "people who use supplements use lots of supplements, they don't just use one." So if, as in some previous studies of several compounds, different antioxidants were shown to have a negative or positive impact on cancer risk, it is often the same individuals enumerated in tallies of each compound's impact, rather than individual groups being isolated and given only one compound.

Even in randomized, blinded clinical trials, many subjects will still take multivitamins or other supplements on their own in case they are in the placebo group, noted both Kristal and Regina Santella, of Columbia University's Mailman School of Public Health in New York. In one of her trials, subjects in the placebo group were taking their own vitamins because they could tell if they had been given the active or placebo "vitamin" pills just by the smell of the bottle, she said.

And many health-related study designs often have trouble enrolling and retaining people who aren't already proactively managing their health and diet. "Factors that predict participation are going to predict not getting the disease," Kristal explained. So in a case-control study, in which a group of cancer patients' antioxidant intake is measured against that of a "control" population, researchers might be comparing two groups who would have very different baseline health levels to begin with.

Some research has shown slight possible protective effects in various subgroups that have higher cancer risks, such as smokers. There is some evidence that vitamin E can help protect men who smoke against prostate cancer (though Kristal said the findings were "by no means convincing"). And small doses of beta carotene have looked moderately protective against lung cancers in ferrets exposed to tobacco smoke. Larger doses of the compound, however, actually appeared to promote growth of latent tumors in the animals, Santella noted. "One of the potential problems is that we've been using the wrong dose of these compounds," she said. But the understanding of the actual mechanisms by which these antioxidants are working remains largely unknown.

It might also be that hunches about antioxidants' protective effects aren't entirely off base, but that their value is best accessed by eating the whole foods they come from, such as broccoli, spinach and carrots. "Thinking that one component in a mixture is going to be the answer is probably too simplistic," Santella said. In one animal study, rats that were given tomato powder (a natural source of lycopene) were better protected against prostate cancer than those given a higher dose of the compound in isolated supplement form.

But trying to drill down on whole-foods intake in formal studies can be just as challenging as testing supplements. "Measures of dietary intake are worthless," Kristal said. Not only do people have difficulty recalling what they ate, but also a range of other factors, such as preparation and portion size, can make a big difference in the actual content of many of these compounds.

Many consumers, however, remain dedicated to antioxidants and other supplements as a way to fend off cancer. Adults in the U.S. spend upward of $9 billion a year on vitamins, pointed out New York Times health writer Tara Parker-Pope, who noted that she, personally, had been disappointed to learn through her own research what Kristal concluded at the panel discussion: "There's really no association between antioxidants and cancer risk in the general population."

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