Antioxidants Could Increase Cancer Rates

29 January 2014 2:00 pm
Jocelyn Kaiser
Jocelyn is a staff writer for Science magazine.

Antioxidants Could Increase Cancer Rates

Many people take vitamins such as A, E, and C thinking that their antioxidant properties will ward off cancer. But some clinical trials have suggested that such antioxidants, which sop up DNA-damaging molecules called free radicals, have the opposite effect and raise cancer risk in certain people. Now, in a provocative study that raises unsettling questions about the widespread use of vitamin supplements, Swedish researchers have showed that moderate doses of two widely used antioxidants spur the growth of early lung tumors in mice.

Some cancer specialists caution against basing public health advice on the study, published online this week in Science Translational Medicine. “You can’t extrapolate from this study to make a recommendation to people,” says Barry Kramer, director of the Division of Cancer Prevention at the National Cancer Institute in Bethesda, Maryland. He notes that the science of antioxidants is complicated and that the results of mice studies often don’t apply to humans. Still, Kramer and others say the new findings demand further exploration.

The observation decades ago that people who consumed lots of fruits and vegetables had less cancer suggested that the antioxidants in these foods might be protecting them. But in the 1980s, researchers launched two large clinical trials to test whether the antioxidants β carotene (a vitamin A precursor), vitamin A, and vitamin E protect smokers from lung cancer—and found more cases of lung cancer in volunteers taking β carotene, leading one trial to end early. A more recent trial testing vitamin E and selenium to prevent prostate cancer was stopped when prostate cancer turned out to be more common in the vitamin E group.

The Swedish researchers, led by Per Lindahl and Martin Bergö of the University of Gothenburg, studied two antioxidants: n-acetylcysteine (NAC), a water-soluble drug used to thin mucus in people with lung disease, and fat-soluble vitamin E. They gave mice genetically engineered to develop lung tumors a dose of NAC comparable to what a patient would receive or chow containing about 10 times more vitamin E than is in ordinary mouse food. “A lot of vitamin pills contain a lot more than that. It’s a conservative dose,” Bergö says.

Compared with mice on a normal diet, the mice consuming the antioxidants developed more lung tumors, their tumors were more aggressive, and they lived only half as long. Follow-up studies suggested that by reducing reactive oxidative species and DNA damage in the cell, the antioxidants turn down a gene, p53, that is key to keeping cell growth in check and is often inactivated in cancer. For example, p53’s protein stops the cell cycle so enzymes can repair damaged DNA and triggers apoptosis, or self-destruction, in severely damaged cells. In cancer cells in which p53 had been turned off, Lindahl and Bergö found, the antioxidants had no effect on cell proliferation.

The implication, Bergö suggests, is that people at high risk of cancer—such as smokers—and others who have incipient tumors should avoid taking extra antioxidants. “In a normal cell an antioxidant might be very good. But if you have a small tumor that might become a cancer, it will reduce p53 and the tumor will grow,” Bergö says.

A clinical researcher involved with the aborted trials that tested antioxidants to prevent lung and prostate cancersays he is “thrilled” by the study. “It’s the first paper I’ve seen that goes into some of the molecular biology to explain what we saw,” says medical oncologist Gary Goodman of the Swedish Cancer Institute in Seattle, Washington. “This really shows that high doses of vitamins can be harmful.”

Others are more restrained. “It’s a provocative study,” says cancer biologist David Tuveson of Cold Spring Harbor Laboratory in New York. “Perhaps we should look more carefully at what’s available over the counter.” But he would like to see a more detailed explanation of how the cell’s sensing of reactive species controls p53 activity. Lung disease researcher Shyam Biswal of Johns Hopkins University in Baltimore, Maryland, wonders if the results would be the same in mice with cancer sparked by a carcinogen, rather than an existing mutation. “The model is great, but it’s a very aggressive model,” Biswal says.

Another huge caveat, Kramer adds, is that in the earlier lung cancer prevention trials, only the participants taking β carotene had a higher risk of lung cancer, not those on vitamin E alone. “It’s not likely that all antioxidants are exactly the same,” he says. He and others also emphasize that the study does not suggest that people should eat less fruit and vegetables, which provide smaller doses of antioxidants and likely have other benefits.

Bergö and Lindahl now plan to extend their mouse studies to tests of β carotene and vitamin C and to other cancer types. They also plan to comb through medical records in Sweden to see if lung disease patients receiving NAC are at higher risk for lung cancer.

http://news.sciencemag.org/biology/2014/01/antioxidants-could-increase-cancer-rates

— Last Edited by Greentea at 2014-01-30 07:28:43 —