Antioxidants speed lung cancer growth in mice, study finds

by Kerry Sheridan
Antioxidants are chemical compounds that delay some types of cell damage. Well-known antioxidants include vitamin A, C (pictured here), and E, as well as some medications. Credit: Bickel/Science Translational Medicine

People who smoke or have lung cancer should think twice about taking vitamin supplements, according to a Swedish study Wednesday that showed certain antioxidants may make tumors grow faster.

Lab mice that already had were given vitamin E and a drug called acetylcysteine, which sped the growth of their tumors and made them die faster than mice that did not ingest supplements.

"Antioxidants caused a three-fold increase in the number of tumors and also aggressiveness, and the antioxidants caused the mice to die twice as fast," said study author Martin Bergo of the University of Gothenburg in Sweden.

"If we gave a low dose, tumors increased a little bit. And if we gave a high dose, tumors increased a lot."

Research on human growing in a lab dish also showed that the antioxidants caused the cells to multiply faster than they would have alone, suggesting the same might happen in human patients.

While more work needs to be done to confirm the effect in people, Bergo urged those with lung cancer, chronic obstructive pulmonary disease and smokers to take caution.

"You can walk around with an undiagnosed lung tumor for a long time," he said.

"If you are in this patient group, then taking extra antioxidants might be harmful and it could speed up the growth of that tumor."

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Antioxidants are chemical compounds that delay some types of cell damage. Well-known antioxidants include vitamin A, C (pictured here), and E, as well as some medications. Credit: Bickel/Science Translational Medicine

Mixed results from supplement studies

The body produces its own antioxidants to prevent DNA damage from chemicals known as , but needs more from healthy foods like leafy greens, vegetables and fruits to stay healthy.

However, a large body of research on in humans has returned mixed results.

Some studies have suggested that people who take antioxidant supplements actually face a higher risk of cancer than those who do not.

One such study of nearly 30,000 men in Finland, which concluded in 1993, found that smokers who took the antioxidant beta carotene had a higher rate of cancer and greater risk of dying.

Other studies, such as the SELECT trial which enrolled 35,000 US and Canadian men beginning in 2001, found that men who took vitamin E were more likely to get prostate cancer.

"We haven't completely ironed out which vitamins, if any, may prevent cancer and which may cause cancer development or growth," said Benjamin Levy, director of thoracic medical oncology at Mount Sinai Beth Israel Hospital in New York.

"This study may help explain the negative findings from prior clinical studies, including the ATBC and SELECT studies," said Levy, who was not involved in the research.

Antioxidants protect tumors, too

Researchers said their findings suggest antioxidants help tumors cut down on , just as they do in normal cells, allowing the tumors to grow faster.

Free radicals can damage cells and possibly lead to cancer. But free radicals exist in , too, explained Bergo.

"So it is also in the tumor's interest to suppress free radicals, and that is what we are doing when we take extra antioxidants—or give it to the mice in this case," he told reporters.

A protein called p53 can sense when DNA has been damaged by the buildup of molecules called reactive oxygen species (ROS).

P53 can stop the growth of the cell and thereby stop the cancer.

When extra antioxidants reduce the level of ROS, this "allows the cancer cells to escape their own defense system," said co-author Per Lindahl from the University of Gothenburg.

Of particular concern is the finding that acetylcysteine increased tumor growth, since the drug is often given to patients with chronic obstructive pulmonary disease (COPD) as a way to help them breathe better and clear mucus from their lungs.

"We think that the use of acetylcysteine in this patient group should probably be carefully evaluated," said Bergo.

He added that researchers are now combing through data registries to find out if COPD patients—including people with chronic bronchitis and emphysema—have higher cancer rates after taking the drug.

The research appears in the journal Science Translational Medicine.

More information: "Antioxidants Accelerate Lung Cancer Progression in Mice," by V.I. Sayin et al. Science Translational Medicine, 2014.

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SusejDog
not rated yet Jan 29, 2014
This applies only to people with existing cancerous tumors, not so much to ones without tumors.

One problem with studies of vitamin E and beta carotene is that they use non-natural stereoisomers. You ideally only want to supplement natural stereoisomers and in a balanced form, providing mixed tocopherols and mixed carotenes.

The other rational thing to do here is to find p53 based tumor suppressors.
Skepticus_Rex
not rated yet Jan 29, 2014
What next needs to be done as a follow-up study is to record whether there is any difference in response of the tumors to l-alpha-tocopherol, d-alpha-tocopherol, and dl-alpha-tocopherol (the latter being what is found in most vitamin supplements on the market). The same goes for differences of chirality in beta carotene as well.
SusejDog
not rated yet Jan 30, 2014
Hi Skepticus_Rex, I find it somewhat wasteful to prioritize the study of unnatural isomers. The only natural form is "mixed" (all four) d- tocopherols in optimal ratios, and so the priority should first lie here. Similarly with the carotenes. Once this is done, then we can afford to be nerdy about it and compare the d-, l-, and dl- with each other.

Regardless, I believe in the spirit of the study that powerful antioxidants can protect tumor cells just as well if not better than they can protect normal cells. To me, it just means I need to also work on separately promoting my tumor suppression pathways, but how?
Shakescene21
1 / 5 (1) Feb 01, 2014
I wonder about the scientific validity of a study that tests two chemicals at once instead of testing each one separately. How does a study conclude that Vitamin E is increasing cancer when the mice are also being fed large doses of acetylcystiene?

Regarding acetylcystiene, this is a drug that is used as a mucous thinner, and I don't think it is used as a nutritional supplement.
Skepticus_Rex
not rated yet Feb 03, 2014
Hi Skepticus_Rex, I find it somewhat wasteful to prioritize the study of unnatural isomers. The only natural form is "mixed" (all four) d- tocopherols in optimal ratios, and so the priority should first lie here. Similarly with the carotenes. Once this is done, then we can afford to be nerdy about it and compare the d-, l-, and dl- with each other.

Regardless, I believe in the spirit of the study that powerful antioxidants can protect tumor cells just as well if not better than they can protect normal cells. To me, it just means I need to also work on separately promoting my tumor suppression pathways, but how?


The d- and l- refer to the stereomers of the molecules, as in chirality. Differences in chirality in the stereomers of molecules can make differences in usefulness as well as toxicity of substances. I am aware of the blend of tocopherols that occurs in nature. I am interested in the difference of use in the body and whether that has biochemical influence on cancers.