ANTIOXIDANTS ARE SUBSTANCES that help protect cells from free radicals—chemicals that damage cells in ways that can increase cancer risk. The body naturally makes some of the antioxidants needed to control free radicals. Other antioxidants are found in foods like fruits, grains, vegetables, nuts and seeds.

Antioxidants can also be obtained through dietary supplements. These supplements, such as vitamins C, A and E, carotenoids, and coenzyme Q10, are often marketed as immune-system boosters and free-radical fighters that can help reduce risk of cancer and other diseases. Their sales are flourishing. Worldwide antioxidant sales are expected to reach more than $4.5 trillion by 2022. Because of this widespread use, some people newly diagnosed with cancer are likely to be taking antioxidant supplements. Others may start taking them after diagnosis, viewing them as a way to help their immune system fight cancer.

Christine Ambrosone, a molecular epidemiologist at Roswell Park Comprehensive Cancer Center in Buffalo, New York, studies genetic and nongenetic factors that may increase cancer risk or affect how cancer patients respond to treatments. She recently led a study that looked at supplement use among breast cancer patients being treated in a clinical trial. The research, published in the March 2020 Journal of Clinical Oncology, found the use of an antioxidant supplement was associated with an increased risk of cancer recurrence or death.

Ambrosone spoke with Cancer Today about her study and what cancer patients should know about dietary supplements.

CT: Why did you decide to do this study?
Ambrosone: Over the years, there has been controversy about whether or not it is OK for patients to take dietary supplements during chemotherapy. A specific area of concern has been supplements that contain antioxidants. Some types of chemotherapy and radiation kill tumor cells by generating a lot of oxidative stress. The thinking has been that antioxidants could block this effect, but there was no empirical data to know if this was true. 

CT: How was this study conducted?
Ambrosone: The SWOG Cancer Research Network was launching a clinical trial that would randomize breast cancer patients to different dosing regimens of the same drugs. I was the SWOG co-chair of molecular epidemiology and worked with clinical trial investigators to integrate our study into theirs. The patient consent form explained that because we don’t know if what you do during chemotherapy will affect treatment outcomes, we would be asking patients about their lifestyle. All of the patients got a questionnaire when they started the study asking about what they were doing before their diagnosis. They answered another questionnaire when they completed treatment about what they did during treatment. The questions weren’t only about supplements. We also asked about physical activity, alcohol use and smoking.

CT: What did you learn?
Ambrosone: When we looked at antioxidants as a category, we saw an association that had borderline significance between their use and increased risk of recurrence and death.

CT: How does this add to what we know?
Ambrosone: Researchers started studying dietary supplements because certain foods were associated with better health, and epidemiologic studies found a strong relationship between certain fruits and vegetables and a reduced cancer risk. So, researchers began two clinical trials to see if beta carotene and vitamin A reduced lung cancer risk in high-risk patients. Both studies had to be stopped when the data showed the patients on the supplements had an increased risk of being diagnosed with lung cancer. I think this drives home the point that you should really try to eat a healthy diet, because when you pull just one nutrient out of fruits and vegetables, you don’t know how it’s going to work all by itself.

CT: Should oncologists tell patients not to take supplements?
Ambrosone: We are cautious in our paper about whether or not these results should be acted upon in terms of how a doctor advises a patient. There are reports that 50% to 60% of breast cancer patients take dietary supplements, often at high doses. Because we had more than 1,000 women in this study, we thought we would be able to answer the question about harm, but not that many of the women in our study were actually taking supplements during chemotherapy, which affected the strength of our analysis. 

CT: Should there be a randomized trial of supplements in cancer patients?
Ambrosone: There is no reason to do a randomized trial. There is no evidence they are beneficial. Ethically, we could not do it because we do have evidence that people who take supplements could have worse outcomes.

This interview has been edited and condensed for clarity.