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Patients with breast cancer who use supplements during chemotherapy may be at an increased risk of recurrence and death, a new study suggests.

Use of dietary supplements that boost levels of antioxidants, iron, vitamin B12 and omega-3 fatty acids appeared to lower the effectiveness of chemotherapy, researchers report in the Journal of Clinical Oncology.

"From this study and others in the literature, it seems that it may not be wise to take supplements during chemotherapy," said Christine Ambrosone, chair of cancer prevention and control, and senior vice president for population sciences at the Roswell Park Comprehensive Cancer Center in Buffalo, New York.

"It's thought that antioxidants might interfere with the ability of chemotherapy to kill cancer cells," Ambrosone explained. "One way chemotherapy works is by generating lots of oxidative stress. The thinking is that antioxidants may block oxidative stress and make chemotherapy less effective."

Doctors have been advising patients for a number of years not to take antioxidants during chemotherapy, Ambrosone said.

"But there was no strong empirical data for that recommendation," she added.

To take a closer look at whether supplement use might impact chemotherapy's effectiveness, Ambrosone and colleagues analyzed data from the Diet, Exercise, Lifestyle and Cancer Prognosis study, which was piggybacked onto a trial designed to determine the best dose and schedule of chemotherapy drugs.

Participants were queried about their use of supplements at the outset and during treatment, and about their lifestyle, diet and exercise habits.

The researchers focused on 1,134 patients who filled out the surveys and followed them for a median of six years. In this particular group of patients, supplement use was much lower than is typical, Ambrosone said, with 20% taking supplements prior to starting chemo and 13% during the treatments.

After accounting for other factors that might increase the risk of recurrence or death, they found patients who took any antioxidant at the outset and during chemotherapy — including carotenoids, Coenzyme Q10 and vitamins A, C, and E — were 41% more likely to have their breast cancer return and 40% more likely to die during follow-up compared to patients using no supplements.

The findings were similar for most individual antioxidants taken before and during chemo, particularly vitamin A. But for the others, the results were not statistically significant, meaning the differences were too small to rule out the possibility they were due to chance. Ambrosone attributes this to the small numbers of patients taking these supplements.

B12, iron

Those taking B12 and iron supplements were at greater risk of recurrence and those results were statistically significant.

Women taking B12 were 83% more likely to experience a recurrence and 22% more likely to die during follow-up compared to those who did not take those supplements. Women taking omega-3 supplements before and during chemo had a 67% higher likelihood of recurrence and those taking iron supplements were 79% more likely to experience a recurrence.

Previous research has suggested that iron "can play a role in both cancer initiation as well as promotion," Ambrosone said.

Dr. Amy Tiersten welcomed the new research.

"I am really happy to see that this study has been done," said Tiersten, a professor of medicine, oncology and hematology at the Icahn School of Medicine at Mount Sinai in New York City. "For years we have been cautioning patients about the use of vitamins, in particular anti-oxidants, during chemotherapy for breast cancer."

"There has been ongoing theoretical concern about the fact that while antioxidants may protect normal cells from the toxic effects of chemo, we don't know that they don't also protect the cancer cells," Tiersten said in an email. "Now we have solid data to back up that concern. I am a bit surprised by the magnitude of the effect, a 41% increase in the risk of recurrence for patients taking these supplements. I have always told patients on chemotherapy that the best way to get their vitamins is through a well-balanced diet, and will continue to do so given these data."