Using Antioxidants and Other Supplements With Chemotherapy May Increase Risk of Breast Cancer Recurrence and Mortality

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Using antioxidants and other dietary supplements before and during adjuvant chemotherapy for breast cancer may increase the risk of recurrence and “to a lesser extent, death,” according to an analysis of dietary and nutritional data from a phase III trial, published in the Journal of Clinical Oncology.1

I have always been against the use of extra supplements during cancer treatment because there is literature for this.
— Kathy S. Albain, MD, FACP, FASCO

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With results including a 41% increase in risk of recurrence with supplement use, “you have to conclude that it is probably not beneficial to take supplements if you are otherwise taking in a good diet, and that furthermore, you may cause harm, in the sense that your treatment is going to be less effective,” Kathy S. Albain, MD, FACP, FASCO, a senior author of the study, said in an interview with The ASCO Post. Dr. Albain is Professor of Medicine, Division of Hematology/Oncology, Loyola University, Chicago Stritch School of Medicine, and Huizenga Family Endowed Chair in Oncology Research, Cardinal Bernardin Cancer Center, Loyola University Medical Center.

‘Compelling’ Data 

Part of the SWOG S0221 trial, the Diet, Exercise, Lifestyle, and Cancer Prognosis (DELCaP) study, randomly assigned patients with breast cancer to different treatment schedules with doxorubicin, cyclophosphamide, and paclitaxel and questioned them about regular use (at least once per week) of supplements at randomization and during chemotherapy. A total of 1,134 patients completed both questionnaires, with 18% reporting the use of at least one antioxidant daily and 44% taking multivitamins.

“The prevalence of supplement use, particularly antioxidants, was low compared with reports in the literature of use by patients with cancer and tended to decrease during treatment,” the authors noted. Recurrences numbered 251, and deaths, 181.

“When we considered the use of any antioxidant (vitamins C, A, and E; carotenoids; and coenzyme Q10), there was a 41% increase in hazard of recurrence with use both before and during treatment of borderline significance, with a similar but weaker association with mortality,” the authors wrote. Adjusted hazard ratios (HRs) were 1.41 (95% confidence interval [CI] = 0.98–2.04, P = .06) for recurrence and 1.40 (95% CI = 0.90–2.18, P = .14) for mortality.

“These data are fairly compelling for this type of study. It was prospective and observational and the first of its kind in breast cancer,” Dr. Albain pointed out.

‘Striking Associations’

The associations of antioxidant supplements with an increased risk of cancer recurrence and deaths were found only when the supplements were used both before and during chemotherapy, but not when the supplements were used only before or only during chemotherapy. Associations for most individual antioxidants were not statistically significant.

Among nonantioxidants, “Striking associations were found between treatment outcomes and vitamin B12 and iron supplements,” the researchers reported. Used before and during treatment, B12 was associated with reduced disease-free survival (HR = 1.83, 95% CI = 1.15–2.92) and overall survival (HR = 2.04, 95% CI = 1.22–3.40), and iron supplements were associated with greater recurrence (HR = 1.91, 95% CI = 0.98–3.70). The use of omega-3 fatty acids both before and during treatment was associated with disease-free survival (HR = 1.67; 95% CI = 1.12–2.49) but not overall survival.

Multivitamins Okay

“Patients taking multivitamins showed no signs of poorer or better outcomes after chemotherapy,” according to a SWOG news release about the study.2 This finding was “consistent with the only other study of lifestyle factors embedded in a clinical trial for colon cancer, CALGB 89803,” the researchers reported. That study had concluded, “Multivitamin use during and after adjuvant chemotherapy was not significantly associated with improved outcomes in patients with stage III colon cancer.”3

The finding that multivitamin use was not associated with survival outcomes may be due to reduced amounts of individual vitamins, such as A, C, and E, included in multivitamins, as compared to individual supplements. “Some of these individual supplements that were taken in the study were over and above what our bodies are intended to get,” Dr. Albain said.

Food Favored

Patients who are eating well before and during chemotherapy generally do not need a multivitamin. “It is not going to be absorbed if they don’t need it. It is not useful to them,” Dr. Albain noted.

“I tell patients that you can’t say enough for a well-balanced, careful diet—fruits and vegetables, whole grains—during your cancer treatment,” she explained. “There are many patients who can’t do that. Then you work with your dietitian. You try to get the nutrients into their diet by other ways. I do not tell them to take supplements over and above a multiple vitamin, which appears to be safe in this study.”

Patients who do take multivitamins because they are having trouble maintaining adequate nutrition during treatment should be advised to use those with levels of vitamins closest to the body’s physiologic needs, Dr. Albain added.

Persistent Issue

The study report noted that the “use of dietary supplements after a cancer diagnosis is common, [despite] concern that use of dietary supplements during treatment, particularly antioxidants, could reduce treatment efficacy [and] clinical recommendations that patients not take antioxidant supplements during chemotherapy.” So, why do many people start or continue to take supplements after a cancer diagnosis?

Dr. Albain said that a major reason is the desire and/or need to personally take action. “It is almost universal that a patient meeting me for the first time with a new diagnosis of cancer, will say, ‘Doctor, what can I do while you are doing what you are doing?’” In addition, well-meaning friends and family members may suggest that patients take a supplement that worked or seemed to work for them or others, or that they read about on the Internet.

“Patients may take supplements in an effort to do whatever they can to prevent their cancer from returning and/or to treat it when it is more advanced,” Dr. Albain said. But “by taking dietary supplements with a curative-intent chemotherapy regimen in the adjuvant setting for breast cancer, you are abrogating some of the benefits of the chemotherapy,” she stressed. “That is the important message.”

Although the study received coverage by medical and national media, the intense news cycle at the time the study report was issued may have prevented the message about the increased risk of breast cancer recurrence and mortality being more widely reported. “I am telling all of my patients about it,” Dr. Albain stated. “I have always been against the use of extra supplements during cancer treatment because there is literature for this.” She noted that the current study was conducted “in a very controlled fashion, with carefully administered questionnaires and extremely valid data.”

Existing Conditions

Habitual use of vitamin B12, iron, and antioxidants before and during chemotherapy “could be due to indication, with patients using these supplements to treat an existing condition such as anemia, which could, of itself, be related to breast cancer recurrence and death,” the researchers wrote.

Dr. Albain made it clear that “patients who are taking supplements for medical reasons—that is not the population we are speaking to. We would not want to alarm them. If they have a disorder for which they need to take B12 (one of the hematologic disorders, for example), they shouldn’t stop doing that.” But just to start taking supplements when breast cancer is diagnosed “is not a good idea,” she emphasized.

Widely Applicable?

As part of the SWOG S0221 trial, patients were randomly assigned to different treatment schedules with doxorubicin, cyclophosphamide, and paclitaxel for high-risk early breast cancer. The findings from this study about the use of dietary supplements are generally “applicable to this class of drugs—the anthracyclines, the cyclophosphamides, and the taxanes, which are the top three chemotherapeutic agents in breast cancer,” Dr. Albain asserted.

“These agents work by generating this oxidative stress,” she explained, and the trial results could probably be extrapolated to a different drug that works in that way. “But certainly, this applies broadly to standard chemotherapy regimens for breast cancer, and not just the way they were tested in this trial.” 

DISCLOSURE: Dr. Albain has served in a consulting or advisory role for Agendia, Genentech/Roche, Genomic Health, Myriad Genetics, Novartis, and Pfizer; has received research funding from Seattle Genetics; has received institutional research funding from Seattle Genetics; and has had other relationships with Puma Biotechnology.


1. Ambrosone CB, Zirpoli GR, Hutson AD, et al: Dietary supplement use during chemotherapy and survival outcomes of patients with breast cancer enrolled in a cooperative group clinical trial (SWOG S0221). J Clin Oncol. December 19, 2019 (early release online).

2. SWOG Cancer Research Network: Antioxidant use during chemo risky. December 19, 2019. Available at Accessed February 11, 2020.

3. Ng K, Meyerhardt JA, Chan JA, et al: Multivitamin use is not associated with cancer recurrence or survival in patients with stage III colon cancer: Findings from CALGB 89803. J Clin Oncol 28:4354-4363, 2010.

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