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BCRF Researcher Finds That Antioxidant Supplementation During Chemotherapy May Worsen Outcomes

Dr. Christine Ambrosone’s findings support a recommendation that breast cancer patients use caution when taking antioxidant supplements during treatment.

Studies have shown that the use of nutritional supplements, as well as other types of alternative therapy, has increased as patients seek less toxic and more holistic approaches to health. However, a new study conducted by BCRF investigator Christine Ambrosone, PhD, Professor and Chair of the Department of Cancer Prevention and Control at Roswell Park Comprehensive Cancer Center in Buffalo, NY, has revealed new evidence supporting recommendations against the use of one type of alternative therapy—antioxidant supplements—during chemotherapy.

Chemotherapy is a standard component of most cancer treatments and is very effective at killing cancer cells. A number of chemotherapy agents work through the generation of inflammatory molecules called reactive oxygen species (ROS) that are toxic to cells. Antioxidants reduce ROS, which is a good thing—but not when the goal is to kill cells. There has been concern that supplemental antioxidants, which patients may take for their purported health benefits, can counter the effect of chemotherapy by reducing ROS.

The study, called Diet, Exercise, Lifestyle and Cancer Prognosis (DELCaP), was conducted within a clinical trial led by SWOG Cancer Research Network (S0221) to compare chemotherapy dosing regimens in newly diagnosed patients with high-risk breast cancer. Patients received the same drugs but at different dosing regimens to see if one dosing schedule was more effective than the other.

Patients participating in the DELCaP study were asked to complete a questionnaire about supplement use, diet, exercise, and other lifestyle factors at the beginning of the study and after completion of chemotherapy. 1,600 patients were enrolled; the study, published in the Journal of Clinical Oncology, included 1,134 patients who completed both surveys.

The key findings: Continuous antioxidants use, but not multivitamin use, was associated with worse outcomes.

  • Patients who took supplemental antioxidant (vitamins, A, C, E, carotenoids, coenzyme Q) before and during chemotherapy had a 40 percent increase in the risk of experiencing a recurrence or death than those with less frequent antioxidant use.
  • Antioxidant use had no effect on outcomes when taken either before or only during chemotherapy. The continuous use seemed to be a factor in causing worse outcomes.
  • Multivitamin use did not affect outcomes and in some cases may have attenuated the adverse effect of antioxidants.
  • Supplemental vitamin B-12 and iron were strongly associated with disease progression and death.

Other studies have looked at supplement use and cancer outcomes, but none have studied supplement use specifically during chemotherapy. This is the first study to assess supplement use before, during, and after chemotherapy with a median follow-up of over 8 years. Another strength of Dr. Ambrosone’s study is that it was conducted in the context of a clinical trial where all patients received the same drugs.

The researchers were somewhat surprised by some of the findings. They hoped that a clinical trial of more than 3,000 patients would be an excellent opportunity to assess the effects of supplement use on patient outcomes. What they found, however, was that the number of patients taking antioxidants was much lower than trends would predict. This hampered their ability to assess the effects of individual antioxidants or to draw firm conclusions.

While there was not enough data to assess individual antioxidants, Dr. Ambrosone’s team found that supplemental vitamin B-12 before or during chemotherapy was strongly associated with worse outcome. The same was true for supplemental iron during chemotherapy.

What’s next? This study was observational in nature and was not designed to determine causation (whether supplement use is the reason some patients had worse outcomes). But it does support a recommendation of caution with supplements, particularly antioxidants, during chemotherapy. Dr. Ambrosone is collaborating with colleagues at Kaiser Permanente Northern California on a prospective study of more than 4,000 women with breast cancer, which collects data on habits at multiple timepoints. This large study may shed some additional light on the effects of dietary supplements on treatment outcomes.

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