1. DiGiulio, Sarah

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Supplement use is common in the general population, as well as in people with chronic diseases and other illnesses, including cancer. But is there a possibility that dietary supplements could interact with cancer treatment? It's a question without a sufficient evidence-based answer, explained Christine Ambrosone, PhD, Professor of Oncology at Roswell Park Comprehensive Cancer Center. It's why she and her colleagues recently conducted a prospective study in patients with high-risk breast cancer to investigate the query. The data was published in the Journal of Clinical Oncology earlier this year (2020;38:804-814).

Christine Ambrosone,... - Click to enlarge in new windowChristine Ambrosone, PhD. Christine Ambrosone, PhD

"We found some support for the notion that use of dietary supplements during chemotherapy could have a negative impact on recurrence and overall survival," the authors note in the study.


Ambrosone and her colleagues conducted the prospective observational trial ancillary to a cooperative group trial led by SWOG. Women with "high risk" breast cancer were randomized to different dosing regimens of the same drugs. "Thus, we had large numbers of patients who were getting the same treatment agents," Ambrosone told Oncology Times.


When patients consented to the SWOG trial, they were given information about the ancillary supplement study and provided contact information if they wished to participate. Those who opted in answered questions about past and current supplement use before they started treatment on the trial. The individuals also answered survey questions after 6 months on the trial (at which point they should have completed treatment) to ask about the patients' supplement use during the trial.


"Thus, we had information for supplements on use before treatment (yes/no) and during treatment (yes/no) and we were able to look at combinations of usage," Ambrosone explained. She elaborated on what the data showed and its implications.


1 Why did you decide to do this research now?

"Actually, I began this area of research more than 20 years ago. I had been studying how genetic differences in metabolism of chemotherapy drugs could influence cancer outcomes (known as pharmacogenetics). In addition to studying differences in genes that metabolize chemotherapy agents, we also took a broader focus on generation of reactive oxygen species and oxidative stress, which is a primary mechanism of tumor cell kill with many chemotherapy drugs, including those used for breast cancer. Our research findings showed that genetic variants that resulted in higher levels of oxidative stress were associated with better outcomes among women getting treatment.


"This [finding] made me start thinking that, if oxidative stress generated by our bodies was useful in effective treatment, could taking antioxidant supplements possibly block these effects.


"When I started reading this literature, it was quite clear that there was no consensus, and virtually no empirical data upon which to base recommendations. However, because of the known mechanisms for tumor cell kill through oxidative stress, there were several recommendations in the literature for patients not to take antioxidant supplements during chemotherapy. Thus, I was motivated to fill this gap in knowledge.


"The topic is very important. In the general population and among cancer patients, supplement use is very common, and patients often take these supplements with hopes that they will aid in their fighting cancer. If these antioxidant supplements are actually weakening the effects of treatment, the medical and research community needs to be aware."


2 What would you say were the key findings from the research?

"In an earlier analysis where we looked at use of supplements in relation to chemotherapy-induced peripheral neuropathy, we found that there was reduced toxicity among women who used multivitamins before and during treatment. When we had adequate follow-up time, we analyzed data in relation to survival outcomes.


"Here we found that multivitamin use was not associated with recurrence or overall survival. However, there were relationships between use of specific supplements and both outcomes.


"Use of any antioxidant (C, E, A, carotenoids, co-enzyme Q10) was associated with higher risk of recurrence and mortality. We also found that use of iron supplements and use of vitamin B12 were also associated with poorer outcomes. In statistical analysis, we took into account other factors that could be affecting relationships, but the associations remained."


3 What's the bottom-line message that practicing oncologists and cancer care providers should know about your work? Should the findings change clinical practice?

"This is the first study conducted in the context of a rigorous clinical trial to look at use of supplements before and during chemotherapy. Although we did our best to take into consideration other factors that could be causing these relationships, we cannot rule out the possibility that there are other things that are actually driving these relationships. Furthermore, the relationships with antioxidants were of borderline significance (p=0.06). Thus, more studies need to be conducted that confirm the findings before clinical recommendations can be made.


"Although this study is not conclusive, the findings do suggest that it might not be beneficial for cancer patients to take supplements, particularly antioxidants, during chemotherapy. Patients should be counseled on maintaining a healthy diet, with recommendations to obtain maximal vitamins and minerals from foods, rather than from dietary supplements."