Some Supplement Use During Chemotherapy Negatively Impacts Survival Outcomes

Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221)

An article published on December 19, 2019 in the Journal of Clinical Oncology is making some waves due to it’s findings. The Diet, Exercise, Lifestyle and Cancer Prognosis (DELCaP) study asked the question: what effect do supplements, specifically antioxidant supplements have on survival outcomes in breast cancer patients undergoing chemotherapy? So lets dive into why this question is relevant.

The use of supplements in the United States is steadily increasing and some supplements have been found to have incredibly beneficial properties as far as maintaining proper nutrition, reducing risks of some chronic conditions, and alleviating symptoms and side effects of illnesses or medications. As in any other group, people with cancer are also using dietary supplements, some with the knowledge of their oncologists, and others on their own volition. There’s always a concern when someone on active cancer therapy is taking new medications, regardless of if the medication is prescribed, or over the counter simply because of the risk of interaction.

You may be asking, “why does it matter if someone on chemo is taking supplements”? Some cytotoxic medicines (i.e. chemotherapy) work by generating reactive oxygen species (ROS) and there’s concern that the use of dietary supplements, specifically those that act like anti-oxidants, actually reduce the efficacy of the chemotherapy. Generally, oncologists recommend that patients not take antioxidant supplements during chemotherapy.

In this study, breast cancer patients who were receiving treatment with chemotherapy (Cyclophosphamide, Doxorubicin, and Paclitaxel) were asked about their use of dietary supplements. In total, 1134 people being treated for breast cancer with the above chemotherapy were assessed both at the beginning of the study (registration) and during treatment.

• Who were the patients? —mostly women averaging 50 years old, with an average BMI of 30. These women were evenly distributed between pre- and post-menopausal. They were majority white, non-Hispanic, and most with greater than high school level of education.

• What was considered “regular use” of supplements?— people who used a supplement at least once a week before treatment.

• How did patients participate? — via a baseline questionnaire (Q1) before initiating chemotherapy and a follow up questionnaire (Q2) about 6 months after, when chemotherapy was near completion.

• Antioxidant supplements assessed in this study were Vitamin A, Vitamin C, Vitamin E, Carotenoids, Coenzyme Q10.

• Non-antioxidant supplements assessed in this study include vitamin B12 and iron.

The researchers found that 17.5% of patients used antioxidant containing supplements (see above) during chemotherapy and 44% of patients took multivitamins during chemotherapy. They found that patients who used any antioxidant both before and during chemotherapy had an increased risk of disease recurrence, and to a lesser extent, death. Additionally, there was “no relationship with outcomes for use of antioxidants only before treatment initiation or only during chemotherapy”. Specifically, there was a relationship noted with the use of vitamin A and carotenoid supplements and increased disease recurrence and death. Multivitamin use at any point in time did not negatively or positively affect survival outcomes. The use of vitamin B12 and iron supplements before and during treatment was associated with poorer disease-free survival and overall survival. The use of omega-3 fatty acids before and during treatment was associated with some disease-free survival but not overall survival.

The researchers stated, “ we found some support for the notion that use of dietary supplements during chemotherapy could have a negative impact on recurrence and overall survival”. They found that people taking antioxidant supplements before and during chemotherapy had a 41% hazard of recurrence of the disease and conclude that “these findings of increased risk of poor outcomes with use of antioxidant supplements are congruent with concerns that use of antioxidants during chemotherapy could reduce the cytotoxic effects of ROS (reactive oxygen species) generated by numerous chemotherapy agents”. Stated simply: chemotherapy creates a reaction to kill cancer cells, but antioxidants quench the reaction and the cancer cells continue to thrive.

There are many potential confounding aspects to this study, but a couple of things I wanted to point out are:

Most patients who completed the questionnaire process were those who tended to have more toxicity either from disease or treatment. For example, if you are doing well with limited side effects you likely wouldn’t spend your time filling out a questionnaire, but if you have concerns, you tend to look for a way to voice that concern, and thus are more likely to fill out the questionnaire. If a majority of patients completing the survey are already sicker, this could have skewed the findings.

The negative effects of iron could be due to the fact that iron allows for the production ROS which in turn can help tumors grow by contributing to malignant transformation. Also, the researchers postulate that people requiring supplementation with iron tend to do so in order to treat iron deficiency anemia, and an existing condition of anemia in and of itself could be related to breast cancer recurrence.

In general, patients whose breast cancer returned were likely to have a higher BMI, be older, and postmenopausal. They also tended to have more high risk features such as triple negative breast cancer, or greater than 4 positive lymph nodes.

So you may be wondering:

• Should you stop taking supplements? Based on this paper, I say if you’re about to start treatment with chemotherapy or are already on chemotherapy, err on the side of caution and stop taking supplements and discuss things with your oncologist right away.

• Should you stop taking multivitamins? No need. There was no correlation of harm or benefit with multivitamin use while receiving chemotherapy. In fact, the study does show that “there was reduced risk of chemotherapy induced peripheral neuropathy with use of multivitamins before diagnosis and, to a lesser extent, during chemotherapy”.

Do not be disheartened if you take supplements. This study isn’t saying that general use of supplements is bad. It’s saying that because of the anti-oxidant properties in some supplements, they should not be taken while on chemotherapy as they could interrupt the work of the chemotherapy, which can lead to disease recurrence or even death from disease progression.

Research into the topic of supplements and antioxidants is ongoing so always keep your doctor informed about what you take,