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Research Update — May 2021

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Ambrosone, C.B., Zirpoli, G.R., Hutson, A.D, et al.
Dietary supplement use during chemotherapy and survival outcomes of patients with breast cancer enrolled in a cooperative group clinical trial (SWOG S0221)
Journal of Clinical Oncology (2019), 38:804-814.


Purpose: Despite reported widespread use of dietary supplements during cancer treatment, few empirical data, with regard to their safety or efficacy, exists. Because of concerns that some supplements, particularly antioxidants, could reduce the cytotoxicity of chemotherapy, we conducted a prospective study ancillary to a therapeutic trial to evaluate associations between supplement use and breast cancer outcomes.

Methods: Patients with breast cancer randomly assigned to an intergroup metronomic trial of cyclophosphamide, doxorubicin, and paclitaxel were queried on their use of supplements at registration and during treatment (n =1,134). Cox proportional hazards regression adjusting for clinical and lifestyle variables were used. Recurrence and survival were indexed at 6 months after enrolment using a landmark approach.

Results: There were indications that use of any antioxidant supplement (vitamins A, C, and E; carotenoids; coenzyme Q10) both before and during treatment were associated with an increased hazard of recurrence (adjusted hazard ratio [adjHR], 1.41; 95% CI, 0.98 to 2.04; P = .06) and, to a lesser extent, death (adjHR, 1.40; 95% CI, 0.90 to 2.18; P = .14). Relationships with individual antioxidants were weaker, perhaps because of small numbers. For non-antioxidants, vitamin B12 use, before and during chemotherapy, was significantly associated with poorer disease-free survival (adjHR, 1.83; 95% CI, 1.15 to 2.92; P< .01) and overall survival (adjHR, 2.04; 95% CI, 1.22 to 3.40; P< .01). Use of iron during chemotherapy was significantly associated with recurrence (adjHR, 1.79; 95% CI, 1.20 to 2.67; P< .01) as was use before and during treatment (adjHR, 1.91; 95% CI, 0.98 to 3.70; P = .06). Results were similar for overall survival. Multivitamin use was not associated with survival outcomes.

Conclusion: Associations between survival outcomes and use of antioxidant and other dietary supplements, before and during chemotherapy, were consistent with recommendations for caution among patients when considering the use of supplements, other than a multivitamin, during chemotherapy.


Use of dietary supplements including antioxidant supplements is very common in the general population. Antioxidant supplements include vitamins C/E, selenium, beta-carotene, co-enzyme Q10, alpha-lipoic acid, among many others. However, whether or not antioxidant supplement use during cancer treatment is beneficial or harmful remains unclear. Cancer treatment with chemotherapy and radiation therapy works in part because of the generation of reactive oxygen species (ROS) to oxidate cancer cells. On the other hand, these ROS can also damage healthy tissue. Whether antioxidant use mostly reduces treatment effectiveness or mostly reduces treatment-related adverse effects (e.g., peripheral neuropathy) remains unknown.

The authors of this study designed a prospective observational study among over 1,000 women undergoing standard chemotherapy for breast cancer. They asked the women about supplement use at the beginning of and during treatment and then followed them for about eight years to track the incidence of both cancer recurrence and mortality. Statistical analyses were used to ensure confounding variables (e.g., estrogen/progesterone/HER2 receptor status, lymph node involvement, body mass index, alcohol/tobacco use, and physical activity) were controlled.

Results indicated that patients who used antioxidant supplements before and during chemotherapy had a 41% and 40% increase in hazard of cancer recurrence and death, respectively. Use of a multivitamin or vitamin D at any time was not associated with survival outcomes. Use of other common non-antioxidant supplements such as B12, omega-3 fatty acids, and iron were also associated with poorer outcomes.

This was an observational study so the design and results were more prone to biases which may have limited the weight of the results. Nonetheless, it was well-designed and executed. The results do support the generally accepted current recommendations to avoid antioxidant supplement use during cancer treatment.

Overall, it is probably best to consume antioxidants in whole food form. For example, previous studies have shown that increased omega-3 fatty acid consumption from fish is associated with benefit in cancer patients. A diet rich in antioxidants is tasty and doable and provides all the nutrients in proper combinations. InspireHealth’s medical doctors and dietitians are pleased to meet with you to review your questions about nutritional supplements.