Dietary antioxidants during cancer chemotherapy: Impact on chemotherapeutic effectiveness and development of side effects

Several studies suggest that dietary supplementation with antioxidants can influence the response to chemotherapy as well as the development of adverse side effects that results from treatment with antineoplastic agents. Administration of antineoplastic agents results in oxidative stress, i.e., the production of free radicals and other reactive oxygen species (ROS). Oxidative stress reduces the rate of cell proliferation, and that occurring during chemotherapy may interfere with the cytotoxic effects of antineoplastic drugs, which depend on rapid proliferation of cancer cells for optimal activity. Antioxidants detoxify ROS and may enhance the anticancer effects of chemotherapy. For some supplements, activities beyond their antioxidant properties, such as inhibition of topoisomerase II or protein tyrosine kinases, may also contribute. ROS cause or contribute to certain side effects that are common to many anticancer drugs, such as gastrointestinal toxicity and mutagenesis. ROS also contribute to side effects that occur only with individual agents, such as doxorubicin-induced cardiotoxicity, cisplatin-induced nephrotoxicity, and bleomycin-induced pulmonary fibrosis. Antioxidants can reduce or prevent many of these side effects, and for some supplements the protective effect results from activities other than their antioxidant properties. Certain side effects, however, such as alopecia and myelosuppression, are not prevented by antioxidants, and agents that interfere with these side effects may also interfere with the anticancer effects of chemotherapy.