The core intervention of interest is antioxidant dietary supplements concomitant with chemotherapy, radiotherapy or other biological therapy for cancer. We are defining antioxidant dietary supplements as orally consumed products with known ability to prevent cellular damage by reacting with oxidising free radicals.40 Antioxidant dietary supplements cover a wide range of substances, including vitamins (eg, vitamin C), minerals (eg, selenium), amino acids (eg, n-acetylcysteine), carotenoids (eg, lycopene), botanicals (eg, polyphenols), and hormones (eg, melatonin). Studies involving intravenous administration of antioxidants in a medical setting (eg, intravenous vitamin C) will be excluded from this scoping review. Oral and intravenous antioxidants are not only processed differently by the body but oral supplements may be taken by patients without direct assistance of medical professionals, and thus, have different clinical and public health implications. Studies involving mushrooms and mushroom products will be excluded because their mechanism is primarily through immunomodulation.41 Studies involving compound herbal formulas will also be excluded due to the potential for multiple mechanisms of activity that confound the research question. Finally, although many foods such as fruits and vegetables are good sources of antioxidants, whole food dietary interventions (eg, changes in food habits) will also be excluded from this scoping review due to the potential for confounding by non-antioxidant dietary components with known activity against cancer (eg, histone deacetylase-inhibition, DNA methylation).42 43

The core outcomes of interest will consist of (1) therapeutic response to treatment with chemotherapy, radiotherapy or other biological therapy, (2) improvements in chemotherapy-related side effects and quality of life and (3) increases in adverse effects potentially related to antioxidant supplementation. Response to treatment may be measured as mortality or with indicators of morbidity (eg, cancer progression, recurrence). Because it may not be possible to establish whether side effects and other adverse events are more likely related to the cancer treatment or to the supplement use, we will document when adverse events are presented within the reviews as side effects due to either cancer treatment or supplement use, but we will discuss the findings both separately and jointly. We will include outcomes measured at any time point.

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