Effects of cotreatment with omega-3 polyunsaturated fatty acids and anticancer agents on oxidative stress parameters: a systematic review of in vitro, animal, and human studies.

Context: Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid and eicosapentaenoic acid, demonstrate possible beneficial effects as adjuvants in cancer treatment. One mechanism seems to be related to alterations in the redox status of cancer cells. Such alterations are thought to act in synergy with conventional anticancer agents. Objective: This review examines published data on the effects of cotreatment with anticancer agents and n-3 PUFAS on oxidative stress parameters to determine whether any patterns of oxidative stress alterations can be identified. Data Sources: A systematic search of MEDLINE (via PubMed) was conducted to identify articles published in English, Spanish, or Portuguese until November 2017. Study Selection: The following inclusion criteria were applied: (1) individuals or animals with cancer or malignant cell lines supplemented with some source of n-3 PUFAs; (2) concomitant use of anticancer treatment; and (3) evaluation of oxidative stress-related variables. Data Extraction: A standardized outline was used to extract the following data: study type, supplement used, type of cells, tumor or patient characteristics, study design, anticancer treatment used, and oxidative stress-related outcomes. Results: After the literature search and screening of 1563 citations, 28 studies were included for data extraction and evaluation: 16 in vitro studies (2 of which also used in vivo studies), 8 animal studies, and 4 human studies (3 clinical trials and 1 case series). In most in vitro and animal studies, intervention groups receiving cotreatment with n-3 PUFAs showed enhanced lipid peroxidation and cytotoxicity compared with groups receiving anticancer treatment alone. Eleven of the 12 studies that investigated the effect of vitamin E on the sensitivity of cancer cells to the oxidative stress caused by n-3 PUFAs showed that vitamin E abolished the positive effects of cotreatment. Conclusions: Alterations in oxidative stress caused by cotreatment with anticancer agents and n-3 PUFAs can exert positive effects on the efficacy of conventional treatment. This seems to occur in most cells and tumors tested thus far, but not all. Identifying tumors that are sensitive to these oxidative effects may provide support for the rational use of n-3 PUFAs as an adjuvant treatment in specific types of cancer.