Fish oil is a dietary supplement that contains omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), though in doses that vary widely among brands.1 Omenga-3 fatty acids are components of cell membrane phospholipids, can provide energy, and are also used to produce eicosanoids, which are important signaling molecules.

Fish oil is a very popular supplement, with its use estimated among 7.8% of adults and 1.1% of children in the United States during a given 30-day period.2 Research has evaluated the role of fish oil to reduce cancer incidence and improve cancer outcomes by preventing toxicity or treating cancer- or treatment-associated side effects.

Cancer Incidence

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A meta-analysis of 19 randomized controlled trials (RCTs) that included 68,954 patients with at least 6 months follow-up demonstrated no effect of omega-3 fatty acid supplementation on overall cancer incidence (relative risk [RR], 1.10; 95% CI, 0.97-1.24; P = .12) or nonvascular mortality (RR, 1.00; 95% CI, 0.93-1.08; P = 1.00) compared with placebo.3 Similarly, a case-control study of patients with cardiovascular disease found no association between omega-3 fatty acid supplementation and development of cancer (hazard ratio [HR], 1.17; 95% CI, 0.87-1.58) or cancer-related mortality (HR, 1.47; 95% CI, 0.87-2.48).4

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Anticancer Treatment: Outcomes and Quality of Life

Multiple trials demonstrated that fish oil supplementation can improve outcomes during or after cancer treatment, such as improved response rate, increased function, and improved quality of life.

Improvement With Systemic Anticancer Treatment

A small RCT of 46 patients with non–small cell lung cancer (NSCLC) received fish oil (2.5 g EPA and DHA) in addition to the standard of care (SOC) chemotherapy (carboplatin with vinorelbine or gemcitabine).5 Adding fish oil resulted in a greater response rate at 60% compared with 25.8% with the SOC (P = .008). Clinical benefit was also greater in the fish oil group compared with the SOC group (80% vs 41.9%; P = .02). Overall survival at 1 year trended toward improvement with fish oil compared with SOC (60% vs 38.7%; P = .15), but was not significant. Dose-limiting toxicities were similar between groups.

Another RCT supplemented patients with colorectal cancer with 2 g fish oil (0.6 g EP and DHA daily) daily for 9 weeks. The supplemented group demonstrated a significantly prolonged time to tumor progression (593 vs 330 days; P = .04) compared with the control group.6 There was, however, no difference in the number of chemotherapy cycles, delays or interruptions, hospitalization, or days until death or progression, and 3-year survival.

Another RCT of 61 patients with esophageal cancer undergoing neoadjuvant chemotherapy found that omega-3 fatty acid–rich enteral nutrition resulted in less stomatitis (P = .018), aspartate aminotransferase elevation (P = .012), and alanine aminotransferase elevation (P = .015) compared with omega-3 fatty acid–poor enteral nutrition.7 Grade 3/4 diarrhea occurred less frequently with fish oil, but the difference was not significant and there was no difference in grade 3/4 leukopenia or neutropenia.

A study of 41 patients receiving paclitaxel demonstrated that omega-3 fatty acid supplementation reduced peripheral neuropathy (odds ratio, 0.3; 95% CI, 0.10-0.88; P = .029).8 Another study of 70 pediatric patients with acute lymphoblastic leukemia found that omega-3 fatty acid supplementation (1000 mg/d) reduced methotrexate-induced hepatotoxicity, as indicated by biomarkers of liver toxicity.9

Another study, which evaluated 249 women taking an aromatase inhibitor for breast cancer treatment, found no difference in aromatase inhibitor–associated arthralgia with omega-3 fatty acids (3.3 g per day) or placebo.10