Marine-derived omega-3 fatty acids: fishing for clues for cancer prevention.

Omega-3 fatty acids (FA) are polyunsaturated essential FA with anti-inflammatory properties. The most potent are the marine-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which counteract the pro-inflammatory omega-6 FA. Americans take in an average of only 100 mg of EPA plus DHA per day resulting in a low omega-3:omega-6 intake ratio of 1:10 favoring inflammation. Cohort and/or case control studies suggest EPA and DHA are promising for breast, colon, and prostate cancer risk reduction. Mechanistic studies largely in preclinical models suggest EPA and DHA reduce synthesis of prostaglandin E2 and other inflammatory cytokines, decrease aromatase activity and proliferation, promote differentiation and apoptosis, and enhance insulin sensitivity. Animal models using 7% to 20% omega-3 added to chow are promising; however, this amount of omega-3 in a diet is unlikely to be acceptable to humans. The optimal EPA:DHA ratio or the lowest effective dose of EPA and DHA for cancer prevention is unclear, but it is likely to be more than 600 mg/day, which is six times the average American intake. Most phase II prevention trials use 1 to 3.3 g of EPA and DHA, which is safe and well tolerated. Two grams of EPA was associated with fewer polyps in individuals with familial adenomatous polyposis in a randomized, placebo-controlled trial. Identification of serum risk biomarkers modulated by EPA and DHA in healthy humans has remained elusive, but phase II prevention trials with tissue obtained for risk and response biomarkers are ongoing.