Increased intake of omega-3 fatty acids, which is widely promoted as a way to prevent cardiovascular disease and cancer, may increase the risk of prostate cancer (PCa), especially aggressive disease, according to a study that confirms the findings of previous investigations.

Theodore M. Brasky, PhD, of the Ohio State University Comprehensive Cancer Center in Columbus, and colleagues studied 2,198 men enrolled in the SELECT (Selenium and Vitamin E Cancer Prevention Trial). Of these, 834 were diagnosed with PCa (156 with high-grade disease) and 1,364 were not. Compared with men in the lowest quartile of total long-chain omega-3 fatty acids, those in the highest quartile had a 44% and 71% increased risk of low- and high-grade disease, respectively, and a 43% increased risk of any PCa, Dr. Brasky’s team reported online in the Journal of the National Cancer Institute.

The researchers calculated the total long-chain omega-3 fatty acid level as the sum of eicosapentaenoic (EPA), dodosapentaenoic (DPA), and docosahexaenoic acids (DHA), which are derived from oily fish and fish oil supplements. High levels of each of these fatty acids were associated with an increased PCa risk. High levels of EPA were associated with an increased risk of low-grade PCa. High levels of DPA and DHA were associated with an increased risk of low-grade and total PCa.

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The new findings corroborate those of a study published in the American Journal of Epidemiology by Dr. Brasky and colleagues in 2011. That study examined data from men enrolled in the Prostate Cancer Prevention Trial. Compared with men in the lowest quartile of serum DHA, those in the highest quartile had a 2.5 times increased risk of high-grade PCa. The study also found that high serum levels of trans-fatty acids were associated with a decreased risk of high-grade disease.

The researchers said it is unclear from the present study why high levels of long-chain omega-3 fatty acids would increase PCa, but the replication of this finding in two large studies indicates the need for further research into possible mechanisms. One potentially harmful effect of omega-3 fatty acids is their conversion into compounds that can cause damage to cells and DNA, and their role in immunosuppression.

The SELECT trial enrolled 35,533 men who were randomly assigned to take vitamin E alone, selenium alone, and vitamin E in combination with selenium. Results showed that men who took vitamin E alone had a significant 17% increased risk of PCa compared with placebo recipients after a total follow-up of seven years. Men who took both vitamin E and selenium did not have an increased risk.