The fish vs. the prostate: Omega-3 fatty acids and the risk for prostate cancer

For the past 2 weeks, the most common question I have been getting from my male patients is whether they should continue with their fish oil, given the recent study linking fish oil with prostate cancer.

We have evidence that omega-3s decrease inflammation, and everyone presumed there would eventually be some data to support that omega-3s would reduce the risk for cancer. However, the study showed that men who had high blood concentrations of long-chain omega-3 polyunsaturated fatty acids (PUFA) had a 43% increase in the risk for all grades of prostate cancer, as compared with men who had the lowest concentrations. The risk for high-grade disease was increased by 71%. This study — SELECT (Selenium and Vitamin E Cancer Prevention Trial) — was conducted by my colleagues at The Ohio State University, led by Theodore M. Brasky, PhD, from The Ohio State University Comprehensive Cancer Center in Columbus. This was published July 11, 2013 in the Journal of the National Cancer Institute.

This study was a randomized, placebo-controlled trial that was designed to evaluate whether selenium and vitamin E, alone or in combination, could reduce the risk for prostate cancer. The study looked at 35,533 black men aged 50 years or older or men of any race aged 55 years or older who had no history of prostate cancer and a serum prostate-specific antigen (PSA) level of 4 ng/mL. This particular analysis was a case-control substudy of SELECT. For each 50% increase in total long-chain omega-3 PUFA, there was an associated 22% to 25% increased cancer risk. The risk was associated with docosahexaenoic acid (DHA) concentration but not eicosapentaenoic acid (EPA).

These findings are definitely not new. These same researchers showed in 2011 that there was an association between high-risk prostate cancer and high concentrations of omega-3 fatty acids (Brasky TM. Am J Epidemiol. 2011;173:1429-1439). Nonetheless, they do conflict with an older study that found that, in men with a genetic predisposition to prostate cancer, a diet rich in omega-3 fatty acids was associated with a lower risk for prostate cancer (Berquin IM. J Clin Invest. 2007;117:1866-1875). In addition, a recent meta-analysis showed an association between omega-3 PUFA and a lower rate of breast cancer in women (Zheng JS. BMJ. 2013;doi:10.1136/bmj.f3706).

What we don’t know is if these levels were elevated from supplementation, a prescription form of fish oil or diet. We also don’t know if there are individual differences in metabolizing fish oil. Moreover, this was a population of men who were, as defined by the trial, at high risk for prostate cancer. This was essentially an observational study and, at this point, I don’t believe we should change how we manage patients, particularly those whom we treat with high-dose prescription omega-3s for very high triglycerides.

Of note, this study doesn’t prove that fish oil causes cancer. Rather, it shows that there is an association. Further, it is estimated that it would take three to four servings of fish per week to get into the highest exposure category. The current recommendation from the American Heart Association for heart disease prevention is one to two servings of oily fish per week, and there is nothing about this study that would make this recommendation inappropriate.

But what about those who are given fish oil to treat very high triglycerides and are taking up to 4 grams of EPA and/or DHA a day? For now, I recommend we continue treatment with omega-3s when appropriate until we have randomized trials that help guide us further. However, perhaps we can think about alternative drug therapies in those at risk for prostate cancer given this association. Indeed, consideration of omega-3s that contain no DHA, like icosapent ethyl (Vascepa, Amarin), might be a better choice in some men at risk for prostate cancer since it contains no DHA.

Nevertheless, this study has not proven that any supplementation of any sort caused prostate cancer. Certainly, there is much more for us to know about omega-3s in terms of supplementation vs. prescription vs. dietary sources. And here is hoping that this study is the bait we need to figure this out.

For more information:

Brasky TM. J Natl Cancer Inst. 2013;doi:10.1093/jnci/djt174.