On July 10, 2013, Theodore M. Brasky, PhD, of the Ohio State University Comprehensive Cancer Center in Columbus, and colleagues published a study in the Journal of the National Cancer Institute (2013;105:1132-1141) that they said confirms previous reports of increased prostate cancer (PCa) risk among men with high blood levels of long-chain omega-3 polyunsaturated fatty acids.

Two months later, a team led by James J. DiNicolantonio, PharmD, of the Mid America Heart Institute at Saint Luke’s Hospital in Kansas City, Mo., and Wegmans Pharmacy in Ithaca, N.Y., presented its own take on those results, noting in Missouri Medicine (2013;110:292-295) that “the Brasky paper only demonstrates an association between plasma phospholipid omega-3s and subsequent prostate cancer risk; it cannot prove that omega-3 fatty acids (and particularly fish oil) cause prostate cancer.”

Dr. DiNicolantonio and his coauthors, including two cardiovascular physicians, further contended that a more thorough review of the pertinent literature suggests that increased omega-3 fatty acid consumption does not increase PCa risk, and notably decreases PCa mortality, while “most certainly” reducing risk for sudden death and cardiovascular events

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“I think that when you actually read the Brasky paper, one would not be concerned with fish oil supplements increasing the risk of prostate cancer, but the press releases that came afterwards confused clinicians and the public alike, causing a lot of panic,” Dr. DiNicolantonio told Renal & Urology News.

“Also, it is highly likely that a lot of people stopped their fish oil supplements based on inappropriate conclusions drawn from this study, and it would be a shame for patients on fish oil supplements to lose the cardiovascular protection that has been shown for decades with these supplements.”

Dr. DiNicolantonio pointed out that Dr. Brasky and his co-authors analyzed data from a single blood measurement of omega-3 status, and that one omega-3 blood draw—particularly one that does not measure omega-3 levels in red blood cells, which is a more accurate reflection of chronic omega-3 intake—cannot implicate fish oil supplements as causing PCa.

“Patients should not stop their fish oil supplements based on the Brasky paper,” Dr. DiNicolantonio said.

The National Institute of Health’s (NIH’s) MedlinePlus service names mackerel, tuna, salmon, sturgeon, mullet, bluefish, anchovy, sardines, herring, trout, and menhaden as the fish especially rich in omega-3 fatty acids.

When asked what misconception about the relationship between omega-3 fats and PCa he would most like to clear up, Dr. DiNicolantonio noted that a plethora of prior studies looking at fish intake—particularly fatty fish and non-fried fish—as well as fish oil supplement intake show a decreased risk of PCa.

“People who have a lifelong high intake of fish have some of the lowest rates of prostate cancer or prostate cancer mortality, such as Eskimo men and Japanese men,” he said.

3s beat 6s

Dr. DiNicolantonio and associates have submitted for publication a paper in which they show that maintaining a low ratio of omega-6 fatty acids (found in corn, safflower, sunflower, and soybean oils, as well as in nuts and seeds) to omega-3 fatty acids is probably one of the best measures for reducing carcinoma, particularly carcinoma promoted by COX-2 activity, such as PCa.

Physicians who want to help men prevent the development of PCa should urge these patients to eat less of the leaner fish, such as tilapia, which has higher omega-6 content and lower omega-3 content, and to eat more fatty fish such as salmon, he advised. The fish should be baked, not fried.

“Fish from the ocean will have the desired higher omega-3 content and lower omega-6 content than will farm-raised fish, because fish get their high levels of omega-3 from eating oceanic algae,” Dr. DiNicolantonio explained.

Achieving a favorable ratio of omega-6 fats to omega-3 fats is also being studied by William J. Aronson, MD, chief of urologic oncology at the West Los Angeles Veterans Affairs Medical Center and a clinical professor of urology at University of California Los Angeles. Yet Dr. Aronson’s work is focused not on preventing PCa but on delaying its progression.

He and his colleagues recently demonstrated that men with PCa who ate a low-fat diet and took fish oil supplements for four to six weeks prior to radical prostatectomy later had lower levels of pro-inflammatory substances in their blood and a lower Cell Cycle Progression score in their prostate tissue (as compared with a control Western diet group), suggestive of potential beneficial effects of the low-fat diet plus fish oil capsules, according to a report in Cancer Prevention Research (2014;7:97-104).

“The subtlety between preventing prostate cancer development and prostate cancer progression is that as men get older, most of them probably have small foci of these slower-growing prostate cancers, and no one ever finds them clinically,” Dr. Aronson pointed out. “So if you’re preventing something, how are you doing it? Is the action on the cells that might become cancer, or are you having the action on the foci of cells in there that are cancer and just preventing them from becoming clinical cancer?”

Dr. Aronson acknowledged that the answer to this complex question remains unknown. “Our next trial, which is launching in April, will randomize men with prostate cancer who have elected active surveillance to either a control group or a group that gets fish oil capsules combined with a low-fat diet.”

According to Dr. Aronson, the typical ratio of omega-6 fats to omega-3 fats in the American diet is approximately 15 to 1. The typical ratio in the Asian diet is 4 to 1, and PCa is less prevalent among men living in Asia. “In our recently reported clinical trial, we manipulated the diet and fish oil capsules so the omega-6-to-omega-3 ratio was 2 to 1,” Dr. Aronson recounted. “So it was a favorable ratio, and we saw potentially favorable effects on the cancer.”

For now, Dr. Aronson does not counsel his PCa patients to consume fish oil. “At this point I’m advising a heart-healthy diet and weight loss if needed, because cardiovascular disease is still the number 1 cause of death in prostate cancer patients. I don’t even mention fish oil. But if the patient brings it up, I simply say, ‘We’re really interested in that, and we’re doing more research in that important area. But I don’t recommend it.’”