High Levels of Fish Oil May Boost Risk for Prostate Cancer

Roxanne Nelson

July 19, 2013

UPDATED August 1, 2013 — A high intake of omega-3 fatty acid, which is found in fish oil, might significantly boost the risk of developing prostate cancer, according to a prospective study.

Overall, men who had high blood concentrations of long-chain omega-3 polyunsaturated fatty acids (PUFA) had a significant 43% increase in the risk for all grades of prostate cancer, compared with men who had the lowest concentrations. The risk for high-grade disease was increased by 71%.

The results of the study, led by Theodore M. Brasky, PhD, from the Ohio State University Comprehensive Cancer Center in Columbus, were published online July 11 in the Journal of the National Cancer Institute.

However, the study design has serious flaws, and the conclusions about prostate cancer are not valid, according to urology expert Gerald Chodak, MD, director of the Midwest Prostate and Urology Health Center in Michiana Shores, Indiana. In a recent expert video commentary on Medscape's Chodak on Urology, he discusses the design of the study in some detail, and raises questions about the control group and the way in which prostate cancer was diagnosed.

Previous Findings

According to Dr. Brasky and colleagues, their study confirms previous reports of increased prostate cancer risk in men with high blood concentrations of omega-3 fatty acids.

A previous study by the same team in a different cohort of men found a similar link between high serum concentrations of omega-3 fatty acids and a large increase in the risk for high-grade prostate cancer (Am J Epidemiol. 2011;173:1429-1439).

The men in the current study were participants in SELECT (Selenium and Vitamin E Cancer Prevention Trial), which is a large randomized trial.

We recommended moderating fish intake and avoiding supplements.

"The 2 sources of these fatty acids in blood are food and supplements, so the blood samples represent total exposure," Dr. Brasky told Medscape Medical News. "The results shouldn't change with the source of the fats," he said.

However, "given that supplements represent mega doses of omega-3s, we recommended moderating fish intake and avoiding supplements," he added.

Conflicting Data

Previous studies have reported conflicting results on the benefits and risks of fish oils, either consumed as fish or in supplements, in cancer patients.

Fish oil supplements were associated with a lower risk for breast cancer in postmenopausal women in the Vitamins and Lifestyle (VITAL) cohort study (Cancer Epidemiol Biomarkers Prev. 2010;19:1696-1708), as previously reported by Medscape Medical News. Although that study, which was also led by Dr. Brasky, found that "fish oil is a potential candidate for chemoprevention studies," it is currently "not recommended for individual use for breast cancer prevention."

Another study found that in men with a genetic predisposition to prostate cancer, the consumption of a diet rich in omega-3 fatty acids can lower the risk for disease (J Clin Invest. 2007;117:1866-1875). In that study, a diet high in omega-3 fatty acid reduced prostate tumor growth and increased survival, but omega-6 fatty acids had the opposite effects.

Omega-3 vs Omega-6

Chronic inflammation has been associated with cancer risk, and omega-3 fatty acids, which are found primarily in fatty fish and fish oil supplements, have anti-inflammatory effects. In contrast, other fats, such as the omega-6 fats in vegetable oil and the trans-fats commonly found in fast food, can promote inflammation.

Eicosapentaenoic acid (EPA), docosapentaenoic acid, and docosahexaenoic acid (DHA) are anti-inflammatory and metabolically related fatty acids derived from fatty fish and fish oil supplements. However, in the current study, they were associated with statistically significant increases in prostate cancer risk.

In contrast, linoleic and arachidonic acids, which are the primary omega-6 fatty acids associated with increased inflammation, were inconsistent, Dr. Brasky and his team note.

In fact, in the current study, concentrations of linoleic acid above the lowest quartile were associated with a lower cancer risk, without any evidence of a linear trend, whereas concentrations of arachidonic acid were not associated with cancer risk. Findings for trans-fatty acids, which are also associated with increased inflammation, were also inconsistent.

More Definitive Research Needed

Eliot Brinton, MD, director of atherometabolic research at the Utah Foundation for Biomedical Research in Salt Lake City, who was asked by Medscape Medical News to comment on the findings, said the data suggest that there might be an effect.

However, "this is an observational study, and these studies usually generate rather than confirm hypotheses," he explained. "For observational data, they came to a fairly strong conclusion. It is a little puzzling, interesting, and provocative. It raises questions but is a long way from being definitive."

"It highlights the potential differences between DHA and EPA," Dr. Brinton added. "More definitive studies are needed that address that."

Dr. Brinton pointed out that recent observational data have shown a benefit in breast cancer, so the effect doesn't appear to be uniform across cancer types. There is also limited information about how the blood levels were reached. "We don't know if it was from supplementation, a prescription for fish oil, or diet," he said, "or possibly the manner in which the omega-3 fatty acids were metabolized."

He noted that many population studies have shown the benefits of fish intake. "There remains a consensus among nutrition scientists that eating fish remains healthy, with caveats," he said. "However, the results of this study might 'temper the enthusiasm' for dietary supplements."

"Many have been guilty of pushing fish oil supplements, and physicians often misunderstand them," he said. "They may be good for some people, but it doesn't mean we should be putting everyone on fish oil. It should give us some hesitation about rubber stamping low-dose fish oil."

"Of course, it's not always harmful, but we probably shouldn't be assuming that it is healthy for everyone," Dr. Brinton added. "But we don't know at this point who it is healthy for, and that is what we need to find out."

Study Details

In the current study, Dr. Brasky and colleagues examined the association between plasma phospholipid fatty acids and prostate cancer risk in men who participated in SELECT. The randomized placebo-controlled trial was designed to evaluate whether selenium and vitamin E, alone or in combination, could reduce the risk for prostate cancer. The study population of 35,533 involved black men 50 years or older or men of another race 55 years or older who had no history of prostate cancer and a serum prostate-specific antigen (PSA) level of 4 ng/mL.

The case–cohort study was nested within SELECT. Cases were men with baseline blood samples available for analysis who were diagnosed with incident primary prostate cancer before July 31, 2009. This analysis was one of the secondary aims of the original trial, explained Dr. Brasky.

In continuous models, the researchers found that with each 50% increase in total long-chain omega-3 PUFA, there was an associated 22% to 25% increased cancer risk. Results for the individual long-chain omega-3 PUFA were similar, but the effect sizes tended to be smaller, and not all reached statistical significance.

Of the major omega-6 PUFA, higher levels of linoleic acid were associated with a 25% reduced risk for low-grade cancer and a 23% reduced risk for total cancer, but there was no dose response.

The researchers explored the possibly that the higher risk for prostate cancer might be explained by increased screening among those who consume high amounts of omega-3 PUFA. In a separate sensitivity analysis, they censored noncase individuals at the date of their last screening test, but found the results largely unchanged. Hazard ratios for associations between total long-chain omega-3 PUFA and total, low-grade, and high-grade prostate cancer were 1.44, 1.44, and 1.67, respectively.

This work was supported in part by grants from the National Cancer Institute and the National Center for Complementary and Alternative Medicine. The authors have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online July 11, 2013. Abstract


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