Fish Oil May Favorably Alter Biology of Prostate Cancer

Roxanne Nelson

November 20, 2013

A low-fat diet and supplementation with fish oil appears to reduce proinflammatory substances in the blood of prostate cancer patients, according to a new study. It also decreased the cell cycle progression (CCP) score, which is a measure used to predict cancer recurrence.

The study was published online October 29 in Cancer Prevention Research.

It is a follow-up to an earlier clinical trial conducted by the same team, which found that men who ate a low-fat diet with fish oil supplements, consumed for 4 to 6 weeks prior to prostate removal, slowed the growth of cancer cells, compared with men in the control group who ate a traditional high-fat Western diet (Cancer Prev Res (Phila). 2011;4:2062-2071).

"We found that CCP scores were significantly lower in men who consumed the low-fat fish oil diet," said lead author William Aronson, MD, clinical professor of urology at the University of California, Los Angeles, and chief of urologic oncology at the West Los Angeles Veterans Affairs Medical Center. "We also found that men on the low-fat fish oil diet had reduced blood levels of proinflammatory substances that have been associated with cancer."

A number studies have investigated the relation between prostate cancer and omega-3 fatty acids. "To my knowledge, all preclinical studies suggest a potential benefit of fish oil and omega-3 fatty acids for the prevention and treatment of prostate cancer," Dr. Aronson told Medscape Medical News.

In preclinical studies, reducing dietary fat from corn oil (omega-6 fatty acids) and increasing fish oil intake (omega-3 fatty acids) has been shown to delay the development and progression of prostate cancer, the authors note.

But epidemiologic studies are mixed with regard to the benefit of fish oil for prevention and treatment, Dr. Aronson explained.

Mixed Results

A 2007 study found that for men with a genetic predisposition to prostate cancer, the consumption of a diet rich in omega-3 fatty acids might lower the risk for disease. A more recent study found that men who had high blood concentrations of long-chain omega-3 polyunsaturated fatty acids had a significant 43% increase in the risk for all grades of prostate cancer, compared with men who had the lowest concentrations, although that study was criticized as being flawed.

The study suggesting an increased risk with fish oil "received an enormous amount of press, but that is just one piece of the puzzle," Dr. Aronson noted. "Other studies show the opposite or a beneficial effect."

"There are contradictions and, clearly, further prospective randomized trials are indicated, given the numerous articles suggesting potential benefits of fish oil," he continued. "In our study, we combined fish oil with a low-fat diet. This allows for a reduction in intake of omega-6 fatty acids, which stimulate cancer development and growth in preclinical studies, and an increase in omega-3 fatty acids."

He added that they believe this is a novel and rational approach. "Just taking a nutritional supplement or vitamin pill alone, without also changing the diet, may not effectively prevent or treat prostate cancer."

The previous phase 2 randomized trial by Dr. Aronson's team involved 55 patients undergoing radical prostatectomy. One group ate a low-fat diet with 5 g of fish oil daily (2:1 ratio of dietary omega-6/omega-3) or a control Western diet (15:1 ratio of omega-6/omega-3) for 4 to 6 weeks prior to surgery. The primary end point was change in serum insulin-like growth factor 1 (IGF-1) between the study groups. Secondary end points were changes in serum IGFBP-1, prostate prostaglandin E2 levels, omega-6/omega-3 fatty acid ratios, COX-2, and markers of proliferation and apoptosis.

The primary outcome (serum IFG-1 levels) was negative, but positive secondary outcomes with the low-fat fish oil diet included reduced benign and malignant prostate tissue omega-6/omega-3 ratios, reduced proliferation (Ki-67 index), and reduced proliferation in an ex vivo bioassay when patient serum was applied to prostate cancer cells in vitro.

Intervention Lowered Markers

In the current study, Dr. Aronson's team evaluated the effect of the low-fat fish oil diet on 2 serum proinflammatory eicosanoids — 15(S)-HETE and leukotriene B4 (LTB4) — and the CCP score. They measured serum fatty acids and eicosanoids with gas chromatography and ELISA, and measured the CCP score with reverse transcriptase-polymerase chain reaction.

In addition, the associations between serum eicosanoids, Ki67, and CCP score were evaluated using partial correlation analyses, and BLT1 (LTB4 receptor) expression was determined in prostate cancer cell lines and prostatectomy specimens.

This post hoc analysis used serum and prostate tissue obtained in the original study.

The majority of men in the 2 groups were either overweight or obese, and the average diet duration was 28 to 30 days. Patients in both groups were compliant with the diet, and those in the low-fat group were compliant with fish oil capsule consumption.

CCP score was significantly lower with the low-fat fish oil diet than with the control diet (P = .03).

In men who ate the low-fat fish oil diet, there was a significant decrease in the mean level of total omega-6 fatty acids, an increase in the level of total omega-3 fatty acids, and a decrease in the omega-6/omega-3 fatty acid ratio.

There was also a significant decrease in circulating levels of the proinflammatory eicosanoid 15(S)-HETE with the low-fat fish oil diet. In addition, postintervention 15(S)-HETE circulating levels were significantly lower than preintervention levels.

Even though there was no difference in LTB4 levels between the low-fat fish oil group and the control group, postintervention LTB4 levels in the low-fat fish oil group were significantly lower than preintervention levels.

The LTB4 receptor BLT1 was detected in prostate cancer cell lines and human prostate cancer specimens. In a statement, Dr. Aronson said that the team plans to conduct further studies to determine the importance of this novel receptor in prostate cancer progression.

No Clinical Recommendations Yet

"We are extremely encouraged by our findings, but at this time, would not make clinical recommendations with regard to a low-fat diet or fish oil capsules for the prevention or treatment of prostate cancer," Dr. Aronson said. "Based on our positive findings, the National Institutes of Health has provided funding for a 1-year trial, which we will begin in early 2014."

The study was supported with resources and the use of facilities at the West Los Angeles Veterans Administration Medical Center, Myriad Genetics Laboratories, and NIH grants. The authors have disclosed no relevant financial relationships..

Cancer Prev Res. Published online October 29, 2013. Abstract

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