March 24, 2009

Greater omega-3 fatty acid intake associated with decreased risk of advanced prostate cancer

In an article published online on March 24, 2009 in the American Association for Cancer Research journal Clinical Cancer Research, scientists from the University of California, San Francisco report a protective effect of long chain omega-3 polyunsaturated fatty acids against advanced prostate cancer risk.

Professor of epidemiology and biostatistics John S. Witte, PhD and his associates compared 466 men with aggressive prostate cancer to 478 healthy men matched for age and ethnicity. Dietary questionnaire responses were evaluated for omega-3 fatty acid intake, and blood samples were analyzed for nine variants in the gene that controls cylooxygenase-2 (COX-2), an enzyme involved in fatty acid metabolism, inflammation and cell proliferation. Earlier research has demonstrated decreased expression of COX-2 among animals fed high omega-3 fatty acid-containing diets, as compared to high omega-6 diets.

Advanced prostate cancer risk declined with increasing omega-3 fatty acid intake. Men whose intake of omega-3 fatty acids was among the top 25 percent of participants had a 63 percent lower risk of aggressive prostate cancer compared with those whose intake was in the lowest fourth. This association was stronger among men with a particular modification of the gene that controls COX-2 expression, resulting in an over five times greater risk of advanced prostate cancer in men with this variant who reported a low intake of omega-3 fatty acids. "Previous research has shown protection against prostate cancer, but this is one of the first studies to show protection against advanced prostate cancer and interaction with COX-2," Dr Witte stated. "The COX-2 increased risk of disease was essentially reversed by increasing omega-3 fatty acid intake by a half a gram per day."

"If you want to think of the overall inverse association in terms of fish, where omega-3 fatty acids are commonly derived, the strongest effect was seen from eating dark fish such as salmon one or more times per week," he added.

"Our study provides additional support for the role of inflammation in prostate cancer susceptibility and progression," the authors conclude. "More clinical and biological studies are needed to decipher how dietary long chain omega-3 and other factors involved with inflammation such as COX-2 genotypes affect aggressive prostate cancer."

Prostate cancer/prostate health

Eicosanoids are hormones that are made within the cell membrane of each and every cell--all 60 trillion cells in the human body. Eicosanoids are 20-carbon structures. Eicosanoids have autocrine, paracrine, and endocrine effects. That is, they affect the very cell that produces the eicosanoid (autocrine effect), as well as nearby cells (paracrine effect) and distant cells (endocrine effect). As with every aspect of biology, balance is a critical issue relating to good health as well as the development and progression of various diseases. Likewise, eicosanoid balance plays a central role that puts this desired biological endpoint at the hub of the integrative medicine wheel.

Eicosanoid synthesis involves the release of arachidonic acid (AA) from cell membrane phospholipids by an enzyme called phospholipase A2 (PLA2). AA then undergoes metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs). AA is an omega-6 fatty acid that is known to generate free radicals and is considered an unfavorable eicosanoid. Specific metabolites of AA, for example, PGE2 and 5-HETE, are created through the actions of the enzymes COX-2, 5-LOX, 12-LOX, and 15-LOX. These metabolites are examples of bad eicosanoids and have been implicated in prostate cancer (PC) growth and metastasis. In a study of human PC in which 5-LOX and its metabolite 5-HETE were evaluated in both malignant and benign prostate tissue within the same patient, both 5-LOX and 5-HETE were significantly over-expressed in the PC tissue. In other words, specific eicosanoids are modulators of tumor cell interactions with certain host components within the context of cancer growth, invasion, and spread.

The administration of PGE2 to prostate, breast, and colon cancer cells resulted in increased cellular proliferation. Some studies have shown that stimulation of PC growth is related more to COX-2 and a resultant increase in angiogenesis than to PGE2.

EPA, an omega-3 fatty acid, has been shown to suppress AA formation by inhibiting the enzyme delta-5-desaturase. Some epidemiologic studies have shown that high intakes of EPA and DHA lower prostate cancer risk substantially. Other studies have shown a reduction in PC risk only with a decrease in the ratio of AA to EPA (AA:EPA). A combination of GLA and EPA administered to humans was shown to strongly increase serum EPA and DGLA levels and to reduce AA formation and AA metabolites such as leukotrienes.

Foods rich in EPA include coldwater fish such as tuna, sardines, herring, swordfish, and salmon. Commercially available pharmaceutical-grade fish oils also contain large amounts of EPA and DHA.

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Life Extension Update

• Flaxseed reduces prostate tumor proliferation
• Omega-3 fatty acids reduce prostate cancer growth

What's Hot

• Flaxseed arrests prostate tumor growth
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Life Extension magazine

• Advances in prostate cancer chemoprevention and treatment
• Eating your way to prostate cancer

If you have questions or comments concerning this issue or past issues of Life Extension Update, send them to ddye@lifeextension.com or call 954 202 7716.

For longer life,

Dayna Dye
Editor, Life Extension Update
ddye@lifeextension.com
954 766 8433 extension 7716
www.lef.org
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