Life Extension Update
Omega-3 fatty acids reduce prostate cancer growth
The August 1, 2006 issue of the journal Clinical Cancer Research published the finding of researchers at UCLA that a greater ratio of omega-3 to omega-6 fatty acids in the diet was associated with a reduction in prostate tumor growth rates and prostate-specific antigen (PSA) levels in a mouse model of hormone-sensitive prostate cancer. Omega-3 fatty acids consist of EPA and DHA, found in oily fish and the algae that they feed on, and ALA, found in flax and other plants. Omega-6 fatty acids are found mainly in vegetable oils such as those derived from corn and safflower, and are also found in red meat.
David Geffen School of Medicine department of urology professor William Aronson and colleagues used immunodeficient mice injected with human prostate cancer cells for the current study. One group of mice was provided with a diet that contained 20 percent fat consisting of a 1 to 1 ratio of omega-3 to omega-6 fatty acids, while a second group received the same diet with its 20 percent fat content consisting mostly of omega-6 fatty acids. The animals’ weights and tumor volumes were measured weekly. After eight weeks the animals’ tumors were examined and blood serum was analyzed for PSA.
The research team found a 22 percent average reduction in tumor cell growth rates and 77 percent lower PSA levels among mice who received the omega-3 fatty acids compared to animals whose dietary fats were predominantly omega-6. Pro-inflammatory prostaglandin (PGE-2) levels were 83 percent lower in the tumors of mice who received the high omega-3 diet than in mice on the omega-6 fatty acid diet.
An increased omega-3 to omega-6 fatty acid ratio results in higher tumor EPA and DHA content and a reduction in arachidonic acid. These fatty acids compete to be converted by cyclooxgenase enzymes (COX) into prostaglandins, which can become either pro-inflammatory or anti-inflammatory and reduce growth. Higher levels of DHA and EPA may lead to development of more anti-inflammatory prostaglandins.
The study is among the first to demonstrate the effect of reducing a prostate cancer- promoting inflammatory response via diet. Dr Aronson commented, “Corn oil is the backbone of the American diet. We consume up to 20 times more omega-6 fatty acids in our diet compared to omega-3 acids. This study strongly suggests that eating a healthier ratio of these two types of fatty acids may make a difference in reducing prostate cancer growth, but studies need to be conducted in humans before any clinical recommendations can be made."
"We may be able to use EPA and DHA supplements while also reducing omega-6 fatty acids in the diet as a cancer prevention tool or possibly to reduce progression in men with prostate cancer," Dr Aronson added. The team is currently conducting a trial which will compare the effects of a low-fat diet supplemented with omega-3 fatty acids to those of a balanced Western diet on men whose prostate glands were removed due to prostate cancer.
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. Eicosanoids, and the balance of good versus bad eicosanoids, can be seen as the heart and soul, muscle, bone, and sinew, literally and figuratively, of holistic medicine.
Clearly pertinent to a discussion of prostate cancer (PC) is the fact that the first eicosanoids isolated in 1936 by Ulf von Euler were prostaglandins--eicosanoids isolated from the prostate gland. Eicosanoids are the oldest hormones, tracing their origin back 500 million years ago to production by sponges. Hormones are messengers involved in communication between cells. A hormone is formally defined as a substance, usually a peptide or steroid, produced by one tissue and conveyed by the bloodstream to another to affect physiological activity, such as growth or metabolism.
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 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 overexpressed 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.
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 PC 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.
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