Tumor Growth Inhibited by the Omega-3 PUFA DHA (docosahexaenoic acid)

As I have indicated in my blog on several occasions, consumption of the omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is one of the many important aspects of a healthy diet and lifestyle. You can, of course, read more information about these fats on the Omega-3 & Omega-6 Fatty Acid Synthesis, Metabolism, Functions page of my website.

Now a recent publication in the prestigious journal, Proceedings of the National Academy of Sciences demonstrates yet another blockbuster benefit to the consumption of these omega fats.

Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis

Numerous studies in both humans and laboratory animals have shown that omega-3 PUFAs can reduce the risk for certain types of cancers, however, the precise mechanism(s) by which these fats exert these effects is not completely understood. What is known, with respect to cancer, is that omega-3 PUFAs can inhibit the formation of new blood vessels, the process termed angiogenesis. Tumors require large amounts of nutrients and oxygen to grow and they accomplish this by stimulating the process of angiogenesis.

This most recent study has demonstrated that metabolic by-products of DHA (epoxydocosapentaenoic acids, EDPs), that are generated by normal hepatic cytochrome P450 (CYP) enzyme activity, inhibit VEGF- (vascular endothelial growth factor) and FGF-2- (fibroblast growth factor 2) induced angiogenesis. An additional striking and clinically significant finding from these studies was that the corresponding cytochrome P450 derived metabolites from the omega-6 PUFA, arachidonic acid (these metabolites are epoxyeicosatrienonic acids) actually stimulate angiogenesis and tumor progression.

These results also demonstrated that the epoxy metabolites of DHA are potent vasodilators and potent anti-inflammatory agents. The significance of the vasodilatory effects of DHA-derived epoxy metabolites stems from the fact that previous research has shown that targeting VEGF with inhibitors to restrict tumor-derived angiogenesis results in the induction of hypertension. Therefore, the DHA-derived epoxy metabolites may have unique advantages in antiangiogenic cancer therapy by avoiding the hypertension associated with VEGF inhibition.

The ideal diet of omega fatty acids is suggested to be in a 2:1 ratio of omega-6 to omega-3 PUFAs. However, in the typical Western-style diet that ratio is closer to 20:1. Now it is important to note that arachidonic acid is a good omega-6 PUFA as it is important in promoting the normal processes of inflammation (for example), however, in excess the consequences are excess inflammatory processes which contribute to obesity, diabetes, heart disease, and cancer. This latest research finding indicates one important mechanism by which too much omega-6 PUFA can, and likely, contributes to higher rates of certain types of cancer.

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