Omega-6 and Omega-3 Fatty Acids and Prostaglandin Metabolism
Omega-6 fatty acids account for the majority of polyunsaturated fatty acids (PUFA) in the food supply. They are the predominant PUFA in all diets, especially Western diets. When diets are supplemented with omega-3 fatty acids, the latter partially replace the omega-6 fatty acids in the membranes of practically all cells (i.e., erythrocytes, platelets, endothelial cells, monocytes, lymphocytes, granulocytes, neuronal cells, fibroblasts, retinal cells, hepatic cells and neuroblastoma cells).
Competition between the omega-6 and omega-3 fatty acids occurs in prostaglandin formation. Eicosapentaenoic acid (EPA), an omega-3 fatty acid, competes with arachidonic acid (AA), an omega-6 fatty acid, for prostaglandin and leukotriene synthesis at the cyclooxygenase and lipoxygenase level(Fig. 1). When humans ingest fish or fish oil, the EPA and docosahexaenoic acid (DHA) from fish or fish oil lead to (1) a decreased production of prostaglandin E2 (PGE2) metabolites, (2) a decrease in thromboxane A2, a potent platelet aggregator and vasoconstrictor (3) a decrease in leukotriene B4 formation, an inducer of inflammation and a powerful inducer of leukocyte chemotaxis and adherence, (4) an increase in thromboxane A3, a weak platelet aggregator and a weak vasoconstrictor, (5) an increase in prostacyclin PGI3, leading to an overall increase in total prostacyclin by increasing PGI3 without a decrease in PGI2 (both PGI2 and PGI3 are active vasodilators and inhibitors of platelet aggregation) and (6) an increase in leukotriene B5, a weak inducer of inflammation and a weak chemotactic agent [10,11]. Omega-3 fatty acids modulate prostaglandin metabolism and decrease triglycerides and, in high doses, lower cholesterol and have antithrombotic and anti-inflammatory properties. These studies were extensively reviewed and reported [12–17].
Many factors contribute to the complex course of inflammatory reactions. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of interleukins and lipid mediators are released and play a crucial role. Pro-inflammatory eicosanoids of AA metabolism are released from membrane phospholipids in the course of inflammatory activation. EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.
A variety of substances that inhibit the COX pathway have been investigated, including non-steroidal anti-inflammatory drugs (NSAIDs) used for the treatment of inflammation, pain and fever. Although NSAIDs inhibit COX and are efficacious anti-inflammatory agents, serious adverse effects limit their use. Two forms of COX have been identified, a constitutively expressed COX-1 and a cytokine inducible COX-2. It has been suggested that NSAID toxicity is due to inhibition of COX-1, whereas therapeutic properties are derived from COX-2 inhibition at the site of inflammation [18,19]. In addition, there is evidence that COX-2 inhibition can suppress the growth of colorectal cancer [20].
A new arena for omega-3 fatty acids has emerged as adjuvants to drug treatment leading to synergism (potentiating the effects of drugs) or to decreasing their toxicity (Table 1) [21–32].
Categories: Omega-3 Anti-Inflammatory, Omega-6 Pro-Inflammatory, Science
Tags: COX-2, cytokines, interlukin 6, Omega-3, omega-6, pro-inflammatory, prostaglandin, PUFAs
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