Effects of Omega-3 versus Omega-6 on Metabolism and their Role in the Development of Diseases - Research Paper Example

? June Effects of Omega-3 versus Omega-6 on Metabolism And their Role in Development of Diseases Introduction In mammals, dietary fat is an important source of energy. Studies have shown that certain fatty acids, namely – alpha-linolenic acid (ALA; omega-3 fatty acid) and linoleic acid (LA; omega-6 fatty acid) are extremely vital for the normal physiological functioning, growth and development of mammals. They are termed as essential fatty acids as they cannot be synthesized in the body and can only be obtained through diet. Both these polyunsaturated fatty acids (PUFAs) utilize the same enzymes during metabolism, and hence, compete for enzyme availability (Simopoulos, 2010). Therefore, the ratio in which both these fatty acids are present in the body dramatically influences its physiology. This paper discusses the effects of omega-6 vs. omega-3 on metabolism and development of diseases in the human body. Metabolism and Physiological Importance of PUFAs As already stated, there are two classes of PUFAs in the human body – omega-3 and omega-6. These two essential fatty acids are derived from the diet. They serve as precursors for various other fatty acids required by the body. LA or omega-6 fatty acid serves as the precursor for the n-6 series while ALA or omega-3 fatty acid serves as the precursor for the n-3 series of fatty acids (Patterson et al., 2012). These regulate various physiological functions ranging from modulation of blood pressure and clotting to the proper functioning and development of the nervous system. Furthermore, omega-6 PUFAs such as arachidonic acid (AA) and omega-3 PUFAs such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are precursors of eicosanoids, which regulate inflammation and immunity. The metabolism of ALA and LA into various other long chain fatty acids occurs through a series elongation and desaturation steps with the help of elongase and desaturase enzymes (Simopoulos, 2010). Ecosanoids derived from omega-6 are proinflammatory while those derived from omega-3 are anti-inflammatory. Figure 1: Diagrammatic representation of the desaturation and elongation of omega-3 and omega-6 fatty acids into long chain fatty acids. Role of the Ratio between Omega-3 and Omega-6 Fatty Acids in the Development of Diseases As stated by Simopoulos, “human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of ~1 whereas in Western diets the ratio is 15/1–16.7/1” (2008, p. 674). Excessive consumption of omega-6 fatty acids at the expense of omega-3 fatty acids leads to a high omega-6/omega-3 ratio. High omega-6/omega-3 ratio is associated with the pathogenesis of several diseases including cancer, cardiovascular diseases, autoimmune diseases, chronic inflammatory diseases such as NAFLD (nonalcoholic fatty liver disease), rheumatoid arthritis, obesity, in?ammatory bowel disease (IBD), and Alzheimer’s disease (Patterson et al., 2012; Simopoulos, 2008). Diets having lower omega-6/omega-3 ratio that are higher in omega-3 fatty acids are found to have suppressive effects on these diseases. The Lyon Diet Heart Study has shown that reducing the ratio to 4/1 led to a 70% reduction in the risk of recurrent cardiovascular diseases, leading to decreased mortality in two years (Kris-Etherton et al., 2001). In another study, de Lorgeril et al. (1995) have shown that Mediterranean diet rich in alpha-linolenic acid (omega-3 fatty acid) is “more efficient than presently used diets” for the prevention of cardiovascular disease and associated mortality (p. 1454). Omega-6/omega-3 ratio is found to be significantly associated with NAFLD. Araya et al. (2004) found that the level of omega-3 fatty acids is reduced in hepatic tissue of patients suffering from NAFLD. They have further shown that a higher omega-6/omega-3 ratio occurs in the liver of these patients, due to which, there may be a higher synthesis of lipids rather than oxidation and secretion, resulting in steatosis. Studies have also shown that in patients with colorectal cancer, rectal cell proliferation is fairly reduced when the omega-6/omega-3 ratio is brought down to 2.5/1 (Simopoulos, 2008). In a study by Murff et al., which aimed to investigate the relation between PUFAs and colorectal cancer risk, it was shown that the omega-6/omega-3 ratio is positively associated with the risk or colorectal cancer (2009). They state that PGE2 production may be linked to such an association. In another study, Murff et al. (2012) found that higher intake of omega-3 fatty acid derived from marine foods lead to a lower risk of colorectal polyps in women. Contrarily in men, however, increased dietary intake of ALA was associated with an increased risk of hyperplastic colorectal polyps in men. Clinical trials demonstrate that a lower omega-6/omega-3 ratio leads to a reduction in the risk of breast cancer in women. DHA and EPA cause induction of apoptosis in cancer cells and reduce the expression of procaspase-8 and Bcl2, apart from reducing cell viability (Corsetto et al., 2011). The activation of EGFR is also reduced. Consumption of omega-3 fatty acids may thus lead to a modification in the cell membrane structure in breast cancer, leading to an increase in the degree of unsaturation of fatty acids (Corsetto et al., 2011). Omega-6/omega-3 ratio is also significantly associated with the incidence of inflammatory bowel disease. Consumption of diets rich in omega-3 fatty acids derived from fish oil has been shown to reduce the prevalence of inflammatory bowel disease (Patterson et al., 2012). This association was investigated in Greenland Eskimos by Bang, Dyerberg, and Sinclair. Studies also report that supplementation of omega-3 fatty acids in patients with inflammatory bowel disease leads to a reduction in inflammation, mediated by a decrease in the production of LTB4 by colon mucosa and neutrophils upon incorporation of the omega-3 fatty acid in the mucosal tissue of the gut (Patterson et al. 2012). Studies have also shown that the ratio of omega-6 to omega-3 fatty acid is directly associated with brain development and neurological function. The ratio of AA and DHA in the diet significantly influence neurodegeneration associated with neurodegenerative diseases (Farooqui, Horrocks, and Farooqui, 2007). Conclusion PUFAs are extremely vital molecules involved in various physiological functions. They modulate the production of eicosanoids, cytokines and plasma lipids. Clinical trials and research studies have confirmed the cancer suppressing and cancer preventing properties of omega-3 fatty acids. The ratio of omega-6/omega-3 fatty acids in the diet greatly affects the physiological functioning of the body. This paper discussed the role of omega-6/omega-3 ratio in the development of diseases. The metabolism of PUFAs has also been briefly discussed. Works Cited Araya, J, et al. “Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease.” Clinical Science 106.6(2004):635-643. Corsetto, Paola, et al. “Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane.” Lipids in Health and Disease 10.73(2011). de Lorgeril, M, et al. “Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.” Lancet 343.8911 (1995):1454-1459. Farooqui, AA, LA Horrocks, T Farooqui. “Modulation of inflammation in brain: a matter of fat.” Journal of Neurochemistry 101.3(2007):577-99. Kris-Etherton, Penny, et al. “Lyon Diet Heart Study: Benefits of a Mediterranean-Style, National Cholesterol Education Program/American Heart Association Step I Dietary Pattern on Cardiovascular Disease.” Circulation 103 (2001): 1823-1825. Murff, Harvey, et al. “A Prospective Study of Dietary Polyunsaturated Fatty Acids and Colorectal Cancer Risk in Chinese Women.” Cancer Epidemiology, Biomarkers & Prevention 18(2009): 2283. Murff, Harvey, et al. “Dietary intake of PUFAs and colorectal polyp risk.” The American Journal of Clinical Nutrition (2012):doi: 10.3945/?ajcn.111.024000. Patterson, E, R Wall, GF Fitzgerald, RP Ross, and C. Stanton. “Health Implications of High Dietary Omega-6 Polyunsaturated Fatty Acids.” Journal of Nutrition and Metabolism (2012): doi:10.1155/2012/539426. Simopoulos, Artemis. “Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk.” Experimental Biology and Medicine 235.7 (2010): 785-795. Simopoulos, Artemis. “The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases.” Experimental Biology and Medicine 233.6 (2010): 674-688. Read More