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Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases -2

Artemis P. Simopoulos, MD, FACN  Return to main Omega-3 page

The Center for Genetics, Nutrition and Health, Washington, D.C
 Continued from previous  page

 Other Inflammatory Markers, Interleukin-6 (IL-6) and Cardiovascular Disease

Atherosclerosis and inflammation share similar basic mechanisms involving the adhesion of leukocytes to vascular endothelium in their early phases. There is a strong association between systemic inflammation and coronary artery disease. This association is thought to be causal, i.e. inflammation increases the risk of the disease, rather than simply marking the presence of atherosclerosis, which is an inflammatory process . The relationship between infection and cardiovascular disease is likely to have several mediators (including possibly an autoimmune response against protein on the arterial endothelial cell wall). Cigarette smoking is a well established cardiovascular disease risk factor , as is high body mass index (BMI) , both providing a link between increased inflammation and increased risk. Although regular exercise reduces the risk of cardiovascular events, severe exercise has been shown to be associated with a systemic inflammatory response  and increased risk of myocardial infarction . In contrast to the risks of severe exercise, moderate exercise and physical fitness are associated with lower baseline levels of inflammatory mediators .
Inflammatory markers such as C-reactive protein and fibrinogen are raised in affected people in both chronic coronary artery disease  and peripheral vascular disease compared with unaffected people . The degree of inflammation correlates with disease severity .
Interleukin-6 (IL-6) is produced and released into the systemic circulation from subcutaneous adipose tissue as well as from cells of the immune system . The levels correlate with BMI and percent body fat. A recent theory is that increased IL-6 may be the link between obesity and insulin resistance . Adipose tissue secretes IL-6 whose levels and those of C-reactive protein also correlate with obesity and insulin resistance. There is strong evidence supporting the central role of IL-6 in the inflammatory response. IL-6 is a 26 kDa cytokine, produced by many different cells in the body, including lymphocytes, monocytes, fibroblasts and endothelial cells.


Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases


Fig. 2. The central role of interleukin-6 and its effect on the development of coronary artery disease [



    Fatty Acids, Cytokines, and Major Depression
Psychologic stress in humans induces the production of proinflammatory cytokines such as interferon gamma (IFN), TNF, IL-6 and IL-10. An imbalance of omega-6 and omega-3 PUFA in the peripheral blood causes an overproduction of proinflammatory cytokines.  Lower serum HDL cholesterol and an increased C20:46/C20:53 ratio are related both to depression and to a higher risk of cardiovascular disease, which shows a strong comorbidity with depression [79,80]. There are a number of studies evaluating the therapeutic effect of EPA and DHA in major depression. Stoll and colleagues have shown that EPA and DHA prolong remission, that is, reduce the risk of relapse in patients with bipolar disorder [84,85].

    Rheumatoid Arthritis
Interest in the use of omega-3 fatty acids EPA and DHA in rheumatoid
There are at least 13 randomized controlled clinical trials that show benefit from fish oil supplements in patients with rheumatoid arthritis [92]. A common feature of the studies has been a reduction in symptoms and in the number of tender joints. There was a reduction in the dose of analgesic anti-inflammatory drugs. In a subsequent meta-analysis, morning stiffness was decreased, as well as the number of tender joints [93].  Therefore, persons at a higher risk because of genetic susceptibility are good subjects to carry out preventive measures through dietary change by decreasing the omega-6 fatty acid and increasing the omega-3 fatty acid intake.

    Inflammatory Bowel Disease
Crohn’s disease and ulcerative colitis, collectively known as inflammatory bowel disease,  fish oil supplementation, which increases production of B5 and decreases production of B4, did indeed reduce the contents of rectal dialysates of leukotrienes. The clinical improvement was modest.


Asthma is a mediator driven inflammatory process in the lungs and the most common chronic condition in childhood. The leukotrienes and prostaglandins are implicated in the inflammatory cascade that occurs in asthmatic airways. There is evidence of airway inflammation even in newly diagnosed asthma patients within two to twelve months after their first symptoms [99]. Among the cells involved in asthma are mast cells, macrophages, eosinophils and lymphocytes.
. In other studies fish oil was successfully used in combination with etretinate to reduce the hyperlipidemia caused by that drug. In patients treated with ultraviolet B (UVB), omega-3 fatty acids prolong the beneficial effects of a course of phototherapy [24]. Fish oil in combination with cyclosporin reduces nephrotoxicity, which is the major side effect of that drug [24].


The anti-inflammatory properties of{omega}3 fatty acids, especially EPA, are due to competition with arachidonic acid (AA)

The importance of omega-3 essential fatty acids in the dietis now evident, as well as the need to return to a more physiologic omega-6/omega-3 ratio of about 1-4/1 rather than the ratio of 20-16/1 provided by current Western diets. In order to improve the ratio of omega-6/omega-3 essential fatty acids, it will be necessary to decrease the intake of omega-6 fatty acids from vegetable oils and to increase the intake of omega-3 fatty acids by using oils rich in omega-3 fatty acids and increase the intake of fish to two to three times per week or take supplements.Omega-3 fatty acids have been part of our diet since the beginning of time. It is only for the past 150 years that omega-3 fatty acids have been decreased in Western diets due to agribusiness and food processing. The need to return the omega-3 fatty acids into the food supply has been recognized by industry, which is already producing omega-3 enriched products.

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