Dietary Fats Omega-6 and Omega-3: Impact Your Inflammation Gene Machine
Background: Inflammatory diseases are on the rise. It is estimated that within the next two decades, more than one in three Americans will have an inflammatory disease, which include heart disease, asthma and rheumatoid arthritis. Many scientists believe this upward trend is due to the dramatic rise in dietary omega-6 polyunsaturated fats, which outnumber omega-3 fats, by 10 to 1, in the typical American diet. In contrast, our hunter-gatherer ancestors consumed an estimated one-to-one balance of these fats.
Studies indicated that eating excess dietary omega-6 fat, increases the omega-6 derived eicosanoids, (which include leukotrienes); which in turn, may lead to a systemic pro-inflammatory state in the body. For example, when the LOX enzyme acts on the omega-6 fatty acid, arachidonic acid, it creates the potent leukotriene, LTB4, (which is the compound implicated in asthma and atherosclerosis). Yet, if this enzyme acts on the omega-3 fatty acid, EPA, it creates leukotriene compounds that are 10 to 100-fold less potent.
Additionally, animal studies indicate that polyunsaturated fatty acids modulate the genes effecting inflammation. But whether that holds true for people, has been unknown, until this study.
Study: Healthy volunteers (27), were fed a controlled background diet for five weeks. After the first week, they were given supplemental fish oil and borage oil for a four-week period, which provided 775 mg EPA and 831 mg GLA. Then on the sixth and seventh weeks, the volunteers resumed their normal diet, comprising a two-week washout-out period. Weekly blood samples were evaluated for: fatty acid distribution in serum and neutrophils, leukotriene metabolites, cytokines, and the genes influencing eicosanoid and cytokine formation.
Results: In the neutrophil cells, there was a marked 40% reduction in the omega-6 to omega-3 fatty acid ratio, which resulted in a 55% decrease of LTB4 production in the “responders” group, as shown below:
There was a significant decrease in pro-inflammatory cytokines. The researchers noted their surprise on finding a marked decrease in the expression of a key regulatory compound, P13K, which influences eicosanoid and cytokine formation, cell growth, cell survival and inflammation.
Conclusion: Altering the omega-6 and omega-3 polyunsaturated fatty acids in healthy volunteers, resulted in a markedly changed fatty acid composition in neutrophils, which inhibited their capacity to generate leukotriene LTB4, a potent biomarker of inflammation. Most notably, polyunsaturated fatty acids impacted the expression of proinflammatory cytokine genes and signal transduction genes, with a decrease in several proinflammatory cytokines.
Quote: “This report demonstrates, for the first time in humans, that the expression of an early step (P13K) in signal transduction, as well as several important downstream effectors are significantly reduced by altering ingestion of polyunsaturated fatty acids to shift circulating omega-6 to omega-3 ratios.”
Comments: Attention to the background diet is often a missing design element in supplementation studies, which is necessary to observe consistent changes in cellular fatty acid distribution.
This study not only controlled the background diet, it included an evaluation of the transient effect of diet on cellular levels of fatty acid composition; which was elegantly demonstrated, by adding a two-week period of normal eating (weeks 6 and 7). Notably, the ratio of cellular arachidonic acid to EPA decreased by 75%, during the “study period”, but increased to near the baseline levels, after the volunteers returned to their normal eating patterns. This was also true for LTB4 levels.
Study:
Weaver KL, Ivester P, Seeds M, Case LD, Arm JP, and Chilton FH.
Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans J Biol Chem. 2009 Jun 5;284(23):15400-7[abstract]
Posted by Evelyn Tribole MSRD at July 20, 2009 9:43 AM 
Categories: Arachidonic Acid,LOX,asthma,2009 Studies,omega-6/omega-3 Ratio,Diet,polyunsaturated fatty acids,fish oil,Omega-6 Fat,EPA,Biomarkers,Abstract
Categories: Arachidonic Acid,LOX,asthma,2009 Studies,omega-6/omega-3 Ratio,Diet,polyunsaturated fatty acids,fish oil,Omega-6 Fat,EPA,Biomarkers,Abstract
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