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Importance of maintaining a low omega–6/omega–3 ratio for reducing inflammation
  1. James J DiNicolantonio and
  2. James H O’Keefe
  1. Saint Luke’s Mid America Heart Institute, Kansas, Missouri, USA
  1. Correspondence to Dr James J DiNicolantonio; jjdinicol{at}

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The consumption of seed oils high in the omega-6 polyunsaturated fat (PUFA) linoleic acid (LA) contributes to low-grade inflammation, oxidative stress, endothelial dysfunction and atherosclerosis.1 Moreover, dietary LA significantly increases cyclooxygenase-2 (COX-2) expression in the aorta,2 converting arachidonic acid (AA) to proinflammatory eicosanoids. This may explain why increasing LA intake can actually lower AA levels due to an increased breakdown into harmful proinflammatory metabolites. Additionally, there is an AA-independent pathway of inflammation promoted by the intake of omega-6 seed oils such as increased production of oxidised linoleic acid metabolites (OXLAMs) and proinflammatory LA CYP-eicosanoids.3–5 OXLAMs formed from LA activate NF-kB and increase proinflammatory cytokines, endothelial adhesion molecules, as well as chemokines, all of which are paramount in the formation of atherosclerosis.5–8 LA also induces an inflammatory environment in endothelial cells that may increase the risk of coronary heart disease (CHD).8 OXLAMs are found at a 50-fold higher concentration in plasma than AA metabolites, suggesting that they are more consequential in CHD and other chronic diseases,2 3 9 and lowering dietary LA reduces OXLAMs in the body.3

By inhibiting COXs and lipoxygenases (LOXs), marine omega-3s can reduce inflammation caused by the metabolism of AA. Indeed, compared with high-oleic sunflower oil (3.5 g/day), fish oil (3.5 g/day) reduces acute phase reactants (haptoglobin precursor, haemopexin, alpha-1-antitrypsin precursor and serum amyloid P component). The authors concluded, ‘The alterations in serum proteins… imply that fish oil activates anti-inflammatory mechanisms believed to impede the early onset of CHD’.10 In human atherosclerotic lesions, as the atherosclerotic lesion becomes more advanced, the ratio between oxidised LA and unoxidised LA increases.11 Moreover, rats fed LA have a significant increase in tumour necrosis factor (TNF)-alpha (p<0.05) in plasma, and higher levels of vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) …

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