Effect of Dietary Linoleic Acid on Markers of Inflammation in Healthy Persons: A Systematic Review of Randomized Controlled Trials

The majority of evidence suggests that n-6 polyunsaturated fatty acids, including linoleic acid (LA), reduce the risk of cardiovascular disease as reflected by current dietary recommendations. However, concern has been expressed that a high intake of dietary n-6 polyunsaturated fatty acid contributes to excess chronic inflammation, primarily by prompting the synthesis of proinflammatory eicosanoids derived from arachidonic acid and/or inhibiting the synthesis of anti-inflammatory eicosanoids from eicosapentaenoic and/or docosahexaenoic acids. A systematic review of randomized controlled trials that permitted the assessment of dietary LA on biologic markers of chronic inflammation among healthy noninfant populations was conducted to examine this concern. A search of the English- and non-English-language literature using MEDLINE, the Cochrane Controlled Trials Register, and EMBASE was conducted to identify relevant articles. Fifteen studies (eight parallel and seven crossover) met inclusion criteria. None of the studies reported significant findings for a wide variety of inflammatory markers, including C-reactive protein, fibrinogen, plasminogen activator inhibitor type 1, cytokines, soluble vascular adhesion molecules, or tumor necrosis factor-α. The only significant outcome measures reported for higher LA intakes were greater excretion of prostaglandin E2 and lower excretion of 2,3-dinor-thromboxane B2 in one study and higher excretion of tetranorprostanedioic acid in another. However, the authors of those studies both observed that these effects were not an indication of increased inflammation. We conclude that virtually no evidence is available from randomized, controlled intervention studies among healthy, noninfant human beings to show that addition of LA to the diet increases the concentration of inflammatory markers.