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The role of dietary n-6 fatty acids in the prevention of cardiovascular disease

Willett, Walter C

Journal of Cardiovascular Medicine: September 2007 - Volume 8 - Issue - p S42–S45
doi: 10.2459/01.JCM.0000289275.72556.13
Original articles

n-6 Fatty acids, like n-3 fatty acids, play essential roles in many biological functions. Because n-6 fatty acids are the precursors of proinflammatory eicosanoids, higher intakes have been suggested to be detrimental, and the ratio of n-6 to n-3 fatty acids has been suggested by some to be particularly important. However, this hypothesis is based on minimal evidence, and in humans higher intakes of n-6 fatty acids have not been associated with elevated levels of inflammatory markers.

n-6 Fatty acids have long been known to reduce serum total and low-density lipoprotein cholesterol, and increases in polyunsaturated fat intake, mostly as n-6 fatty acids, were a cornerstone of dietary advice during the 1960s and 1970s. In the United States, for example, intake of n-6 fatty acids doubled and coronary heart disease (CHD) mortality fell by 50% over a period of several decades. In a series of relatively small, older randomized trials, in which intakes of polyunsaturated fat were increased (even up to 20% of calories), rates of CHD were generally reduced. In a more recent detailed examination of fatty acid intake within the Nurses' Health Study, greater intake of linoleic acid, up to about 8% of energy, has been strongly related to lower incidence of myocardial infarction or CHD death. Because n-3 fatty acids were also related inversely to risk of CHD, the ratio was unrelated to risk. n-6 Fatty acids reduce insulin resistance, probably by acting as a ligand for peroxisome proliferator-activated receptors-γ, and intakes have been inversely related to risk of type 2 diabetes.

Adequate intakes of both n-6 and n-3 fatty acids are essential for good health and low rates of cardiovascular disease and type 2 diabetes, but the ratio of these fatty acids is not useful. Reductions of linoleic acid to “improve” this ratio would likely increase rates of cardiovascular disease and diabetes.

Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA

Correspondence to Prof Walter C. Willett, Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA Tel: +617 4324680; fax: +617 4320464; e-mail:

The author reports no conflicts of interest.

© 2007 Italian Federation of Cardiology. All rights reserved.