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Annu. Rev. Nutr. 2004. 24:597–615 doi: 10.1146/annurev.nutr.24.012003.132106 Copyright c 2004 by Annual Reviews. All rights reserved

DIETARY n-6 AND n-3 FATTY ACID BALANCE AND CARDIOVASCULAR HEALTH
Vasuki Wijendran and K.C. Hayes
Foster Biomedical Research Lab, Brandeis University, Waltham, Massachusetts 02254; email: vwijen@brandeis.edu; kchayes@brandeis.edu

Key Words linoleic acid,linolenic acid, eicosapentaenoic acid, docoshexaenoic acid, coronary heart disease, cardiovascular risk factors I Abstract Epidemiological and clinical studies have established that the n-6 fatty acid, linoleic acid (LA), and the n-3 fatty acids, linolenic acid (LNA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) collectively protect against coronary heart disease (CHD). LA is the majordietary fatty acid regulating low-density lipoprotein (LDL)-C metabolism by downregulating LDL-C production and enhancing its clearance. Further, the available mass of LA is a critical factor determining the hyperlipemic effects of other dietary fat components, such as saturated and trans fatty acids, as well as cholesterol. By contrast, n-3 fatty acids, especially EPA and DHA, are potentantiarryhthmic agents. EPA and DHA also improve vascular endothelial function and help lower blood pressure, platelet sensitivity, and the serum triglyceride level. The distinct functions of these two families make the balance between dietary n-6 and n-3 fatty acids an important consideration influencing cardiovascular health. Based on published literature describing practical dietary intakes, we suggestthat consumption of ∼6% en LA, 0.75% en LNA, and 0.25% en EPA + DHA represents adequate and achievable intakes for most healthy adults. This corresponds to an n-6/n-3 ratio of ∼6:1. However, the absolute mass of essential fatty acids consumed, rather than their n-6/n-3 ratio, should be the first consideration when contemplating lifelong dietary habits affecting cardiovascular benefit from theirintake.

CONTENTS
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . POLYUNSATURATED FATTY ACIDS AND CORONARY HEART DISEASE RISK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Linoleic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . Alpha-Linolenic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Eicosapentaenoic Acid and Docosahexaenoic Acid . . . . . . . . . . . . . . . . . . . . . . . . . DIETARY n-6 AND n-3 PUFA INTAKE: MASS VERSUS RATIO . . . . . . . . . . . . . . . . SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . 598 598 598 600 602 604 609

0199-9885/04/0714-0597$14.00

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WIJENDRAN

HAYES

INTRODUCTION
Polyunsaturated fatty acids (PUFAs) of the n-6 and n-3 series are essential nutrients that exert an important influence on plasma lipids and serve cardiac and endothelial functions to impact the prevention and treatment of coronary heartdiseases (CHD). Both n-6 and n-3 PUFAs have distinct biological effects contributing to their cardioprotective action. While it is accepted that PUFAs of both series are dietary essentials, both the absolute intakes (g/d) and the n-6/n-3 ratio required to achieve optimal CHD health benefits are somewhat controversial, in part due to the failure to consider their intake in the context of total dailyfat and total daily PUFA (i.e., as a percent of energy) consumed by the population under study. This review critically evaluates the role of n-6 and n-3 PUFA on cardiovascular risk with consideration given to the “ideal” balance between the two series of fatty acids. A case is made that the absolute mass of the n-6 and n-3 PUFA consumed, rather than the ratio of n6/n-3 PUFA, should be the main...