Because blood concentrations of n-3 (or omega-3) fatty acids (FAs) (eicosapentaenoic and docosahexaenoic acids) are a strong reflection of dietary intake, it is proposed that a n-3 FA biomarker, the omega-3 index (erythrocyte eicosapentaenoic acid plus docosahexaenoic acid), be considered as a potential risk factor for coronary heart disease mortality, especially sudden cardiac death. The omega-3 index fulfills many of the requirements for a risk factor including consistent epidemiologic evidence, a plausible mechanism of action, a reproducible assay, independence from classic risk factors, modifiability, and, most important, the demonstration that raising levels will reduce risk for cardiac events. Measuring membrane concentrations of n-3 FAs is a rational approach to biostatus assessment as these FAs appear to exert their beneficial metabolic effects because of their actions in membranes. They alter membrane physical characteristics and the activity of membrane-bound proteins, and, once released by intracellular phospholipases from membrane stores, they can interact with ion channels, be converted into a wide variety of bioactive eicosanoids, and serve as ligands for several nuclear transcription factors, thereby altering gene expression. The omega-3 index compares very favorably with other risk factors for sudden cardiac death. Proposed omega-3 index risk zones are (in percentages of erythrocyte FAs): high risk, <4%; intermediate risk, 4-8%; and low risk, >8%. Before assessment of n-3 FA biostatus can be used in routine clinical evaluation of patients, standardized laboratory methods and quality control materials must become available.
