Publications by Dr. William Harris

Prev Med. 2004 Jul;39(1):212-20.


The Omega-3 Index: a new risk factor for death from coronary heart disease?


Harris WS, Von Schacky C.


1Lipid and Diabetes Research Center, Mid America Heart Institute of Saint Luke's Hospital, University of Missouri-KC School of Medicine, Kansas City, MO 64111, USA.




Low intakes or blood levels of eicosapentaenoic and docosahexaenoic acids (EPA + DHA) are independently associated with increased risk of death from coronary heart disease (CHD). In randomized secondary prevention trials, fish or fish oil have been demonstrated to reduce total and CHD mortality at intakes of about 1 g/day. Red blood cell (RBC) fatty acid (FA) composition reflects long-term intake of EPA + DHA. We propose that the RBC EPA + DHA (hereafter called the Omega-3 Index) be considered a new risk factor for death from CHD.


We conducted clinical and laboratory experiments to generate data necessary for the validation of the Omega-3 Index as a CHD risk predictor. The relationship between this putative marker and risk for CHD death, especially sudden cardiac death (SCD), was then evaluated in several published primary and secondary prevention studies.


The Omega-3 Index was inversely associated with risk for CHD mortality. An Omega-3 Index of > or = 8% was associated with the greatest cardioprotection, whereas an index of < or = 4% was associated with the least.


The Omega-3 Index may represent a novel, physiologically relevant, easily modified, independent, and graded risk factor for death from CHD that could have significant clinical utility.

Copyright 2004 The Institute for Cancer Prevention and Elsevier Inc.




Pharmacol Res. 2007 Mar;55(3):217-23. Epub 2007 Jan 25.


Omega-3 fatty acids and cardiovascular disease: a case for omega-3 index as a new risk factor.


Harris, W. S.


Nutrition and Metabolic Disease Research Institute, Sanford Research/USD, Sanford School of Medicine of the University of South Dakota, 1400 West 22nd Street, Sioux Falls, SD 57105, USA.



The omega-3 fatty acids (FAs) found in fish and fish oils (eicosapentaenoic and docosahexaenoic acids, EPA and DHA) have been reported to have a variety of beneficial effects in cardiovascular diseases. Ecological and prospective cohort studies as well as randomized, controlled trials have supported the view that the effects of these FAs are clinically relevant. They operate via several mechanisms, all beginning with the incorporation of EPA and DHA into cell membranes. From here, these omega-3 FA alter membrane physical characteristics and the activity of membrane-bound proteins, and once released by intracellular phospholipases, 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. In as much as blood levels are a strong reflection of dietary intake, it is proposed that an omega-3 FA biomarker, the omega-3 index (erythrocyte EPA+DHA) be considered at least a marker, if not a risk factor, for coronary heart disease, especially sudden cardiac death. The omega-3 index fulfils many of the requirements for a risk factor including consistent epidemiological evidence, a plausible mechanism of action, a reproducible assay, independence from classical risk factors, modifiability, and most importantly, the demonstration that raising tissue levels will reduce risk for cardiac events. For these and a number of other reasons, the omega-3 index compares very favourably with other risk factors for sudden cardiac death.