It has long been “received wisdom” that patients who carry 1 or 2 copies of the apoE4 gene “do not benefit” from taking omega-3 fatty acids. This view was based on a few small studies that showed trends for LDL-C to increase more in apoE4 carriers than noncarriers when taking fish oil supplements. This dogma had a chilling effect on the use of omega-3 fatty acids in this patient group, which constitutes about 30% of Americans. We undertook a study based on over 130,000 patient samples analyzed at HDL, Inc. We hypothesized that patients with a higher Omega-3 Index (a valid biomarker of omega-3 intake) who were also apoE4 carriers would have a higher LDL-C than noncarriers with the same high Omega-3 Index. However, we found that the relationship between LDL-C and the Omega-3 Index was not different between carriers and noncarriers. In other words, we found no evidence that there was a differential effect of omega-3 fatty acids on lipids as a function of apoE4 status. In any event, the dogma was likely flawed from the outset by defining “benefit” only in terms of effects on LDL-C. The anti-atherogenic effects of omega-3 are largely mediated by nonlipoprotein-based mechanisms… so even if LDL-C (or even LDL-P) was a little higher in apoE4 carriers on fish oil than noncarriers, that would not mean that omega-3 fatty acids were of “no benefit” to those patients. Further, apoE4 patients are not only at increased risk for developing CHD than non-carriers, they are also at higher risk for Alzheimer’s disease, and new data are now showing that omega-3 fatty acids may be able to slow the development of both diseases. Thus, if anybody should be treated to target Omega-3 Index levels of 8% or more, it is the apoE4 carrier.
Taking a wider view, it is well known that ε4 patients are at higher risk for CHD [5, 17] and for Alzheimer’s disease . Even if the efficacy of fish oil supplements as treatments for CHD is in question [23, 24], several studies have shown that higher omega-3 fatty acid blood levels are associated with decreased risk for all-cause mortality [25–28] and dementia . Direct consumption of EPA and DHA (whether from fish oil supplements or oily fish) is by far the most important determinant of the Omega-3 Index [30–33]. Their safety profile is strong , and thus, their risk/benefit ratio is favorable. Finally, because ε4 carriers may require higher doses of EPA+DHA to raise the Omega-3 Index (as suggested in some [35, 36] but not other  studies), patients carrying this allele may be the most likely to benefit from an increased omega-3 fatty acid intake.
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