By Michael F. Richman, MD, FACS, FCCP
In 2008, I wrote a two-part series about Omega-3 Fatty Acids and discussed the most important components of O3FA’s — EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Almost daily, I discuss with my patients the fact that there are different amounts of EPA/DHA in every O3FA tablet, which makes it difficult to know how much EPA/DHA one is ingesting and if the levels are meeting the goals suggested by the American Heart Association. The AHA recommends O3FA intake in the form of routine fatty fish such as salmon for patients without Atherosclerotic Coronary Artery Disease (CAD), fish oil supplements in patients with CAD, and high-dose O3FA (about 4000 mg/day) in patients with high triglycerides. Until recently, it has just been a guessing game, but now doctors can use a new test called the HS-Omega-3 Index, which was developed by Dr. William Harris, to measure the amount of EPA and DHA within the membrane of a red blood cell.
The HS-Omega-3 Index has many features that qualify it as not only a biomarker of omega-3 intake, but also as a cardiovascular risk marker, and, most importantly, a risk factor and target for therapy. The optimal level of the HS-Omega-3 Index, based on the consensus of several studies, is currently 8% or greater, with a high-risk zone being less than 4% and an intermediate-risk zone of 4-8%. Ongoing research will further refine the target values for the HS-Omega-3 Index. At present, there is no compelling evidence for safety concerns at RBC omega-3 levels above the target level of 8%.
Few other cardiovascular biomarkers are as easily (and safely) modified as the HS-Omega-3 Index, and once modified, have as much potential to impact important clinical outcomes. If the HS-Omega-3 Index is ≥ 8% (low risk), there is no present need to change the diet or supplement with omega-3 fatty acids. If the Index is between 4.1-7.9% (intermediate risk range) and especially if it is ≤ 4% (high risk range), increasing the intake of EPA+DHA from oily fish and/or fish oil supplements (0.5-1g per day if intermediate; 1-2g per day if high risk) is advised. Retesting after 4-6 months is recommended for titrating the omega-3 dose because it takes about this long for membrane composition to reach a new steady state47.
Randomized controlled trials of Omega-3 FA have provided guidance for their use in clinical medicine. In the largest study to date (the Japan EPA Lipid Intervention Study, JELIS), 1.8g per day of EPA ethyl esters reduced the risk for major adverse cardiac events over 5 years in over 18,000 patients with high cholesterol, all of whom were taking statins. Sub-analyses of this study showed that treatment with EPA reduced risk in patients with pre-existing coronary disease, impaired glucose metabolism, peripheral artery disease, a history of stroke, and with the abnormal lipids characteristic of the metabolic syndrome. At present, the substantial evidence suggests that correcting an omega-3 insufficiency (i.e., increasing the omega-3 index) reduces coronary heart disease risk and can be accomplished quickly, safely, and cheaply. Of all the coronary heart disease risk factors currently known, none is as amenable to correction nor is as potentially impactful once corrected as the omega-3 index.