Review Article| Volume 6, ISSUE 1, P5-18, January 2012

Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: A review

Published:November 04, 2011DOI:


      In this exploratory, hypothesis-generating literature review, we evaluated potentially differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and non-HDL-C in published studies of ω-3 fatty acid supplementation or prescription ω-3 fatty acid ethyl esters. Placebo-adjusted changes in mean lipid parameters were compared in randomized, controlled trials in subjects treated for ≥4 weeks with DHA or EPA. Of 22 studies identified, 6 compared DHA with EPA directly, 12 studied DHA alone (including 14 DHA–treated groups), and 4 examined EPA alone. In studies directly comparing EPA with DHA, a net increase in LDL-C of 3.3% was observed with DHA (DHA: +2.6%; EPA: −0.7%). In such head-to-head comparative studies, DHA treatment was associated with a net decrease in TG by 6.8% (DHA: −22.4%; EPA: −15.6%); a net increase in non-HDL-C by 1.7% (DHA: −1.2%; EPA −2.9%); and a net increase in HDL-C by 5.9% (DHA: +7.3%; EPA: +1.4%). Increases in LDL-C were also observed in 71% of DHA-alone groups [with demonstrated statistical significance (P < .05) in 67% (8 of 12) DHA-alone studies] but not in any EPA-alone studies. Changes in LDL-C significantly correlated with baseline TG for DHA-treated groups. The range of HDL-C increases documented in DHA-alone vs EPA-alone studies further supports the fact that HDL-C is increased more substantially by DHA than EPA. In total, these findings suggest that DHA-containing supplements or therapies were associated with more significant increases in LDL-C and HDL-C than were EPA-containing supplements or therapies. Future prospective, randomized trials are warranted to confirm these preliminary findings, determine the potential effects of these fatty acids on other clinical outcomes, and evaluate the generalizability of the data to larger and more heterogeneous patient populations.


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      • EPA and DHA: Distinct yet essential n-3 fatty acids
        Journal of Clinical LipidologyVol. 6Issue 5
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          In the article “The effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review,” Jacobson et al1 evaluated the differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on various lipid parameters, such as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and non-HDL-C. The premise of the review was to understand the relative and potentially disparate impacts that EPA and DHA have on these lipids, presumably to clear the way for use of isolated EPA in the population of patients with high levels of TG.
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