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EPA and DHA: Distinct yet essential n-3 fatty acids
Journal of Clinical Lipidology (2012) 6, 477–479
Letters to the Editor
EPA and DHA: Distinct yet essential n-3 fatty acids 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), highdensity 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. In this review, the authors evaluated results of 22 highly divergent clinical trials with the worthy intent of shedding light on this important matter. What did they find? Succinctly stated, EPA increased LDL-C to a lesser extent than DHA and decreased nonHDL-C to a greater extent than DHA. DHA increased HDL-C to a greater extent than EPA and decreased TG to a greater extent than EPA. Lipoproteins were not assessed, yet lipid specialists understand that lowering TG and raising HDL (the result of DHA supplementation) is typically accompanied by a concomitant decrease in apolipoprotein B (apoB) or low-density lipoprotein particles. We also acknowledge that lower levels of apoB and LDL-P are associated with diminished cardiovascular disease outcomes. In view of these verities, I am left wondering why the authors focused on the miniscule difference in the LDL-C and non-HDL-C effects of these n-3 fatty acids. N-3 fatty acids have many diverse effects but only one prescription indication, that is, to lower the levels of TG. In view of that fact, why not focus on the superior effect of DHA in lowering TG? Why also downplay the greater HDL-C2increasing effect of DHA? It is true that our guidelines regard LDL-C as the primary target in lipid management, but the American College of Cardiology and American Diabetes Association, as well as the National Lipid Association, have clearly acknowledged the importance of evaluating and managing LDL-P or apoB in dyslipidemic patients, the very subjects of this review. In addition, it is highly likely from the data acquired in this review that the n-3 fatty acid with the better apoB- and
LDL-P2lowering effect is DHA, not EPA. There are other elements of the review that merit consideration: the studies were small and tended to be short; the non-HDL effect of the fatty acids were described in terms of a ‘‘net increase’’ with DHA, when in fact there was an ‘‘absolute decrease’’; the formulations of DHA were quite disparate, possessing various and divers fatty acids with their own potential impacts on the lipid parameters assessed. Beyond all these issues, it is vital for us to remember that EPA and DHA have effects that span well beyond lipids. Many of these properties may in fact be far more consequential than the lipid effects evaluated. Thus, we must be cautious not to condemn either EPA or DHA because of isolated differences, lipid or otherwise, that we may discover. They are both likely to impart a wide array of therapeutic advantages for us all. Seth J. Baum, MD, FACC, FAHA, FACPM, FNLA Boca Raton, FL, USA http://dx.doi.org/10.1016/j.jacl.2012.04.001
Reference 1. Jacobson TA, Glickstein SB, Rowe JD, et al. The effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review. J Clin Lipidol. 2012;6:5–18.
Authors’ reply to commentary entitled ‘‘EPA and DHA: Distinct yet essential n-3 fatty acids’’ We would like to thank Dr. Baum for his interest in, and close reading of, our recent review article.1 Many of the issues that he rightly identifies were acknowledged as limitations in our article. However, we would like to reply to some of his more salient points that perhaps were not as thoroughly addressed. As underscored more than once in the article, this review was of an exploratory, hypothesis-generating nature and was conducted in part to ascertain and document any differences between docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in their effects on low-density lipoprotein cholesterol (LDL-C) and selected other lipids and lipoproteins.
1933-2874/$ - see front matter Ó 2012 National Lipid Association. All rights reserved.
Letters to the Editor
EPA and DHA: Distinct yet essential n-3 fatty acids 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), highdensity 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. In this review, the authors evaluated results of 22 highly divergent clinical trials with the worthy intent of shedding light on this important matter. What did they find? Succinctly stated, EPA increased LDL-C to a lesser extent than DHA and decreased nonHDL-C to a greater extent than DHA. DHA increased HDL-C to a greater extent than EPA and decreased TG to a greater extent than EPA. Lipoproteins were not assessed, yet lipid specialists understand that lowering TG and raising HDL (the result of DHA supplementation) is typically accompanied by a concomitant decrease in apolipoprotein B (apoB) or low-density lipoprotein particles. We also acknowledge that lower levels of apoB and LDL-P are associated with diminished cardiovascular disease outcomes. In view of these verities, I am left wondering why the authors focused on the miniscule difference in the LDL-C and non-HDL-C effects of these n-3 fatty acids. N-3 fatty acids have many diverse effects but only one prescription indication, that is, to lower the levels of TG. In view of that fact, why not focus on the superior effect of DHA in lowering TG? Why also downplay the greater HDL-C2increasing effect of DHA? It is true that our guidelines regard LDL-C as the primary target in lipid management, but the American College of Cardiology and American Diabetes Association, as well as the National Lipid Association, have clearly acknowledged the importance of evaluating and managing LDL-P or apoB in dyslipidemic patients, the very subjects of this review. In addition, it is highly likely from the data acquired in this review that the n-3 fatty acid with the better apoB- and
LDL-P2lowering effect is DHA, not EPA. There are other elements of the review that merit consideration: the studies were small and tended to be short; the non-HDL effect of the fatty acids were described in terms of a ‘‘net increase’’ with DHA, when in fact there was an ‘‘absolute decrease’’; the formulations of DHA were quite disparate, possessing various and divers fatty acids with their own potential impacts on the lipid parameters assessed. Beyond all these issues, it is vital for us to remember that EPA and DHA have effects that span well beyond lipids. Many of these properties may in fact be far more consequential than the lipid effects evaluated. Thus, we must be cautious not to condemn either EPA or DHA because of isolated differences, lipid or otherwise, that we may discover. They are both likely to impart a wide array of therapeutic advantages for us all. Seth J. Baum, MD, FACC, FAHA, FACPM, FNLA Boca Raton, FL, USA http://dx.doi.org/10.1016/j.jacl.2012.04.001
Reference 1. Jacobson TA, Glickstein SB, Rowe JD, et al. The effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review. J Clin Lipidol. 2012;6:5–18.
Authors’ reply to commentary entitled ‘‘EPA and DHA: Distinct yet essential n-3 fatty acids’’ We would like to thank Dr. Baum for his interest in, and close reading of, our recent review article.1 Many of the issues that he rightly identifies were acknowledged as limitations in our article. However, we would like to reply to some of his more salient points that perhaps were not as thoroughly addressed. As underscored more than once in the article, this review was of an exploratory, hypothesis-generating nature and was conducted in part to ascertain and document any differences between docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in their effects on low-density lipoprotein cholesterol (LDL-C) and selected other lipids and lipoproteins.
1933-2874/$ - see front matter Ó 2012 National Lipid Association. All rights reserved.