Eicosapentaenoic Acid and Docosahexaenoic Acid: Are They Different?
A reduction in heart rate by long-chain omega-3 fatty acids (n-3 LC-PUFAs) suggests a significant cardiac component associated with the antihypertensive effects possibly mediated by effects on autonomic nerve function or b-adrenoreceptor activity. We showed DHA, but not EPA, reduced 24-hour awake and asleep heart rate in overweight hyperlipidemic men.4 These effects were substantiated by others,8 including Woodman et al.2 in treated-hypertensive type 2 diabetic patients.In a short-term uncontrolled study in healthy individuals, von Schacky C et al.11 first showed differential effects of EPA and DHA on platelet responsiveness. Both reduced ex-vivo platelet aggregation to collagen but only DHA attenuated ADP-stimulated platelet aggregation.11 In the only controlled study in humans, we showed EPA did not alter collagen- or PAF-induced ex-vivo platelet aggregation in type 2 diabetic patients.1 However, DHA reduced collagen-induced aggregation and platelet thromboxane B2 (TXB2) release, but had no effect on PAF-induced aggregation.1 The reduction in platelet TXB2 following DHA may be due to competitive inhibition of cyclooxygenase, inhibition of TXA2 synthetase or inhibition of TXA2 receptor function. In contrast, Park et al.12showed that mean platelet volume, a marker of platelet activation, was decreased by EPA, but not DHA. Platelet count was also increased by EPA and not DHA.12 Disparate effects on glycemic control in type 2 diabetic patients likely relate to the dose of n-3 LC-PUFAs, oral diabetic medication, presence of obesity and/or insulin resistance, presence of other conditions such as hypertension, not controlling subjects’ diets and the duration of intervention. In dyslipidemic men, we showed a borderline significant increase in fasting glucose after 4g/day EPA but no change with DHA.3 Fasting serum insulin significantly increased after DHA, but not EPA, relative to placebo.3 In patients with type 2 diabetes, fasting glucose was increased following 4g/day EPA or DHA relative to control, but insulin, C-peptide and HbA1c, and insulin secretion and insulin sensitivity were unchanged.2 In vitro studies showed DHA, but not EPA, decreased pro-inflammatory cytokine expression, cell-adhesion molecules and monocyte adhesion to endothelial cells.13 The resolvins from EPA and DHA and protectins from DHA are potent agonists promoting active resolution of inflammation. They provide another example of different mechanisms for the anti-inflammatory effects of EPA and DHA.14 Concern that n-3 PUFAs increase lipid peroxidation and oxidative stress is unfounded. We showed EPA and DHA were equally effective in reducing plasma and urinary F2-isoprostanes.15,16 F2-isoprostanes derive from non-enzymatic free radical oxidation of arachidonic acid in membrane lipids and are the most reliable biomarkers of in vivo lipid peroxidative damage. Reduced F2-isoprostanes following EPA or DHA likely relate to decreased leukocyte activation and the immunomodulatory actions of n-3 PUFAs. EPA and DHA have many different yet complementary hemodynamic and anti-atherogenic properties. Human data suggest DHA may be more favorable in lowering blood pressure and improving vascular function, raising HDL-cholesterol and attenuating platelet function. However, EPA has important bioactive properties relevant to cardiovascular risk reduction. Further studies are needed to carefully assess the independent effects of EPA and DHA on other clinical and biochemical measures, and in other populations, before recommendations can be made with respect to the ratio of EPA to DHA in dietary supplements and food fortification. The greatest benefit on cardiovascular risk reduction is likely to be gained from a combination of both EPA and DHA. With the limited available data it is difficult to speculate what that proportion should be, but an approximate equal proportion of each would seem judicious. Exceptions may be situations such as in pregnancy-fetal development where DHA may be more important than EPA.
References1 Woodman RJ, Mori TA, Burke V, et al. Atherosclerosis 2003;166:85-93. 2 Woodman RJ, Mori TA, Burke V, et al. Am J Clin Nutr 2002;76:1007-1015. 3 Mori TA, Burke V, Puddey IB, et al. Am J Clin Nutr 2000;71:1085-1094. 4 Mori TA, Bao DQ, Burke V, et al. Hypertension 1999;34:253-260. 5 Grimsgaard S, Bonaa KH, Hansen JB, et al. Am J Clin Nutr 1997;66:649-659. 6 Nestel P, Shige H, Pomeroy S, et al. Am J Clin Nutr 2002;76:326-330. 7 Mclennan P, Howe P, Abeywardena M, et al. Eur J Pharmacol 1996;300:83-89. 8 Grimsgaard S, Bonaa KH, Hansen JB, et al. Am J Clin Nutr 1998;68:52-59. 9 Yamamoto H, Yoshimura H, Noma M, et al. Jap Circ J 1995;59:608-616. 10 Mori TA, Watts GF, Burke V, et al. Circulation 2000;102:1264-1269. 11 von Schacky C, Weber PC. J Clin Invest 1985;76:2446-2450. 12 Park Y, Harris W. Lipids 2002;37:941-9466. 13 De Caterina R, Liao JK, Libby P. Am J Clin Nutr 2000;71:213S-223S. 14 Serhan CN, Savill J. Nature Immunology 2005;6:1191-7. 15 Mori TA, Woodman RJ, Burke V, et al. Free Rad Biol Med 2003;35:772-781. 16 Mas E, Woodman RJ, Burke V, et al. Free Rad Res 2010 44:983-990.