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Current Atherosclerosis Reports

, Volume 13, Issue 6, pp 474–483 | Cite as

Effects of Eicosapentaenoic Acid Versus Docosahexaenoic Acid on Serum Lipids: A Systematic Review and Meta-Analysis

  • Melissa Y. WeiEmail author
  • Terry A. JacobsonEmail author
Nutrition (William S. Harris, Section Editor)

Abstract

Omega-3 fatty acid supplements containing both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to reduce triglycerides but also increase low-density lipoprotein (LDL). Whether EPA or DHA given as monotherapy has differential effects on serum lipoproteins has not been systematically evaluated. We performed a meta-analysis of randomized placebo-controlled trials of monotherapy with EPA (n = 10), DHA (n = 17), or EPA versus DHA (n = 6). Compared with placebo, DHA raised LDL 7.23 mg/dL (95% CI, 3.98–10.5) whereas EPA non-significantly reduced LDL. In direct comparison studies, DHA raised LDL 4.63 mg/dL (95% CI, 2.15–7.10) more than EPA. Both EPA and DHA reduced triglycerides, with a greater reduction by DHA in direct comparison studies. DHA also raised high-density lipoprotein (4.49 mg/dL; 95% CI, 3.50–5.48) compared with placebo, whereas EPA did not. Although EPA and DHA both reduce triglycerides, they have divergent effects on LDL and high-density lipoprotein. Further research is needed to elucidate the mechanisms and significance of these differences.

Keywords

Omega-3 fatty acid Eicosapentaenoic acid Docosahexaenoic acid High-density lipoprotein cholesterol Low-density lipoprotein cholesterol Triglyceride Cardiovascular disease Systematic review Meta-analysis 

Abbreviations

CETP

Cholesteryl ester transfer protein

CI

Confidence interval

COMBOS

Combination of Prescription Omega-3 with Simvastatin

df

Degrees of freedom

DHA

Docosahexaenoic acid

EPA

Eicosapentaenoic acid

HDL

High-density lipoprotein cholesterol

JELIS

Japanese EPA Lipid Intervention Study

LDL

Low-density lipoprotein cholesterol

PPAR

Peroxisome proliferator-activator receptors

Notes

Disclosure

M.Y. Wei: none; T.A. Jacobson is a consultant for GlaxoSmithKline and Amarin.

References

Papers of particular interest, published recently, have been highlighted as • Of importance •• Of most importance

  1. 1.
    Manninen V, Tenkanen L, Koskinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment. Circulation. 1992;85:37–45.PubMedGoogle Scholar
  2. 2.
    Ballantyne CM, Olsson AG, Cook TJ. Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S. Circulation. 2001;104:3046–51.PubMedCrossRefGoogle Scholar
  3. 3.
    Tirosh A, Rudich A, Shochat T. Changes in triglyceride levels and risk for coronary heart disease in young men. Ann Intern Med. 2007;147:377–85.PubMedGoogle Scholar
  4. 4.
    Carroll MD, Lacher DA, Sorlie PD, et al. Trends in serum lipids and lipoproteins of adults, 1960–2002. JAMA. 2005;294:1773–81.PubMedCrossRefGoogle Scholar
  5. 5.
    Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 Suppl):1645S–54S.PubMedGoogle Scholar
  6. 6.
    Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747–57.PubMedCrossRefGoogle Scholar
  7. 7.
    von Schacky C, Harris WS. Cardiovascular benefits of omega-3 fatty acids. Cardiovasc Res. 2007;73:310–5.CrossRefGoogle Scholar
  8. 8.
    •• Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123:2292–333. This article discusses the current American Heart Association recommendations for EPA plus DHA supplementation and the clinical evidence and potential mechanisms supporting these recommendations. PubMedCrossRefGoogle Scholar
  9. 9.
    Harris WS, Miller M, Tighe AP, Davidson MH, Schaefer EJ. Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis. 2008;197:12–24.PubMedCrossRefGoogle Scholar
  10. 10.
    Kliewer SA, Sundseth SS, Jones SA, et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci USA. 1997;94:4318–23.PubMedCrossRefGoogle Scholar
  11. 11.
    Xu HE, Lambert MH, Montana VG, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 1999;3:397–403.PubMedCrossRefGoogle Scholar
  12. 12.
    Eslick GD, Howe PR, Smith C, et al. Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol. 2009;136:4–16.PubMedCrossRefGoogle Scholar
  13. 13.
    Davidson MH, Stein EA, Bays HE, et al. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354–67.PubMedCrossRefGoogle Scholar
  14. 14.
    • Maki KC, Dicklin MR, Davidson MH, et al. Baseline lipoprotein lipids and low-density lipoprotein cholesterol response to prescription omega-3 acid ethyl ester added to Simvastatin therapy. Am J Cardiol. 2010;105:1409–12. This post-hoc analysis of the COMBOS trial identifies subgroups of participants for which increased LDL occurs with omega-3 fatty acid ethyl ester plus simvastatin therapy. PubMedCrossRefGoogle Scholar
  15. 15.
    Tanaka K, Ishikawa Y, Yokoyama M, et al. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke. 2008;39:2052–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Normand SL. Meta-analysis: formulating, evaluating, combining, and reporting. Stat Med. 1999;18:321–59.PubMedCrossRefGoogle Scholar
  17. 17.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.PubMedCrossRefGoogle Scholar
  18. 18.
    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.PubMedCrossRefGoogle Scholar
  19. 19.
    Jacobson T, Soni P, Glickstein S, et al. Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol: a critical review [abstract]. J Clin Lipidol. 2011;5:200–1.CrossRefGoogle Scholar
  20. 20.
    Ando M, Sanaka T, Nihei H. Eicosapentanoic acid reduces plasma levels of remnant lipoproteins and prevents in vivo peroxidation of LDL in dialysis patients. J Am Soc Nephrol. 1999;10:2177–84.PubMedGoogle Scholar
  21. 21.
    Satoh N, Shimatsu A, Kotani K, et al. Purified eicosapentaenoic acid reduces small dense LDL, remnant lipoprotein particles, and C-reactive protein in metabolic syndrome. Diabetes Care. 2007;30:144–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Egert S, Kannenberg F, Somoza V, et al. Dietary alphalinolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans. J Nutr. 2009;139:861–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Kurabayashi T, Okada M, Tanaka K. Eicosapentaenoic acid effect on hyperlipidemia in menopausal Japanese women. Obstet Gynecol. 2000;96:521–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Grimsgaard S, Bonaa KH, Hansen JB, et al. Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids. Am J Clin Nutr. 1997;66:649–59.PubMedGoogle Scholar
  25. 25.
    Park Y, Harris WS. Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance. J Lipid Res. 2003;44:455–63.PubMedCrossRefGoogle Scholar
  26. 26.
    Mori TA, Woodman RJ. The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans. Curr Opin Clin Nutr Metab Care. 2006;9:95–104.PubMedCrossRefGoogle Scholar
  27. 27.
    Nestel P, Shige H, Pomeroy S, et al. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am J Clin Nutr. 2002;76:326–30.PubMedGoogle Scholar
  28. 28.
    Woodman RJ, Mori TA, Burke V, et al. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr. 2002;76:1007–15.PubMedGoogle Scholar
  29. 29.
    Conquer JA, Holub BJ. Effect of supplementation with different doses of DHA on the levels of circulating DHA as non-esterified fatty acid in subjects of Asian Indian background. J Lipid Res. 1998;39:286–92.PubMedGoogle Scholar
  30. 30.
    Kelley DS, Siegel D, Vemuri M, et al. Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men. Am J Clin Nutr. 2007;86:324–33.PubMedGoogle Scholar
  31. 31.
    Stark KD, Holub BJ. Differential eicosapentaenoic acid elevations and altered cardiovascular disease risk factor responses after supplementation with docosahexaenoic acid in postmenopausal women receiving and not receiving hormone replacement therapy. Am J Clin Nutr. 2004;79:765–73.PubMedGoogle Scholar
  32. 32.
    Mori TA, Burke V, Puddey IB, et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr. 2000;71:1085–94.PubMedGoogle Scholar
  33. 33.
    Sanders TA, Gleason K, Griffin B, et al. Influence of an algal triacylglycerol containing docosahexaenoic acid (22:6 n-3) and docosapentaenoic acid (22:5 n-6) oncardiovascular risk factors in healthy men and women. Br J Nutr. 2006;95:525–31.PubMedCrossRefGoogle Scholar
  34. 34.
    Theobald HE, Chowienczyk PJ, Whittall R, et al. LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and women. Am J Clin Nutr. 2004;79:558–63.PubMedGoogle Scholar
  35. 35.
    Maki KC, Van Elswyk ME, McCarthy D, et al. Lipid responses to a dietary docosahexaenoic acid supplement in men and women with below average levels of high density lipoprotein cholesterol. J Am Coll Nutr. 2005;24:189–99.PubMedGoogle Scholar
  36. 36.
    Geppert J, Kraft V, Demmelmair H, et al. Microalgal docosahexaenoic acid decreases plasma triacylglycerol in normolipidaemic vegetarians: a randomised trial. Br J Nutr. 2006;95:779–86.PubMedCrossRefGoogle Scholar
  37. 37.
    Conquer JA, Holub BJ. Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. J Nutr. 1996;126:3032–9.PubMedGoogle Scholar
  38. 38.
    Agren JJ, Hänninen O, Julkunen A, et al. Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels. Eur J Clin Nutr. 1996;50:765–71.PubMedGoogle Scholar
  39. 39.
    Wu WH, Lu SC, Wang TF, et al. Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women. Eur J Clin Nutr. 2006;60:386–92.PubMedCrossRefGoogle Scholar
  40. 40.
    Schaefer EJ, Asztalos IB, Gleason JA, et al. Effects of eicosapentaenoic acid, docosahexaenoic acid, and olive oil on cardiovascular disease risk factors [abstract]. Circulation. 2010;122:A20007.Google Scholar
  41. 41.
    •• Bays HE, Ballantyne CM, Kastelein JJ, et al. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels: the MARINE trial. Am J Card. 2011;In press. This large placebo-controlled trial of EPA demonstrates a reduction in triglycerides without raising LDL in participants with very high triglyceride levels. Google Scholar
  42. 42.
    Hirano R, Igarashi O, Kondo K, et al. Regulation by long-chain fatty acids of the expression of cholesteryl ester transfer protein in HepG2 cells. Lipids. 2001;36:401–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of MedicineEmory University School of MedicineAtlantaGeorgia
  2. 2.Office of Health Promotion and Disease Prevention, Department of MedicineEmory UniversityAtlantaUSA

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