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Dose-Dependent Effects of Docosahexaenoic Acid Supplementation on Blood Lipids in Statin-Treated Hyperlipidaemic Subjects

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Lipids

Abstract

The objective of the study was to evaluate potential benefits of docosahexaenoic acid (DHA) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia. A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides (averaging 2.2 mmol/L) were randomised to take 4 g/day (n = 15) or 8 g/day (n = 15) of tuna oil or olive oil (placebo, n = 15) for 6 months. Plasma lipids, blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial. Plasma triglycerides were reduced 27% by 8 g/day DHA-rich fish oil (P < 0.05) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months. Even though total cholesterol was already well controlled by the statin treatment (mean initial level 4.5 mmol/L), there was a further dose-dependent reduction with fish oil supplementation (r = −0.344, P < 0.05). The extent of total cholesterol reduction correlated (r = −0.44) with the initial total cholesterol levels (P < 0.005). In the subset with initial plasma cholesterol above 3.8 mmol/L, plasma very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated and assayed for cholesterol and apolipoprotein B (apoB) at the commencement of the trial and at 3 months of intervention. Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL. There were no changes in IDL cholesterol, IDL apoB and high-density lipoprotein cholesterol. The results demonstrate that DHA-rich fish oil supplementation (2.16 g DHA/day) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months. Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia.

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Abbreviations

ANOVA:

Analysis of variance

CHD:

Coronary heart disease

DHA:

Docosahexaenoic acid

EPA:

Eicosapentaenoic acid

HDL:

High-density lipoprotein

HDL-C:

High-density lipoprotein cholesterol

IDL:

Intermediate-density lipoprotein

LDL:

Low-density lipoprotein

LDL-C:

Low-density lipoprotein cholesterol

PUFA:

Polyunsaturated fatty acids

VLDL:

Very low density lipoprotein

VLDL-C:

Very low density lipoprotein cholesterol

References

  1. Hopkins PN, Heiss G, Ellison RC, Province MA, Pankow JS, Eckfeldt JH, Hunt SC (2003) Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia: a case-control comparison from the National heart, lung, and blood Institute family heart study. Circulation 108:519–523

    Article  PubMed  Google Scholar 

  2. Lichtenstein AH, Ausman LM, Carrasco W, Jenner JL, Gualtieri LJ, Goldin BR, Ordovas JM, Schaefer EJ (1993) Effects of canola, corn, and olive oils on fasting and postprandial plasma lipoproteins in humans as part of a National Cholesterol Education Program step 2 diet. Arterioscler Thromb 13:1533–1542

    PubMed  CAS  Google Scholar 

  3. Shepherd J, Cobbe SM, Ford I, et al (1995) Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 333:1301–1307

    Article  PubMed  CAS  Google Scholar 

  4. Bruckert E, Baccara-Dinet M, McCoy F, Chapman J (2005) High prevalence of low HDL-cholesterol in a pan-European survey of 8,545 dyslipidaemic patients. Curr Med Res Opin 21:1927–1934

    Article  PubMed  CAS  Google Scholar 

  5. Howe PRC, Clifton PM, James MJ (1999) Equal antithrombotic and triglycerides-lowering effectiveness of eicosapentaenoic acid-rich and docosahexaenoic acid-rich fish oil supplements. Lipids 34:S307–S308

    Article  PubMed  CAS  Google Scholar 

  6. Mori TA, Beilin LJ (2001) Long-chain omega 3 fatty acids, blood lipids and cardiovascular risk reduction. Curr Opin Lipidol 12:11–17

    Article  PubMed  CAS  Google Scholar 

  7. Packard CJ, Caslake MJ (1997) Mixed hyperlipidaemia and lipid turnover. In: World of lipids. LibraPharm, Newbury

  8. Xydakis AM, Ballantyne CM (2002) Combination therapy for combined dyslipidemia. Am J Cardiol 90(Suppl):21K–29K

    Article  PubMed  CAS  Google Scholar 

  9. Contacos C, Barter PJ, Sullivan DR (1993) Effect of pravastatin and omega-3 fatty acids on plasma lipids and lipoproteins in patients with combined hyperlipidemia. Arterioscler Thromb 13:1755–1762

    PubMed  CAS  Google Scholar 

  10. Nordoy A, Bonaa KH, Nilsen H, Berge RK, Hansen JB, Ingebretsen OC (1998) Effects of simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia. J Intern Med 243:163–170

    Article  PubMed  CAS  Google Scholar 

  11. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M (2001) An omega-3 polyunsaturated fatty acid concentrate administered for 1 year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart 85:544–548

    Article  PubMed  CAS  Google Scholar 

  12. Chan DC, Watts GF, Mori TA, Barrett PHR, Beilin LJ, Redgrave TG (2002) Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity. Eur J Clin Nutr 32:429–436

    CAS  Google Scholar 

  13. Saklamaz A, Comlekci A, Temiz A, Caliskan S, Ceylan C, Alacacioglu A, Yesil S (2005) The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia. Metabolism 54:677–681

    Article  PubMed  CAS  Google Scholar 

  14. McKenney JM (2005) Efficacy and safety of rosuvastatin in treatment of dyslipidemia. Am J Health Syst Pharm 62:1033–1047

    PubMed  CAS  Google Scholar 

  15. Moses RG, Calvert D, Storlien LH (1996) Evaluation of the Accutrend GCT with respect to triglyceride monitoring. Diabetes Care 19:1305–1306

    Article  PubMed  CAS  Google Scholar 

  16. Warnick GR, Benderson J, Albers JJ (1982) Dextran sulphate–Mg2+ precipitation procedure for quantitation of high-density lipoprotein cholesterol. Clin Chem 28:1379–1388

    PubMed  CAS  Google Scholar 

  17. Freidewald WT, Levy RI, Fredickson DS (1972) Estimation of the concentration of LDL cholesterol in plasma without the use of the preparative ultracentrifuge. Clin Chem 18:499–502

    Google Scholar 

  18. Athyros VG, Papageorgiou AA, Hatzikonstandinou HA, Didangelos TP, Carina MV, Kranitsas DF, Kontopoulos AG (1997) Safety and efficacy of long-term statin–fibrate combinations in patients with refractory familial combined hyperlipidemia. Am J Cardiol 80:608–613

    Article  PubMed  CAS  Google Scholar 

  19. Pauciullo P, Borgnino C, Paoletti R, Mariani M, Mancini M (2000) Efficacy and safety of a combination of fluvastatin and benafibrate in patients with mixed hyperlipidemia (FACT study). Atherosclerosis 150:429–436

    Article  PubMed  CAS  Google Scholar 

  20. Pierce LR, Wysowski DK, Gross TP (1990) Myopathy and rabdomyolysis associated with lovastatin–gemfibrozil combination therapy. JAMA 264:71–75

    Article  PubMed  CAS  Google Scholar 

  21. Schectman G, Hiatt J (1996) Drug therapy for hypercholesterolemia in patients with cardiovascular disease: factors limiting achievement of lipid goals. Am J Med 100:197–204

    Article  PubMed  CAS  Google Scholar 

  22. Furberg CD, Pitt B (2001) Withdrawal of cerivastatin from the World market. Curr Control Trials Cardiovasc Med 2:205–207

    Article  PubMed  Google Scholar 

  23. Kashyap ML, McGovern ME, Berra K, Guyton JR, Kwiterovich PO Jr, Harper WL, Toth PD, Favrot LK, Kerzner B, Nash SD, Bays HE, Simmons PD (2002) Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. Am J Cardiol 89:672–678

    Article  PubMed  CAS  Google Scholar 

  24. Rader JI, Calvert RJ, Hathcock JN (1992) Hepatic toxicity of unmodified and time-release preparations of niacin. Am J Med 92:77–81

    Article  PubMed  CAS  Google Scholar 

  25. Norman DJ, Illingworth DR, Munson J, Hosenpud H (1988) Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin. N Engl J Med 318:46–47

    Article  PubMed  CAS  Google Scholar 

  26. Reaven P, Witzum JL (1988) Lovastatin, nicotinic acid, and rhabdomyolysis. Ann Intern Med 109:597–598

    PubMed  CAS  Google Scholar 

  27. Howe PRC, Lungershausen YK, Abbey M, Anderson JL, Ablett MB (1998) Effects of pravastatin and omega-3 fatty acids in peripheral arterial occlusive disease. In: 24th annual scientific meeting of the Australian Atherosclerosis Society, Cairns, abstract P10

  28. Nordoy A, Hansen JB, Brox J, Svensson B (2001) Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia. Nutr Metab Cardiovasc Dis 11:7–16

    PubMed  CAS  Google Scholar 

  29. Campos H, Genest JJ Jr, Blijlevens E, McNamara JR, Ordovas JM, Posner BM, Wilson PW, Castelli WP, Schaeffer EJ (1992) Low density lipoprotein particle size and coronary artery disease. Arterioscler Thromb 12:187–195

    PubMed  CAS  Google Scholar 

  30. Packard CJ (1996) LDL subfractions and atherogenicity: an hypothesis from the University of Glasgow. Curr Med Res Opin 13:379–390

    Article  PubMed  CAS  Google Scholar 

  31. Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB (2000) Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Am J Cardiol 86:46–52

    Article  PubMed  CAS  Google Scholar 

  32. Neil HA, Meijer GW, Roe LS (2001) Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. Atherosclerosis 156:329–337

    Article  PubMed  CAS  Google Scholar 

  33. Simons LA (2002) Additive effect of plant sterol-ester margarine and cerivastatin in lowering low-density lipoprotein cholesterol in primary hypercholesterolemia. Am J Cardiol 90:737–740

    Article  PubMed  CAS  Google Scholar 

  34. O’Neill FH, Brynes A, Mandeno R, Rendell N, Taylor G, Seed M, Thompson GR (2004) Comparison of the effects of dietary plant sterol and stanol esters on lipid metabolism. Nutr Metab Cardiovasc Dis 14:133–142

    Article  PubMed  CAS  Google Scholar 

  35. Thompson GR (2005) Additive effects of plant sterol and stanol esters to statin therapy. Am J Cardiol 96(Suppl):37D–39D

    Article  PubMed  CAS  Google Scholar 

  36. Harris JI, Hibbeln JR, Mackey RH, Muldoon MF (2004) Statin treatment alters serum n−3 and n−6 fatty acids in hypercholesterolemic patients. Prostaglandins Leukot Essent Fatty Acids 71:263–269

    Article  PubMed  CAS  Google Scholar 

  37. Rosenson RS, Tangney CC (1998) Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 279:1643–1650

    Article  PubMed  CAS  Google Scholar 

  38. Evans M, Rees A (2002) The myotoxicity of statins. Curr Opin Lipidol 13:415–420

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the study volunteers for their participation in the trial and Professor Dennis Calvert for the medical supervision of subject enrolment. The supply of placebo and DHA-rich fish oil capsules from Clover Corporation is gratefully acknowledged.

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Authors and Affiliations

  1. School of Health Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia

    Barbara J. Meyer

  2. Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway

    Tone Hammervold & Arild Chr. Rustan

  3. Nutritional Physiology Research Centre, School of Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia

    Peter R. C. Howe

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  1. Barbara J. Meyer
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  2. Tone Hammervold
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  4. Peter R. C. Howe
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Correspondence to Barbara J. Meyer.

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Meyer, B.J., Hammervold, T., Rustan, A.C. et al. Dose-Dependent Effects of Docosahexaenoic Acid Supplementation on Blood Lipids in Statin-Treated Hyperlipidaemic Subjects. Lipids 42, 109–115 (2007). https://doi.org/10.1007/s11745-006-3014-4

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  • DOI: https://doi.org/10.1007/s11745-006-3014-4

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