Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu / Tam, Joseph


CiteScore 2016: 1.01

SCImago Journal Rank (SJR) 2016: 0.349
Source Normalized Impact per Paper (SNIP) 2016: 0.495

Online
ISSN
2191-0286
See all formats and pricing
More options …
Volume 28, Issue 4

Issues

Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia

Štefan TóthORCID iD: http://orcid.org/0000-0002-9789-3305 / Matej Šajty
  • First Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Košice, Slovakia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Tímea Pekárová
  • First Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Košice, Slovakia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Adil Mughees
  • First Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Košice, Slovakia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Peter Štefanič
  • Department of Vascular Surgery, East Slovak Institute of Cardiovascular Disease, Košice, Slovakia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Matan Katz
  • First Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Košice, Slovakia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Katarína Spišáková
  • First Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Košice, Slovakia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jozef Pella / Daniel Pella
  • First Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Košice, Slovakia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-05-23 | DOI: https://doi.org/10.1515/jbcpp-2016-0149

Abstract

Background:

Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects.

Methods:

In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Zennix fa Pleuran) and omega-3 PUFA 2.52 g+CoQ10 200 mg/day (Pharma Nord ApS) were added, res//. At the end of the 3-month period (±1 week), all patients were evaluated.

Results:

Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10.

Conclusions:

The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

Keywords: cardiovascular system diseases; coenzyme Q10; combined dyslipidemia; omega-3 fatty acids; statins

References

  • 1.

    Beignet C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Cholesterol Treatment Trialists’ (CTT) Collaborators (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366:1267–78.Google Scholar

  • 2.

    Shanes JG, Minadeo KN, Moret A, Groner M, Tabaie SA. Statin therapy in heart failure: prognostic effects and potential mechanisms. Am Heart J 2007;154:617–23.Web of ScienceGoogle Scholar

  • 3.

    Schuster H, Fox JC. Investigating cardiovascular risk reduction–the Rosuvastatin GALAXY Programme. Expert Opin Pharmacother 2004;5:1187–200.Google Scholar

  • 4.

    Chan DC, Watts GF. Dyslipidaemia in the metabolic syndrome and type 2 diabetes: pathogenesis, priorities, pharmacotherapies. Expert Opin Pharma-cother 2011;12:13–30.Google Scholar

  • 5.

    Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1997;3:213–19.Google Scholar

  • 6.

    Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 2007;115:450–8.Web of ScienceGoogle Scholar

  • 7.

    Schulte H, Cullen P, Assmann G. Obesity, mortality and cardiovascular disease in the Münster Heart Study (PROCAM). Atherosclerosis 1999;144:199–209.CrossrefGoogle Scholar

  • 8.

    Newman JW, Pedersen TL, Brandenburg VR, Harris WS, Shearer GC. Effect of omega-3 fatty acid ethyl esters on the oxylipin composition of lipoproteins in hypertriglyceridemic, statin-treated subjects. PLoS One 2014;9:e111471.Web of ScienceGoogle Scholar

  • 9.

    Foran JA, Carpenter DO, Hamilton MC, Knuth BA, Schwager SJ. Risk-based consumption advice for farmed Atlantic and wild Pacific salmon contaminated with dioxins and dioxin-like compounds, Environ. Health Perspect 2005;113:552–556.CrossrefGoogle Scholar

  • 10.

    Lim S, Barter P. Antioxidant effects of statins in the management of cardiometabolic disorders. J Atheroscler Thromb 2010;21:997–1010.CrossrefGoogle Scholar

  • 11.

    Cao J, Schwichtenberg KA, Hanson NQ, Tsai MY. Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clin Chem 2006;52:2265–72.CrossrefGoogle Scholar

  • 12.

    Rudkowska I, Caron-Dorval D, Verreault M, Couture P, Deshaies Y, Barbier O, et al. PPARalpha L162V polymorphism alters the potential of n-3 fatty acids to increase lipoprotein lipaseactivity. Mol Nutr Food Res 2010;54:543–50.CrossrefGoogle Scholar

  • 13.

    Marai I, Massalha S. Effect of omega-3 polyunsaturated fatty acids and vitamin D on cardiovascular diseases. Isr Med Assoc J 2014;16:117–21.Google Scholar

  • 14.

    Maresta A, Balduccelli M, Varani E, Marzilli M, Galli C, Heiman F, et al. Prevention of postcoronary angioplasty restenosis by omega-3 fatty acids: main results of the Esapent for Prevention of Restenosis Italian Study (ESPRIT). Am Heart J 2002;143:E5.Google Scholar

  • 15.

    Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997;65:1645–54.Google Scholar

  • 16.

    Littlefield N, Beckstrand RL, Luthy KE. Statins’ effect on plasma levels of Coenzyme Q10 and improvement in myopathy with supplementation. J Am Assoc Nurse Pract 2014;26:85–90.Web of ScienceGoogle Scholar

  • 17.

    Wyman M, Leonard M, Morledge T. Coenzyme Q10: a therapy for hypertension and statin–induced myalgia? Cleve Clin J Med 2010;77:435–42.CrossrefGoogle Scholar

  • 18.

    Fitzgerald JP. Comparative analysis of superoxide dismutase activities in a range of temperate and tropical teleost fish. Comp Biochem Physiol 1992;101:111–14.Google Scholar

  • 19.

    Macchia A, Romero M, D’Ettorre A, Tognoni G, Mariani J. Exploratory analysis on the use of statins with or without n-3 PUFA and major events in patients dis–charged for acute myocardial infarction: an observational retrospective study. PLoSOne 2013;8:e62772.Google Scholar

  • 20.

    Nambi V, Ballantyne CM. Combination therapy with statins and omega-3 fatty acids. Am J Cardiol 2006;98:34–8.CrossrefGoogle Scholar

  • 21.

    Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007;369:1090–8.Google Scholar

  • 22.

    Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, et al. COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators 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.Google Scholar

  • 23.

    Levy Y. Beyond cholesterol lowering: effect of statins on markers of cardiovascular disease. Isr Med Assoc J 2004;6:490–91.Google Scholar

  • 24.

    Schmelzer C, Niklowitz P, Okun JG, Haas D, Menke T, Döring F. Ubiquinol–induced gene expression signatures are translated into altered parameters of erythropoiesis and reduced low density lipoprotein cholesterol levels in humans. IUBMB Life 2011;64:42–8.CrossrefWeb of ScienceGoogle Scholar

  • 25.

    Mabuchi H, Nohara A, Kobayashi J, Kawashiri MA, Katsuda S, Inazu A, et al. Effects of CoQ10 supplementation on plasma lipoprotein lipid, CoQ10 and liver and muscle enzyme levels in hypercholesterolemic patients treated with atorvastatin: a randomized double-blind study. Atherosclerosis 2007;195:182–9.CrossrefGoogle Scholar

  • 26.

    Garrido-Maraver J, Cordero MD, Oropesa-Ávila M, Fernández Vega A, de la Mata M, Delgado Pavón A, et al. Coenzyme q10 therapy. Mol Syndromol 2014;5:187–97.CrossrefGoogle Scholar

  • 27.

    Fedacko J, Pella D, Fedackova P, Hänninen O, Tuomainen P, Jarcuska P, et al. Coenzyme Q(10) and selenium in statin-associated myopathy treatment. Can J Physiol Pharmacol 2013;91:165–70.Web of ScienceCrossrefGoogle Scholar

  • 28.

    Ansell BJ, Watson KE, Weiss RE, Fonarow GC. hsCRP and HDL effects of statins trial (CHEST): rapid effect of statin therapy on C-reactive protein and high-density lipoprotein levels A clinical investigation. Heart Dis 2003;5:2–7.CrossrefGoogle Scholar

  • 29.

    Du B, Xu G, Cao H, Cui W, Lin S, Liu Y, et al. Effects of atorvastatin on expression of ICAM-1 in atherosclerotic rabbits. J Cardiovasc Med 2013;14:120–26.Web of ScienceCrossrefGoogle Scholar

  • 30.

    Ylä-Herttuala S, Bentzon JF, Daemen M, Falk E, Garcia-Garcia HM, Herrmann J, et al. Stabilization of atherosclerotic plaques: an update. Eur Heart J 2013;34:3251–58.Web of ScienceCrossrefGoogle Scholar

  • 31.

    Ridker PM. Moving beyond JUPITER: will inhibiting inflammation reduce vascular event rates? Curr Atheroscler Rep 2013;15:295.Web of ScienceCrossrefGoogle Scholar

  • 32.

    Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes (PROVE IT – TIMI). N Engl J Med 2004;350:1495–504.Google Scholar

  • 33.

    Witting PK, Pettersson K, Letters J, Stocker R. Anti-atherogenic effect of coenzyme Q10 in apolipoprotein E gene knockout mice. Free Radic Biol Med 2000;29:295–305.Google Scholar

  • 34.

    Lee BJ, Huang YC, Chen SJ, Lin PT. Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with coronary artery disease. Nutrition 2012;28:250–55.CrossrefWeb of ScienceGoogle Scholar

  • 35.

    Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 2011;58:2047–67.Web of ScienceCrossrefGoogle Scholar

  • 36.

    Lee BJ, Huang YC, Chen SJ, Lin PT. Effects of co-enzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, and homocysteine) in patients with coronary artery disease. Nutrition 2012;28:767–72.CrossrefGoogle Scholar

  • 37.

    Kris-Etherton PM, Harris WS, Appel LJ, American Heart Association. Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002;106:2747–57.CrossrefGoogle Scholar

  • 38.

    Ohara Y, Peterson TE, Sayegh HS, Subramanian RR, Wilcox JN, Harrison DG. Dietary correction of hypercholesterolemia in the rabbit normalizes endothelial superoxide anion production. Circulation 1995;92:898–903.CrossrefGoogle Scholar

  • 39.

    Ledoux S, Laouari D, Essig M, Runembert I, Trugnan G, Michel JB, et al. Lovastatin enhances ecto-5′-nucleotidase activity and cell surface expression in endothelial cells: implication of Rho–family GTPases. Circ Res 2002;90:420–27.CrossrefGoogle Scholar

  • 40.

    Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, et al. Effect of intensive compared with moderate lipid-owering therapy on progression of coronary atherosclerosis: a randomized controlled trial. J Am Med Assoc 2004;9:1071–80.CrossrefGoogle Scholar

  • 41.

    Ridker PM. The JUPITER trial: results, controversies, and implications for prevention. Circ Cardiovasc Qual Outcomes 2009;2:279–85.Google Scholar

  • 42.

    Brooks JD, Musiek ES, Koestner TR, Stankowski JN, Howard JR, Brunoldi EM, et al. The fatty acid oxidation product 15-A3t-isoprostane is a potent inhibitor of NFκB transcription and macrophage transformation. J Neurochem 2011;119:604–16.CrossrefWeb of ScienceGoogle Scholar

  • 43.

    Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, et al.: European guidelines on cardiovascular disease prevention in clinical practise: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practise. Eur Heart J 2007;28:2375–414.CrossrefGoogle Scholar

  • 44.

    Hamilton SJ, Chew GT, Watts GF. Coenzyme Q10 improves endothelial dysfunction in statin-treated type 2 diabetic patients. Diabetes Care 2009;32:810–12.CrossrefWeb of ScienceGoogle Scholar

About the article

Corresponding author: Štefan Tóth, MD, MBA, PhD, First Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 041 90 Košice, Slovakia, Phone: +421 904 518 038


Received: 2016-10-01

Accepted: 2017-03-24

Published Online: 2017-05-23

Published in Print: 2017-07-26


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: This study was entirely funded by PROBIO ITMS No.26220220104.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 28, Issue 4, Pages 327–336, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2016-0149.

Export Citation

©2017 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Juan M. Suárez-Rivero, Carmen J. Pastor-Maldonado, Mario de la Mata, Marina Villanueva-Paz, Suleva Povea-Cabello, Mónica Álvarez-Córdoba, Irene Villalón-García, Alejandra Suárez-Carrillo, Marta Talaverón-Rey, Manuel Munuera, and José A. Sánchez-Alcázar
International Journal of Molecular Sciences, 2019, Volume 20, Number 20, Page 5195
[2]
Hua Qu, Ming Guo, Hua Chai, Wen‐ting Wang, Zhu‐ye Gao, and Da‐zhuo Shi
Journal of the American Heart Association, 2018, Volume 7, Number 19
[3]

Comments (0)

Please log in or register to comment.
Log in