CoQ10 Function and Role in Heart Failure and Ischemic Heart Disease

Annual Review of Nutrition

Volumn 35, Issue 1, 2015, Pages 175-213

  Ayer, Anita ^a   Macdonald, Peter ^b   Stocker, Roland ^a,c  

^a Vascular Biology   (Australia)

^b VICTOR CHANG CARDIAC RESEARCH INSTITUTE   (Australia)

^c UNIVERSITY OF NEW SOUTH WALES   (Australia)

Author keywords

Cardiovascular disease; Subcellular distribution; Therapy; Ubiquinol; Ubiquinone

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTIOXIDANT; ENDOTHELIAL NITRIC OXIDE SYNTHASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; REACTIVE OXYGEN METABOLITE; UBIDECARENONE; UBIQUINONE;

ACUTE CORONARY SYNDROME; ANTIOXIDANT ACTIVITY; BIOAVAILABILITY; BIOLOGICAL FUNCTIONS; BIOSYNTHESIS; CARDIOMYOPATHY; CARDIOPULMONARY BYPASS; CATABOLISM; CELLULAR DISTRIBUTION; DIET SUPPLEMENTATION; ENERGY YIELD; ENZYME DEFICIENCY; GOLGI COMPLEX; HEART FAILURE; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART OUTPUT; HEART SURGERY; HUMAN; HYPERTENSION; INOTROPISM; ISCHEMIC HEART DISEASE; LIVER MICROSOME; LYSOSOME; MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL PERMEABILITY; MYOPATHY; NONHUMAN; OXIDATION REDUCTION STATE; PATHOGENESIS; PEROXISOME; PRIMARY UBIDECARENONE DEFICIENCY; PRIORITY JOURNAL; PROTON TRANSPORT; REVIEW; SECONDARY UBIDECARENONE DEFICIENCY; TISSUE DISTRIBUTION; AGE; ANALOGS AND DERIVATIVES; ANIMAL; CHEMICALLY INDUCED; DEFICIENCY; DIET; DIETARY SUPPLEMENT; MUSCULAR DISEASES; MYOCARDIAL ISCHEMIA; PHYSIOLOGY; SKELETAL MUSCLE;

ANIMALIA;

AGE FACTORS; ANIMALS; ANTIOXIDANTS; DIET; DIETARY SUPPLEMENTS; HEART FAILURE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MUSCLE, SKELETAL; MUSCULAR DISEASES; MYOCARDIAL ISCHEMIA; TISSUE DISTRIBUTION; UBIQUINONE;

EID: 84937572996     PISSN: 01999885     EISSN: 15454312     Source Type: Book Series    
DOI: 10.1146/annurev-nutr-071714-034258     Document Type: Review

References (198)

1. Åberg F, Appelkvist E-L, Dallner G, Ernster L. 1992. Distribution and redox state of ubiquinones in rat and human tissues. Arch. Biochem. Biophys. 295:230-34
2. Alam SS, Nambudiri AM, Rudney H. 1975. J-Hydroxybenzoate: polyprenyl transferase and the prenylation of 4-aminobenzoate in mammalian tissues. Arch. Biochem. Biophys. 171:183-90
3. Allan CM, Awad AM, Johnson JS, Shirasaki DI, Wang C, et al. 2010. Identification ofCoq11, a new coenzymeQbiosynthetic protein in theCoQ-synthome in Saccharomyces cerevisiae. J. Biol. Chem. 290:7517-34
4. Ashraf S,Gee HY,Woerner S, Xie LX, Vega-Warner V, et al. 2013. ADCK4 mutations promote steroidresistant nephrotic syndrome through CoQ10 biosynthesis disruption. J. Clin. Investig. 123:5179-89
5. Banach M, Serban C, Sahebkar A, Ursoniu S, Rysz J, et al. 2015. Effects of coenzyme Q10 on statininduced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin. Proc. 90:24-34
6. Barry E, Alvarez JA, Scully RE, Miller TL, Lipshultz SE. 2007. Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management. Expert Opin. Pharmacother. 8:1039-58
7. Barshop BA, Gangoiti JA. 2007. Analysis of coenzyme Q in human blood and tissues. Mitochondrion 7(Suppl.):S89-93
8. Battino M, Gorini A, Villa RF, GenovaML, Bovina C, et al. 1995. Coenzyme Q content in synaptic and non-synaptic mitochondria from different brain regions in the ageing rat. Mech. Ageing Dev. 78:173-87
9. Beal MF, Oakes D, Shoulson I, Henchcliffe C, GalpernWR, et al. 2014. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 71:543-52
10. Bech O, Sørensen J, Jensen M, Diamant B, Steiness E. 1990. Effects of long-term coenzymeQ10 and captopril treatment on survival and functional capacity in rats with experimentally induced heart infarction. J. Pharmacol. Exp. Ther. 255:346-50
11. Belardinelli R, Muçaj A, Lacalaprice F, Solenghi M, Principi F, et al. 2005. Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failure. Biofactors 25:137-45
12. Belardinelli R, Tiano L, Littarru GP. 2008. Oxidative stress, endothelial function and coenzyme Q10. Biofactors 32:129-33
13. Bentinger M, Dallner G, Chojnacki T, Swiezewska E. 2003. Distribution and breakdown of labeled coenzyme Q10 in rat. Free Radic. Biol. Med. 34:563-75
14. Bentinger M, Tekle M, Dallner G, Brismar K, Gustafsson JA, et al. 2012. Influence of liver-X-receptor on tissue cholesterol, coenzyme Q and dolichol content. Mol. Membr. Biol. 29:299-308
15. Berman M, Erman A, Ben-Gal T, Dvir D, Georghiou GP, et al. 2004. Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study. Clin. Cardiol. 27:295-99
16. Bertazzoli C, Sala L, Ballerini L, Watanabe T, Folkers K. 1976. Effect of adriamycin on the activity of the succinate dehydrogenase-coenzyme Q10 reductase of the rabbit myocardium. Res. Commun. Chem. Pathol. Pharmacol. 15:797-800
17. Beyer RE, Burnett BA, Cartwright KJ, Edington DW, Falzon MJ, et al. 1985. Tissue coenzyme Q (ubiquinone) and protein concentrations over the life span of the laboratory rat. Mech. Ageing Dev. 32:267-81
18. Bhagavan HN, Chopra RK. 2006. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic. Res. 40:445-53
19. Bhagavan HN, Chopra RK, Craft NE, Chitchumroonchokchai C, Failla ML. 2007. Assessment of coenzyme Q10 absorption using an in vitro digestion-Caco-2 cell model. Int. J. Pharm. 333:112-17
20. Bogsrud MP, Langslet G, Ose L, Arnesen KE, Sm Stuen MC, et al. 2013. No effect of combined coenzyme Q10 and selenium supplementation on atorvastatin-induced myopathy. Scand. Cardiovasc. J. 47:80-87
21. Bookstaver DA, Burkhalter NA, Hatzigeorgiou C. 2012. Effect of coenzyme Q10 supplementation on statin-induced myalgias. Am. J. Cardiol. 110:526-29
22. Bowry VW, Ingold KU, Stocker R. 1992. Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant. Biochem. J. 288:341-44
23. Braunwald E. 2008. Biomarkers in heart failure. N. Engl. J. Med. 358:2148-59
24. Bui AL, Horwich TB, Fonarow GC. 2011. Epidemiology and risk profile of heart failure. Nat. Rev. Cardiol. 8:30-41
25. Caso G, Kelly P, McNurlan MA, LawsonWE. 2007. Effect of coenzyme Q10 on myopathic symptoms in patients treated with statins. Am. J. Cardiol. 99:1409-12
26. Chai W, Novotny R, Maskarinec G, Marchand LL, Franke AA, Cooney RV. 2014. Serum coenzyme Q10, α-tocopherol, γ-tocopherol, and C-reactive protein levels and body mass index in adolescent and premenopausal females. J. Am. Coll. Nutr. 33:192-97
27. Chello M, Mastroroberto P, Romano R, Bevacqua E, Pantaleo D, et al. 1994. Protection by coenzyme Q10 from myocardial reperfusion injury during coronary artery bypass grafting. Ann. Thorac. Surg. 58:1427-32
28. Chen YF, Lin YT, Wu SC. 1994. Effectiveness of coenzyme Q10 on myocardial preservation during hypothermic cardioplegic arrest. J. Thorac. Cardiovasc. Surg. 107:242-47
29. Choe JY, Combs AB, Folkers K. 1979. Prevention by coenzymeQ10 of the electrocardiographic changes induced by adriamycin in rats. Res. Commun. Chem. Pathol. Pharmacol. 23:199-202
30. Choe JY, Combs AB, Saji S, Folkers K. 1979. Study of the combined and separate administration of doxorubicin and coenzyme Q10 on mouse cardiac enzymes. Res. Commun. Chem. Pathol. Pharmacol. 24:595-98
31. Chopra RK, Goldman R, Sinatra ST, Bhagavan HN. 1997. Relative bioavailability of coenzyme Q10 formulations in human subjects. Int. J. Vitam. Nutr. Res. 68:109-13
32. Conklin KA. 2005. CoenzymeQ10 for prevention of anthracycline-induced cardiotoxicity. Integr. Cancer Ther. 4:110-30
33. Cortes EP, Gupta M, Chou C, Amin VC, Folkers K. 1978. Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treat. Rep. 62:887-91
34. Cowie MR, Wood DA, Coats AJ, Thompson SG, Suresh V, et al. 2000. Survival of patients with a new diagnosis of heart failure: a population based study. Heart 83:505-10
35. Crane F, Hatefi Y, Lester R, Widmer C. 1957. Isolation of a quinone from beef heart mitochondria. Biochim. Biophys. Acta 25:220-21
36. Crane F, Sun I, Clark M, Grebing C, Low H. 1985. Transplasma-membrane redox systems in growth and development. Biochim. Biophys. Acta 811:233-64
37. Crestanello JA, Doliba NM, Doliba NM, Babsky AM, Niborii K, et al. 2002. Effect of coenzyme Q10 supplementation on mitochondrial function aftermyocardial ischemia reperfusion. J. Surg. Res. 102:221-28
38. Crestanello JA, Kamelgard J, Lingle DM, Mortensen SA, Rhode M, Whitman GJ. 1996. Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance to ischemia by coenzyme Q10 pretreatment. J. Thorac. Cardiovasc. Surg. 111:443-50
39. Dadabayev AR, YinG,Latchoumycandane C, McIntyreTM, LesnefskyEJ, Penn MS. 2014. Apolipoprotein A1 regulates coenzymeQ10 absorption andmitochondrial function and infarct size in amousemodel of myocardial infarction. J. Nutr. 144:1030-36
40. Dallner G, Stocker R. 2010. Coenzyme Q10. In Encyclopedia of Dietary Supplements, ed. P Coates, JM Betz, MR Blackman, G Craff, MM Levine, et al., pp. 157-65. New York: Informa Healthc
41. De Cabo R, Cabello R, Rios M, Lopez-Lluch G, Ingram DK, et al. 2004. Calorie restriction attenuates age-related alterations in the plasma membrane antioxidant system in rat liver. Exp. Gerontol. 39:297-304
42. Deichmann RE, Lavie CJ, Dornelles AC. 2012. Impact of coenzyme Q-10 on parameters of cardiorespiratory fitness and muscle performance in older athletes taking statins. Phys. Sportsmed. 40:88-95
43. Devun F,Walter L, Belliere J, Cottet-Rousselle C, Leverve X, Fontaine E. 2010. Ubiquinone analogs: a mitochondrial permeability transition pore-dependent pathway to selective cell death. PLOS ONE 5:e11792
44. DoimoM, Desbats MA, Cerqua C, Cassina M, Trevisson E, Salviati L. 2014. Genetics of coenzymeQ10 deficiency. Mol. Syndromol. 5:156-62
45. Domae N, Sawada H, Matsuyama E, Konishi T, Uchino H. 1981. Cardiomyopathy and other chronic toxic effects induced in rabbits by doxorubicin and possible prevention by coenzyme Q10. Cancer Treat. Rep. 65:79-91
46. Emmanuele V, Lopez LC, Berardo A, Naini A, Tadesse S, et al. 2012. Heterogeneity of coenzyme Q10 deficiency: patient study and literature review. Arch. Neurol. 69:978-83
47. Failla ML, Chitchumroonchokchai C, Aoki F. 2014. Increased bioavailability of ubiquinol compared to that of ubiquinone is due to more efficient micellarization during digestion and greater GSH-dependent uptake and basolateral secretion by Caco-2 cells. J. Agric. Food Chem. 62:7174-82
48. Fatkin D, Csanz Cardiac Genetic Diseases Council Writing Group members. 2011. Guidelines for the diagnosis and management of familial dilated cardiomyopathy. Heart Lung Circ. 20:691-93
49. Fedacko J, Pella D, Fedackova P, Hanninen O, Tuomainen P, et al. 2013. Coenzyme Q10 and selenium in statin-associated myopathy treatment. Can. J. Physiol. Pharmacol. 91:165-70
50. Fernandez-Ayala DJ, Brea-CalvoG, López-LluchG,Navas P. 2005. CoenzymeQdistribution inHL-60 human cells depends on the endomembrane system. Biochim. Biophys. Acta 1713:129-37
51. Ferrante K, Shefner J, Zhang H, Betensky R, O Brien M, et al. 2005. Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS. Neurology 65:1834-36
52. Flowers N, Hartley L, Todkill D, Stranges S, Rees K. 2014. Co-enzyme Q10 supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst. Rev. 12:CD010405
53. FolkersK, Baker L, Richardson PC. 1980. Biomedical and clinical research on coenzymeQ10. In Biomedical and Clinical Aspects of Coenzyme Q, ed. K Folkers, Y Yamamura, Y Ito, 2:447-54. Amsterdam: Elsevier
54. FolkersK,Choe JY, Combs AB. 1978. Rescue by coenzymeQ10 from electrocardiographic abnormalities caused by the toxicity of adriamycin in the rat. PNAS 75:5178-80
55. Folkers K, Langsjoen P, Willis R, Richardson P, Xia L-J, et al. 1990. Lovastatin decreases coenzyme Q levels in humans. PNAS 87:8931-34
56. Folkers K, Littarru G, Ho L, Runge TM, Havanonda S, Cooley D. 1970. Evidence for a deficiency of coenzyme Q10 in human heart disease. Int. Z. Vitaminforsch. 40:380-90
57. Folkers K, Liu M, Watanabe T, Porter TH. 1977. Inhibition by adriamycin of themitochondrial biosynthesis of coenzyme Q10 and implication for the cardiotoxicity of adriamycin in cancer patients. Biochem. Biophys. Res. Commun. 77:1536-42
58. Folkers K,Wolaniuk J, Simonsen R, Morishita M, Vadhanavikit S. 1985. Biochemical rationale and the cardiac response of patients with muscle disease to therapy with coenzyme Q10. PNAS 82:4513-16
59. Fotino AD, Thompson-Paul AM, Bazzano LA. 2013. Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis. Am. J. Clin. Nutr. 97:268-75
60. Garjani A, Andalib S, Biabani S, Soraya H, Doustar Y, et al. 2011. Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat. Eur. J. Pharmacol. 666:135-41
61. Garrido-Maraver J, Cordero MD, Oropesa-A vila M, Fernandez Vega A, de la Mata M, et al. 2014. Coenzyme Q10 therapy. Mol. Syndromol. 5:187-97
62. Gay CA, Stocker R. 2004. Simultaneous determination of coenzyme Q10, cholesterol, and major cholesterylesters in human blood plasma. Methods Enzymol. 378:162-69
63. Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, et al. 1993. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J. Clin. Pharmacol. 33:226-29
64. Gómez-Diaz C, Villalba J, Perez-VicenteR,Crane F, Navas P. 1997. Ascorbate stabilization is stimulated in HL-60 cells by CoQ10 increase at the plasma membrane. Biochem. Biophys. Res. Commun. 234:79-81
65. Gonzalez-Mariscal I, Garcia-Teston E, Padilla S, Martin-Montalvo A, Pomares-Viciana T, et al. 2014. Regulation of coenzyme Q biosynthesis in yeast: a new complex in the block. IUBMB Life 66:63-70
66. Grunler J, Parmryd I. 1999. Subcellular distribution of farnesyl protein transferase in rat liver. FEBS Lett. 455:233-37
67. Haas RH. 2007. The evidence basis for coenzyme Q therapy in oxidative phosphorylation disease. Mitochondrion 7(Suppl.):S136-45
68. Hano O, Thompson-Gorman SL, Zweier JL, Lakatta EG. 1994. Coenzyme Q10 enhances cardiac functional and metabolic recovery and reduces Ca2+ overload during postischemic reperfusion. Am. J. Physiol. 266:H2174-81
69. Harker-Murray AK, Tajik AJ, Ishikura F, Meyer D, Burnett JC, Redfield MM. 2000. The role of coenzyme Q10 in the pathophysiology and therapy of experimental congestive heart failure in the dog. J. Card. Fail. 6:233-42
70. He CH, Xie LX, Allan CM, Tran UC, Clarke CF. 2014. Coenzyme Q supplementation or overexpression of the yeast Coq8 putative kinase stabilizes multi-subunit Coq polypeptide complexes in yeast coq null mutants. Biochim. Biophys. Acta 1841:630-44
71. Ho MJ, Bellusci A, Wright JM. 2009. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension. Cochrane Database Syst. Rev. 4:CD007435
72. Hofman-BangC,Rehnqvist N, Swedberg K, Wiklund I,Åstr omH. 1995. CoenzymeQ10 as an adjunctive in the treatment of chronic congestive heart failure. J. Card. Fail. 1:101-7
73. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, et al. 2005. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 112:e154-235
74. Iarussi D, Auricchio U, Agretto A, Murano A, Giuliano M, et al. 1994. Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Mol. Aspects Med. 15(Suppl.):s207-12
75. Ivanov AV, Gorodetskaya EA, Kalenikova EI, Medvedev OS. 2013. Single intravenous injection of coenzyme Q10 protects the myocardium after irreversible ischemia. Bull. Exp. Biol. Med. 155:771-74
76. Jeya M, Moon HJ, Lee JL, Kim IW, Lee JK. 2010. Current state of coenzyme Q10 production and its applications. Appl. Microbiol. Biotechnol. 85:1653-63
77. Jin G, Kubo H, Kashiba M, Horinouchi R, Hasegawa M, et al. 2008. Saposin B is a human coenzyme Q10-binding/transfer protein. J. Clin. Biochem. Nutr. 42:167-74
78. Judy WV, Stogsdill WW, Folkers K. 1993. Myocardial preservation by therapy with coenzyme Q10 during heart surgery. Clin. Investig. 71:S155-61
79. Kalen A, Appelkvist EL, Dallner G. 1989. Age-related changes in the lipid compositions of rat and human tissues. Lipids 24:579-84
80. Kalen A, Appelkvist EL, Chojnacki T, Dallner G. 1990. Nonaprenyl-4-hydroxybenzoate transferase, an enzyme involved in ubiquinone biosynthesis, in the endoplasmic reticulum-Golgi system of rat liver. J. Biol. Chem. 265:1158-64
81. KameiM, FujitaT,Kanbe T, Sasaki K, OshibaK, et al. 1985. The distribution and content of ubiquinone in foods. Int. J. Vitam. Nutr. Res. 56:57-63
82. Kanji S, Seely D, Yazdi F, Tetzlaff J, Singh K, et al. 2012. Interactions of commonly used dietary supplements with cardiovascular drugs: a systematic review. Syst. Rev. 1:26-42
83. Katayama K, Fujita T. 1972. Studies on lymphatic absorption of 1-,2-(3 H)-coenzyme Q 10 in rats. Chem. Pharm. Bull. (Tokyo) 20:2585-92
84. Keogh A, Fenton S, Leslie C, Aboyoun C, Macdonald P, et al. 2003. Randomised double-blind, placebocontrolled trial of coenzyme Q10 therapy in class II and III systolic heart failure. Heart Lung Circ. 12:135-41
85. Khatta M, Alexander BS, KrichtenCM, Fisher ML, FreudenbergerR, et al. 2000. The effect of coenzyme Q10 in patients with congestive heart failure. Ann. Intern. Med. 132:636-40
86. Khorrami A, GarjaniA,Ghanbarzadeh S, Andalib S. 2014. Reduction of coenzymeQ10 content: a possible effect of isoproterenol on heart failure and myocardial infarction in rat. Drug Res. (Stuttg.) 64:177-81
87. Kocharian A, Shabanian R, Rafiei-Khorgami M, Kiani A, Heidari-Bateni G. 2009. Coenzyme Q10 improves diastolic function in children with idiopathic dilated cardiomyopathy. Cardiol. Young 19:501-6
88. KonishiT,Nakamura Y,Konishi T, KawaiC. 1985. Improvement in recovery of left ventricular function during reperfusion with coenzyme Q10 in isolated working rat heart. Cardiovasc. Res. 19:38-43
89. Krisans SK. 1996. Cell compartmentalization of cholesterol biosynthesis. Ann. N. Y. Acad. Sci. 804:142-64
90. Krum H, Jelinek MV, Stewart S, Sindone A, Atherton JJ, et al. 2006. Guidelines for the prevention, detection and management of people with chronic heart failure in Australia 2006. Med. J. Aust. 185:549-57
91. Kuklinski B,Weissenbacher E, Fahnrich A. 1994. Coenzyme Q10 and antioxidants in acute myocardial infarction. Mol. Aspects Med. 15(Suppl.):s143-47
92. Langsjoen PH, Langsjoen PH, Folkers K. 1993. Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment. Clin. Investig. 71:S140-44
93. Langsjoen PH, Vadhanavikit S, Folkers K. 1985. Effective treatment with coenzyme Q10 of patients with chronic myocardial disease. Drugs Exp. Clin. Res. 11:577-79
94. Langsjoen PH, Vadhanavikit S, Folkers K. 1985. Response of patients in classes III and IV of cardiomyopathy to therapy in a blind and crossover trial with coenzyme Q10. PNAS 82:4240-44
95. Lass A, Kwong L, Sohal RS. 1999. Mitochondrial coenzyme Q content and aging. Biofactors 9:199-205
96. Lee BJ, Huang YC, Chen SJ, Lin PT. 2012. Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with coronary artery disease. Nutrition 28:250-55
97. Lee BJ, Tseng YF, Yen CH, Lin PT. 2013. Effects of coenzyme Q10 supplementation (300 mg/day) on antioxidation and anti-inflammation in coronary artery disease patients during statins therapy: a randomized, placebo-controlled trial. Nutr. J. 12:142
98. Legha SS, Wang YM, Mackay B, Ewer M, Hortobagyi GN, et al. 1982. Clinical and pharmacologic investigation of the effects of α-tocopherol on adriamycin cardiotoxicity. Ann. N. Y. Acad. Sci. 393:411-18
99. Levy HB, Kohlhaas HK. 2006. Considerations for supplementing with coenzyme Q10 during statin therapy. Ann. Pharmacother. 40:290-94
100. Lipinski MJ,Cauthen CA,Biondi-ZoccaiGG,Abbate A, Vrtovec B, et al. 2009. Meta-analysis of randomized controlled trials of statins versus placebo in patients with heart failure. Am. J. Cardiol. 104:1708-16
101. Liu G, Zheng XX, Xu YL, Lu J, Hui RT, Huang XH. 2014. Effects of lipophilic statins for heart failure: a meta-analysis of 13 randomised controlled trials. Heart Lung Circ. 23:970-77
102. Lonnrot K, Tolvanen JP, Porsti I, Ahola T, Hervonen A, Alho H. 1999. CoenzymeQ10 supplementation and recovery from ischemia in senescent rat myocardium. Life Sci. 64:315-23
103. López LC, Schuelke M, Quinzii CM, Kanki T, Rodenburg RJ, et al. 2006. Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations. Am. J. Hum. Genet. 79:1125-29
104. Macdonald PS. 2010. Heart failure with preserved ejection fraction-coming to terms with an oxymoron. Med. J. Aust. 192:4-5
105. Madmani ME, Yusuf Solaiman A, Tamr Agha K, Madmani Y, Shahrour Y, et al. 2014. Coenzyme Q10 for heart failure. Cochrane Database Syst. Rev. 6:CD008684
106. Makhija N, Sendasgupta C, Kiran U, Lakshmy R, HoteMP, et al. 2008. The role of oral coenzyme Q10 in patients undergoing coronary artery bypass graft surgery. J. Cardiothorac. Vasc. Anesth. 22:832-39
107. Marbois B, Xie LX, Choi S, Hirano K, Hyman K, Clarke CF. 2010. para-Aminobenzoic acid is a precursor in coenzyme Q6 biosynthesis in Saccharomyces cerevisiae. J. Biol. Chem. 285:27827-38
108. Marcoff L, Thompson PD. 2007. The role of coenzyme Q10 in statin-associated myopathy: a systematic review. J. Am. Coll. Cardiol. 49:2231-37
109. McMurray JJ, DunselmanP,Wedel H, Cleland JG, LindbergM,et al. 2010. CoenzymeQ10, rosuvastatin, and clinical outcomes in heart failure: a pre-specified substudy of CORONA (Controlled Rosuvastatin Multinational Study in Heart Failure). J. Am. Coll. Cardiol. 56:1196-204
110. McMurray JJ, Packer M, Desai AS, Gong J, LefkowitzMP, et al. 2014. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N. Engl. J. Med. 371:993-1004
111. Miles MV. 2007. The uptake and distribution of coenzyme Q10. Mitochondrion 7(Suppl.):S72-77
112. Mills E, Wu P, Johnston BC, Gallicano K, Clarke M, Guyatt G. 2005. Natural health product-drug interactions: a systematic review of clinical trials. Ther. Drug Monit. 27:549-57
113. Mischley LK, Allen J, Bradley R. 2012. Coenzyme Q10 deficiency in patients with Parkinson s disease. J. Neurol. Sci. 318:72-75
114. Mitchell P. 1975. Protonmotive redox mechanism of the cytochrome bc1 complex in the respiratory chain: protonmotive ubiquinone cycle. FEBS Lett. 56:1-6
115. Mohr D, Umeda Y, Redgrave TG, Stocker R. 1999. Antioxidant defenses in rat intestine and mesenteric lymph. Redox Rep. 4:79-87
116. Molyneux SL, Young JM, Florkowski CM, Lever M, George PM. 2008. Coenzyme Q10: Is there a clinical role and a case for measurement? Clin. Biochem. Rev. 29:71-82
117. Moreno-Fernandez AM, CorderoMD, Garrido-Maraver J, Alcocer-G omez E, Casas-Barquero N, et al. 2012. Oral treatmentwith amitriptyline induces coenzymeQdeficiency and oxidative stress in psychiatric patients. J. Psychiatr. Res. 46:341-45
118. Morisco C,Nappi A, Argenziano L, Sarno D, Fonatana D, et al. 1994. Noninvasive evaluation of cardiac hemodynamics during exercise in patients with chronic heart failure: effects of short-term coenzymeQ10 treatment. Mol. Aspects Med. 15(Suppl.):s155-63
119. MoriscoC,Trimarco B,Condorelli M. 1993. Effect of coenzymeQ10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Clin. Investig. 71:S134-36
120. Morita K, Ihnken K, Buckberg GD, Young HH. 1995. Studies of hypoxemic/reoxygenation injury: without aortic clamping. VII. Counteraction of oxidant damage by exogenous antioxidants: coenzyme Q10. J. Thorac. Cardiovasc. Surg. 110:1221-27
121. Mortensen SA, Rosenfeldt F, KumarA,Dolliner P, Filipiak KJ, et al. 2014. The effect of coenzymeQ10 on morbidity and mortality in chronic heart failure. Results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2:641-49
122. Mortensen SA, Vadhanavikit S, Baandrup U, Folkers K. 1985. Long-term coenzyme Q10 therapy: a major advance in the management of resistant myocardial failure. Drugs Exp. Clin. Res. 11:581-93
123. Mugoni V, Postel R, Catanzaro V, De Luca E, Turco E, et al. 2013. Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis. Cell 152:504-18
124. Munkholm H, Hansen HH, Rasmussen K. 1999. Coenzyme Q10 treatment in serious heart failure. Biofactors 9:285-89
125. Murphy CJ,Oudit GY. 2010. Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment. J. Card. Fail. 16:888-900
126. Muthukumaran K, Leahy S, Harrison K, Sikorska M, Sandhu JK, et al. 2014. Orally delivered water soluble coenzyme Q10 (Ubisol-Q10) blocks on-going neurodegeneration in rats exposed to paraquat: potential for therapeutic application in Parkinson s disease. BMC Neurosci. 15:21-32
127. Nagai S, Miyazaki Y, Ogawa K, Satake T, Sugiyama S, Ozawa T. 1985. The effect of coenzyme Q10 on reperfusion injury in canine myocardium. J. Mol. Cell. Cardiol. 17:873-84
128. Nakamura T, Ohno T, Hamamura K, Sato T. 1999. Metabolism of coenzyme Q10: biliary and urinary excretion study in Guinea pigs. Biofactors 9:111-19
129. Natl. Inst. Health. 2014. Coenzyme Q10 (CoQ10): What You Need to Know. Bethesda, MD: Natl. Cent. Complement. Integr. Health. http://nccam.nih.gov/health/supplements/coq10
130. Nordman T, Xia L, Bj orkhem-Bergman L, Damdimopoulos A, Nalvarte I, et al. 2003. Regeneration of the antioxidant ubiquinol by lipoamide dehydrogenase, thioredoxin reductase and glutathione reductase. Biofactors 18:45-50
131. Ogasahara S,Engel AG, FrensD,Mack D. 1989. Muscle coenzymeQdeficiency in familial mitochondrial encephalomyopathy. PNAS 86:2379-82
132. Ohhara H, Kanaide H, Yoshimura R, Okada M, Nakamura M. 1981. A protective effect of coenzyme Q10 on ischemia and reperfusion of the isolated perfused rat heart. J. Mol. Cell. Cardiol. 13:65-74
133. Okuma K, Ota K. 1986. The effect of coenzyme Q10 on ECG changes induced by doxorubicin (Adriamycin). In Biomedical and Clinical Aspects of Coenzyme Q, ed. K Folkers, Y Yamamura, 5:247-56. Amsterdam: Elsevier
134. Papucci L, SchiavoneN,Witort E,Donnini M, Lapucci A, et al. 2003. CoenzymeQ10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property. J. Biol. Chem. 278:28220-28
135. Paulus WJ, Tschope C. 2013. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J. Am. Coll. Cardiol. 62:263-71
136. Permanetter B, R ossy W, Klein G, Weingartner F, Seidl K, Blomer H. 1992. Ubiquinone (coenzyme Q10) in the long-term treatment of idiopathic dilated cardiomyopathy. Eur. Heart J. 13:1528-33
137. Pierrel F, Hamelin O, Douki T, Kieffer-Jaquinod S, Muhlenhoff U, et al. 2010. Involvement of mitochondrial ferredoxin and para-aminobenzoic acid in yeast coenzyme Q biosynthesis. Chem. Biol. 17:449-59
138. Poggesi L, Galanti G, Comeglio M, Toncelli L, Vinci M. 1991. Effect of coenzymeQ10 on left ventricular function in patients with dilative cardiomyopathy: amedium-term randomized double-blind study versus placebo. Curr. Ther. Res. 49:878-86
139. Popov VN, Purvis AC, Skulachev VP, Wagner AM. 2001. Stress-induced changes in ubiquinone concentration and alternative oxidase in plant mitochondria. Biosci. Rep. 21:369-79
140. Pourmoghaddas M, Rabbani M, Shahabi J, Garakyaraghi M, Khanjani R, Hedayat P. 2014. Combination of atorvastatin/coenzyme Q10 as adjunctive treatment in congestive heart failure: a double-blind randomized placebo-controlled clinical trial. ARYA Atheroscler. 10:1-5
141. Pravst I, Žmitek K, Žmitek J. 2010. Coenzyme Q10 contents in foods and fortification strategies. Crit. Rev. Food Sci. Nutr. 50:269-80
142. Quinzii CM, HiranoM. 2011. Primary and secondary CoQ10 deficiencies in humans. Biofactors 37:361-65
143. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. 2003. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 289:194-202
144. Rengo F, Abete P, Landino P, Leosco D, Covelluzzi F, et al. 1993. Role of metabolic therapy in cardiovascular disease. Clin. Investig. 71:S124-28
145. Ronca-Testoni S, Zucchi R, Ronca F, Bertelli A. 1992. Effect of carnitine and coenzyme Q10 on the calcium uptake in heart sarcoplasmic reticulum of rats treated with anthracyclines. Drugs Exp. Clin. Res. 18:437-42
146. Rosenfeldt F, Hilton D, Pepe S, Krum H. 2003. Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure. Biofactors 18:91-100
147. Rosenfeldt F, Marasco S, Lyon W, Wowk M, Sheeran F, et al. 2005. Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility ofmyocardial tissue. J. Thorac. Cardiovasc. Surg. 129:25-32
148. Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, et al. 2007. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J. Hum. Hypertens. 21:297-306
149. Rosenfeldt FL, Pepe S, Ou R, Mariani JA, Rowland MA, et al. 1999. Coenzyme Q10 improves the tolerance of the senescent myocardium to aerobic and ischemic stress: studies in rats and in human atrial tissue. Biofactors 9:291-99
150. Rossi E, Lombardo A, Testa M, Lippa S, Oradei A, et al. 1991. CoenzymeQ10 in ischaemic cardiopathy. In Biomedical and Clinical Aspects of Coenzyme Q, ed. K Folkers, Y Yamamura, GP Littarru, pp. 321-26. Amsterdam: Elsevier
151. R otig A, Appelkvist E-L, Geromel V, Chretien D, KadhomN, et al. 2000. Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency. Lancet 356:391-95
152. Saito Y, Fukuhara A, Nishio K, Hayakawa M, Ogawa Y, et al. 2009. Characterization of cellular uptake and distribution of coenzyme Q10 and vitamin E in PC12 cells. J. Nutr. Biochem. 20:350-57
153. SanbeA,TanonakaK,NiwanoY,Takeo S. 1994. Improvement of cardiac function andmyocardial energy metabolism of rats with chronic heart failure by long-term coenzyme Q10 treatment. J. Pharmacol. Exp. Ther. 269:51-56
154. SanoobarM, Eghtesadi S, Azimi A,Khalili M, Khodadadi B, et al. 2015. CoenzymeQ10 supplementation ameliorates inflammatory markers in patients with multiple sclerosis: a double blind, placebo, controlled randomized clinical trial. Nutr. Neurosci. 18:169-76
155. Sevin DC, Sauer U. 2014. Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli. Nat. Chem. Biol. 10:266-72
156. Shults CW, Flint Beal M, Song D, Fontaine D. 2004. Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson s disease. Exp. Neurol. 188:491-94
157. Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, et al. 2002. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch. Neurol. 59:1541-50
158. Sikorska M, Lanthier P, Miller H, Beyers M, Sodja C, et al. 2014. Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson s disease. Neurobiol. Aging 35:2329-46
159. Silver MA, Langsjoen PH, Szabo S, Patil H, Zelinger A. 2004. Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction. Am. J. Cardiol. 94:1306-10
160. Singh RB, Neki NS, Kartikey K, Pella D, Kumar A, et al. 2003. Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction. Mol. Cell. Biochem. 246:75-82
161. Singh RB, Wander GS, Rastogi A, Shukla PK, Mittal A, et al. 1998. Randomized, double-blind placebocontrolled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc. Drugs Ther. 12:347-53
162. Skarlovnik A, JanicM, LunderM, TurkM, SabovѤcM. 2014. CoenzymeQ10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study. Med. Sci. Monit. 20:2183-88
163. Sohal RS, Kamzalov S, Sumien N, Ferguson M, Rebrin I, et al. 2006. Effect of coenzyme Q10 intake on endogenous coenzyme Q content, mitochondrial electron transport chain, antioxidative defenses, and life span of mice. Free Radic. Biol. Med. 40:480-87
164. Somaratne JB, Berry C, McMurray JJ, Poppe KK, Doughty RN, Whalley GA. 2009. The prognostic significance of heart failure with preserved left ventricular ejection fraction: a literature-based metaanalysis. Eur. J. Heart Fail. 11:855-62
165. Sontag TJ, Parker RS. 2002. Cytochrome P450ε-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. J. Biol. Chem. 277:25290-96
166. Stewart S. 2003. Prognosis of patients with heart failure compared with common types of cancer. Heart Fail. Monit. 3:87-94
167. Stocker R, Bowry VW, Frei B. 1991. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does α-tocopherol. PNAS 88:1646-50
168. Stocker R, Keaney JF Jr. 2004. Role of oxidative modifications in atherosclerosis. Physiol. Rev. 84:1381-478
169. Stocker R, Pollicino C, Gay CA, Nestel P, Colquhoun D, et al. 2006. Neither plasma coenzyme Q10 concentration, nor its decline during pravastatin therapy, is linked to recurrent cardiovascular disease events: a prospective case-control study from the LIPID study. Atherosclerosis 187:198-204
170. Storch A, Jost WH, Vieregge P, Spiegel J, Greulich W, et al. 2007. Randomized, double-blind, placebocontrolled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch. Neurol. 64:938-44
171. Strazisar M, FirM, Golc-Wondra A, Milivojevic L, ProsekM, Abram V. 2005. Quantitative determination of coenyzme Q10 by liquid chromatography and liquid chromatography/mass spectrometry in dairy products. J. AOAC Intl. 88:1020-27
172. Taggart DP, Jenkins M, Hooper J, Hadjinikolas L, Kemp M, et al. 1996. Effects of short-term supplementation with coenzyme Q10 on myocardial protection during cardiac operations. Ann. Thorac. Surg. 61:829-33
173. Takahashi S, Ohtani T, Satoh H, Nakamura Y, Kawamukai M, Kadowaki K-I. 2010. Development of coenzyme Q10-enriched rice using sugary and shrunken mutants. Biosci. Biotechnol. Biochem. 74:182-84
174. Takahashi T, Okuno M, Okamoto T, Kishi T. 2008. NADPH-dependent coenzyme Q reductase is the main enzyme responsible for the reduction of non-mitochondrial CoQ in cells. Biofactors 32:59-70
175. Takimoto M, Sakurai T, Kodama K, Yokoi H, Suzuki Y, et al. 1982. Protective effect of CoQ10 administration on cardial toxicity in FAC therapy. Gan To Kagaku Ryoho 9:116-21
176. Tanaka J, Tominaga R, Yoshitoshi M, Matsui K, Komori M, et al. 1982. CoenzymeQ10: the prophylactic effect on low cardiac output following cardiac valve replacement. Ann. Thorac. Surg. 33:145-51
177. Taylor BA, Lorson L,White CM, Thompson PD. 2015. A randomized trial of coenzymeQ10 in patients with confirmed statin myopathy. Atherosclerosis 238:329-35
178. Teclebrhan H, Olsson J, Swiezewska E, Dallner G. 1993. Biosynthesis of the side chain of ubiquinone:trans-prenyltransferase in rat liver microsomes. J. Biol. Chem. 268:23081-86
179. Thelin A, Schedin S, Dallner G. 1992. Half-life of ubiquinone-9 in rat tissues. FEBS Lett. 313:118-20
180. Tiano L, Belardinelli R, Carnevali P, Principi F, Seddaiu G, Littarru GP. 2007. Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischaemic heart disease: a double-blind, randomized controlled study. Eur. Heart J. 28:2249-55
181. Tomono Y, Hasegawa J, Seki T, Motegi K, Morishita N. 1986. Pharmacokinetic study of deuteriumlabelled coenzyme Q10 in man. Int. J. Clin. Pharmacol. Ther. Toxicol. 24:536-41
182. Tran UC,Clarke CF. 2007. Endogenous synthesis of coenzymeQin eukaryotes. Mitochondrion 7:S62-71
183. UsuiT, IshikuraH, Izumi Y, KonishiH,DohmaeN, et al. 1982. Possible prevention from the progression of cardiotoxicity in adriamycin-treated rabbits by coenzyme Q10. Toxicol. Lett. 12:75-82
184. vanDalen EC, CaronHN, DickinsonHO, Kremer LC. 2011. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst. Rev. 6:CD003917
185. van Heerebeek L, Hamdani N, Falcao-Pires I, Leite-Moreira AF, Begieneman MP, et al. 2012. Low myocardial protein kinaseGactivity in heart failure with preserved ejection fraction. Circulation 126:830-39
186. Vargiu R, Littarru GP, Faa G, Mancinelli R. 2008. Positive inotropic effect of coenzyme Q10, omega-3 fatty acids and propionyl-L-carnitine on papillary muscle force-frequency responses of BIO TO-2 cardiomyopathic Syrian hamsters. Biofactors 32:135-44
187. Verma DD, HartnerWC, ThakkarV, LevchenkoTS, Torchilin VP. 2007. Protective effect of coenzyme Q10-loaded liposomes on the myocardium in rabbits with an acute experimental myocardial infarction. Pharm. Res. 24:2131-37
188. Villalba JM, Parrado C, Santos-Gonzalez M, Alcain FJ. 2010. Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations. Expert Opin. Investig. Drugs 19:535-54
189. Watson PS, Scalia GM, Galbraith A, Burstow DJ, Bett N, Aroney CN. 1999. Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J. Am. Coll. Cardiol. 33:1549-52
190. Wilkinson EG, Arnold RM, Folkers K, Hansen I, Kishi H. 1975. Bioenergetics in clinical medicine. II. Adjunctive treatment with coenzyme Q in periodontal therapy. Res. Commun. Chem. Pathol. Pharmacol. 12:111-23
191. Yamamoto Y, Yamashita S. 1997. Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. Molec. Aspects Med. 18:s79-84
192. Yamamura Y. 1977. Clinical status of coenzyme Q and prospects. In Biomedical and Clinical Aspects of Coenzyme Q, ed. K Folkers, Y Yamamura, pp. 281-98. Amsterdam: Elsevier
193. Yokoyama H, Lingle DM, Crestanello JA, Kamelgard J, Kott BR, et al. 1996. Coenzyme Q10 protects coronary endothelial function from ischemia reperfusion injury via an antioxidant effect. Surgery 120:189-96
194. Young JM, Florkowski CM,Molyneux SL, McEwan RG, Frampton CM, et al. 2007. Effect of coenzyme Q10 supplementation on simvastatin-induced myalgia. Am. J. Cardiol. 100:1400-3
195. Zhang Y, Aberg F, Appelkvist E-L, Dallner G, Ernster L. 1995. Uptake of dietary coenzyme Q supplement is limited in rats. J. Nutr. 125:446-53
196. Zhang Y, Appelkvist E-L, Kristensson K, Dallner G. 1996. The lipid compositions of different regions of rat brain during development and aging. Neurobiol. Aging 17:869-75
197. Zhang Y, Turunen M, Appelkvist E-L. 1996. Restricted uptake of dietary coenzyme Q is in contrast to the unrestricted uptake of α-tocopherol into rat organs and cells. J. Nutr. 126:2089-97
198. Zhou M, Zhi Q, Tang Y, Yu D, Han J. 1999. Effects of coenzyme Q10 on myocardial protection during cardiac valve replacement and scavenging free radical activity in vitro. J. Cardiovasc. Surg. (Torino) 40:355-61