Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations

Expert Opinion on Investigational Drugs

Volumn 19, Issue 4, 2010, Pages 535-554

  Villalba, Jose M ^a   Parrado, Cristina ^a   Santos Gonzalez, Monica ^a   Alcain, Francisco J ^a,b  

^a UNIVERSITY OF CÓRDOBA   (Spain)

^b UNIVERSITY OF CASTILLA LA MANCHA   (Spain)

Author keywords

Coenzyme Q; Coenzyme Q formulations; Idebenone; MitoQ

Indexed keywords

ALPHA TOCOPHEROL; ANTIOXIDANT; BIOQUINON; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IDEBENONE; KANEKA QH; LIQ 10; MITOQUINONE; PLACEBO; PURESORB Q; Q GEL; Q NOL; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); REMACEMIDE; SIMVASTATIN; UBIDECARENONE; UBIQGEL; UNCLASSIFIED DRUG; VITAL; UBIQUINONE;

ADJUVANT THERAPY; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ATAXIA; BRAIN INFARCTION; CARCINOGENESIS; CARDIOVASCULAR DISEASE; CEREBELLAR ATAXIA; CLINICAL TRIAL; DEGENERATIVE DISEASE; DIABETES MELLITUS; DIET SUPPLEMENTATION; DISEASE SEVERITY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FORMULATION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; ENCEPHALOMYOPATHY; ENZYME DEFICIENCY; GASTROINTESTINAL SYMPTOM; HEART LEFT VENTRICLE HYPERTROPHY; HUMAN; HUNTINGTON CHOREA; HYPERCHOLESTEROLEMIA; KIDNEY FAILURE; MALIGNANT NEOPLASTIC DISEASE; MUSCLE DISEASE; NAUSEA; NEUROPROTECTION; NONHUMAN; OXIDATION REDUCTION STATE; PARKINSON DISEASE; PROGRESSIVE SUPRANUCLEAR PALSY; REPEATED DRUG DOSE; RESPIRATORY CHAIN; REVIEW; SINGLE DRUG DOSE; TISSUE DISTRIBUTION; ANIMAL; CARDIOVASCULAR DISEASES; CHEMISTRY; DEFICIENCY; ENZYMOLOGY; GENETICS; MEDICINAL CHEMISTRY; NEURODEGENERATIVE DISEASES; PROCEDURES;

ANIMALS; CARDIOVASCULAR DISEASES; CHEMISTRY, PHARMACEUTICAL; HUMANS; NEURODEGENERATIVE DISEASES; UBIQUINONE;

EID: 77952518304     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543781003727495     Document Type: Review

References (211)

1. Crane FL, Hatefi Y, Lester RL, Widmer C. Isolation of a quinone from beef heart mitochondria. Biochim Biophys Acta 1957;25:220-221
2. Wolf DE, HoVman CH, Trenner NR, et al. Coenzyme Q. Structure studies on the coenzyme Q group. J Am Chem Soc 1958;80:4750-4752
3. Crane FL. Biochemical functions of Coenzyme Q10. J Am Coll Nutr 2001;20:591-598
4. Villalba JM, Navarro F, Cordoba F, et al. Coenzyme Q reductase from liver plasma membrane: purification and role in trans-plasma-membrane electron transport. Proc Natl Acad Sci USA 1995;92:4887-4891
5. Navarro F, Villalba JM, Crane FL, et al. A phospholipid-dependent NADH-coenzyme Q reductase from liver plasma membrane. Biochem Biophys Res Commun 1995;212:138-143
6. Stocker R, Bowry VW, Frei B. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci USA 1991;88:1646-1650
7. Walter L, Nogueira V, Leverve X, et al. Three classes of ubiquinone analogs regulate the mitochondrial permeability transition pore through a common site. J Biol Chem 2000;275:29521-29527
8. Martin SF, Navarro F, Forthoffer N, et al. Neutral magnesium-dependent sphingomyelinase from liver plasma membrane: purification and inhibition by ubiquinol. J Bioenerg Biomembr 2001;33:143-153
9. Kaikkonen J, Nyyssonen K, Porkkala-Sarataho E, et al. Effect of oral coenzyme Q10 supplementation on the oxidation resistance of human VLDL+LDL fraction: absorption and antioxidative properties of oil and granule-based preparations. Free Radic Biol Med 1997;22:1195-1202
10. Santos-González M, Gómez-D́?az C, Navas P, Villalba JM. Modifications of plasma proteome in long-lived rats fed on a coenzyme Q10-supplemented diet. Exp Gerontol 2007;42:798-806
11. Groneberg DA, Kindermann B, Althammer M, et al. Coenzyme Q10 affects expression of genes involved in cell signalling, metabolism and transport in human CaCo-2 cells. Int J Biochem Cell Biol 2005;37:1208-1218
12. Schmelzer C, Kitano M, Rimbach G, et al. Effects of ubiquinol-10 on microRNA-146a expression in vitro and in vivo. Mediators Inflamm 2009;2009:415437
13. Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004;1660:171-199
14. Quinzii CM, DiMauro S, Hirano M. Human coenzyme Q deficiencies. Neurochem Res 2007;32:723-727
15. Forsgren M, Attersand A, Lake S, et al. Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ. Biochem J 2004;382:519-526
16. Casarin A, Jimenez-Ortega JC, Trevisson E, et al. Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis. Biochem Biophys Res Commun 2008;372:35-39
17. Tran UT, Clarke CF. Endogenous synthesis of coenzyme Q in eukaryotes. Mitochondrion 2007;7S:S62-71
18. Herman MD, Alcá?n FJ, Buron MI, et al. Subcellular distribution and biosynthesis of ubiquinone in rat liver. Biol Cell 2001;93:342
19. Fernandez-Ayala DJ, Brea-Calvo G, Lopez-Lluch G, Navas P. Coenzyme Q distribution in HL-60 human cells depends on the endomembrane system. Biochim Biophys Acta 2005;1713:129-137
20. Aberg F, Appelkvist EL, Dallner G, Ernster L. Distribution and redox state of ubiquinones in rat and human tissues. Arch Biochem Biophys 1992;295:230-234
21. Runquist M, Parmryd I, Thelin A, et al. Distribution of branch-point prenyltransferases in regions of bovine brain. J Neurochem 1995;65:2299-2306
22. Naini A, Lewis VJ, Hirano M, DiMauro S. Primary coenzyme Q10 deficiency and the brain. Biofactors 2003;18:145-152 (Pubitemid 38030709)
23. Elmberger PG, Kalen A, Appelkvist EL, Dallner G. In vitro and in vivo synthesis of dolichol and other main mevalonate products in various organs of the rat. Eur J Biochem 1987;168:1-11
24. Molyneux SL, Florkowski CM, Lever M, George PM. Biological variation of coenzyme Q10. Clin Chem 2005;51:455-457
25. Dallner G, Sindelar PJ. Regulation of ubiquinone metabolism. Free Radic Biol Med 2000;29:285-294
26. Aberg F, Zhang Y, Teclebrhan H, et al. Increases in tissue levels of ubiquinone in association with peroxisome proliferation. Chem Biol Interact 1996;99:205-218
27. Brea-Calvo G, Rodŕ?guez-Hernandez A, Fernandez-Ayala DJ, et al. Chemotherapy induces an increase in coenzyme Q10 levels in cancer cell lines. Free Radic Biol Med 2006;40:1293-1302
28. Brea-Calvo G, Siendones E, Sanchez-Alcazar JA, et al. Cell survival from chemotherapy depends on NF-kappaB transcriptional up-regulation of coenzyme Q biosynthesis. PLoS One 2009;4:e5301
29. Bhagavan HN, Chopra RK. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res 2006;40:445-453
30. Beal MF. Coenzyme Q administration and its potential for treatment of neurodegenerative diseases. Biofactors 1999;9:261-266
31. Weber C, Bysted A, Hølmer G. Coenzyme Q10 in the diet-daily intake and relative bioavailability. Mol Aspects Med 1997;18:S251-4
32. Zhang Y, Aberg F, Appelkvist EL, et al. Uptake of dietary coenzyme Q supplement is limited in rats. J Nutr 1995;125:446-453
33. Bhagavan HN, Chopra RK, Craft NE, et al. Assessment of coenzyme Q10 absorption using an in vitro digestion-Caco-2 cell model. Int J Pharm 2007;333:112-117
34. Ochiai A, Itagaki S, Kurokawa T, et al. Improvement in intestinal coenzyme Q10 absorption by food intake. Yakugaku Zasshi 2007;127:1251-1254
35. Kwong LK, Kamzalov S, Rebrin I, et al. Effects of coenzyme Q10 administration on its tissue concentrations, mitochondrial oxidant generation, and oxidative stress in the rat. Free Radic Biol Med 2002;33:627-638
36. Hosoe K, Kitano M, Kishida H, et al. Study on safety and bioavailability of ubiquinol (Kaneka QH) after single and 4-week multiple oral administration to healthy volunteers. Regul Toxicol Pharmacol 2007;47:19-28
37. Weis M, Mortensen SA, Rassing MR, et al. Bioavailability of four oral coenzyme Q10. formulations in healthy volunteers. Mol Aspects Med 1994;15:s273-80
38. Liu ZX, Artmann C. Relative bioavailability comparison of different coenzyme Q10 formulations with a novel delivery system. Altern Ther Health Med 2009;15:42-46
39. Zmitek J, Smidovnik A, Fir M, et al. Relative bioavailability of two forms of a novel water soluble CoQ10. Ann Nutr Metab 2008;52:281-287
40. Kemijski Inst [SI]. Beta-cyclodextrin, process of preparing, and use thereof. EP1755683; 2007
41. Nukui K, Yamagishi T, Miyawaki H, et al. Comparison of uptake between PureSorb-Q40 and regular hydrophobic coenzyme Q10 in rats and humans after single oral intake. J Nutr Sci Vitaminol 2007;53:187-190
42. Ikematsu H, Nakamura K, Harashima S, et al. Safety assessment of coenzyme Q10 (Kaneka Q10) in healthy subjects: a double-blind, randomized, placebo-controlled trial. Regul Toxicol Pharmacol 2006;44:212-218
43. Nakamura T, Ohno T, Hamamura K, Sato T. Metabolism of coenzyme Q10: biliary and urinary excretion study in guinea pigs. Biofactors 1999;9:111-119
44. Palamakula A, Khan MA. Evaluation of cytotoxicity of oils used in coenzyme Q10 Self-Emulsifying Drug Delivery Systems (SEDDS). Int J Pharm 2004;273:63-73
45. Sigma Tau Healthscience Spa. Ubiquinone-containing composition suitable for promoting enhanced intramitochondrial transportation of ubiquinones and methods of using same. WO0023069; 2000
46. Miles MV, Horn P, Miles L, et al. Bioequivalence of coenzyme Q10 from over-the-counter supplements. Nutr Res 2002;22:919-929
47. Ingredient Innovations Interna. Stable aqueous dispersion of nutrients. US6455072; 2002
48. Chopra RK. Reduced form of Coenzyme Q in high bioavailability stable oral dosage form. US6740338; 2004
49. Biosytes USA, Inc. Method for enhancing dissolution properties of relatively insoluble dietary supplements and product incorporating same. US6056971; 2000
50. Molyneux S, Florkowski C, Lever M, George P. The bioavailability of coenzyme Q10 supplements available in New Zealand differs markedly. NZ Med J 2004;117:U1108
51. Nisshin Pharma Inc. Coenzyme Q10-containing water-soluble compositions. WO2007080787; 2007
52. Vesifact AG. Conzyme Q10 containing microemulsion preconcentrates and microemulsions. HK1068806; 2007
53. Wajda R, Zirkel J, Schaffer T. Increase of bioavailability of coenzyme Q10 and vitamin E. J Med Food 2007;10:731-734
54. Lipoid Gmbh Emulsive water-soluble concentrates. KR20050096919; 2005
55. Constantinescu R, McDermott MP, Dicenzo R, et al. A randomized study of the bioavailability of different formulations of coenzyme Q10 (ubiquinone). J Clin Pharmacol 2007;47:1580-1586
56. Hidaka T, Fujii K, Funahashi I, et al. Safety assesment of coenzyme Q10 (CoQ). Biofactors 2008;32:199-208
57. Kitano M, Mizuhashi F, Kubo H, et al. Evaluation of the mutagenic and genotoxic potential of ubiquinol. Int J Toxicol 2007;26:533-544
58. Sumien N, Heinrich KR, Shetty RA, et al. Prolonged intake of coenzyme Q10 impairs cognitive functions in mice. J Nutr 2009;139:1926-1932
59. Boitier E, Degoul F, Desguerre I, et al. A case of mitochondrial encephalomyopathy associated with a muscle coenzyme Q10 deficiency. J Neurol Sci 1998;156:41-46
60. Rotig A, Appelkvist EL, Geromel V, et al. Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency. Lancet 2000;356:391-395
61. Lamperti C, Naine A, Hirano M, et al. Cerebellar ataxia and coenzyme Q10 deficiency. Neurology 2003;60:1206-1208
62. Ogasahara S, Engel AG, Frens D, Mack D. Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. Proc Natl Acad Sci USA 1989;86:2379-2382
63. DiMauro S, Quinzii CM, Hirano M. Mutations in coenzyme Q10 biosynthetic genes. J Clin Invest 2007;117:587-589
64. Quinzii C, Naini A, Salviati L, et al. A mutation in para- hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency. Am J Hum Genet 2006;78:345-349
65. Lopez LC, Schuelke M, Quinzii CM, et al. Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations. Am J Hum Genet 2006;79:1125-1129
66. Mollet J, Giurgea I, Schlemmer D, et al. Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. J Clin Invest 2007;117:765-772
67. Lagier-Tourenne C, Tazir M, Lopez LC, et al. ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. Am J Hum Genet 2008;82:661-672
68. Mollet J, Delahodde A, Serre V, et al. CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures. Am J Hum Genet 2008;82:623-630
69. Duncan AJ, Bitner-Glindzicz M, Meunier B, et al. A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease. Am J Hum Genet 2009;84:558-566
70. Quinzii CM, Lopez LC, Von-Moltke J, et al. Respiratory chain dysfunction and oxidative stress correlate with severity of primary CoQ10 deficiency. FASEB J 2008;22:1874-1885
71. Lopez-Martin JM, Salviati L, Trevisson E, et al. Missense mutation of the COQ2 gene causes defects of bioenergetics and de novo pyrimidine synthesis. Hum Mol Genet 2007;16:1091-1097
72. Quinzii CM, Kattah AG, Naini A, et al. Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Neurology 2005;64:539-541
73. Gempel K, Topaloglu H, Talim B, et al. The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring flavoprotein dehydrogenase (ETFDH) gene. Brain 2007;130:2037-2044
74. Cooper JM, Korlipara LV, Hart PE, et al. Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy. Eur J Neurol 2008;15:1371-1379
75. Marcoff L, Thompson PD. The role of coenzyme Q10 in statin-associated myopathy. J Am Coll Cardiol 2007;49:2231-2237
76. Ghirlanda G, Oradei A, Manto A, et al. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol 1993;33:226-229
77. Berthold HK, Naini A, Di Mauro S, et al. Effect of ezetimibe and/or simvastatin on coenzyme Q10 levels in plasma: a randomised trial. Drug Saf 2006;29:703-712
78. Kalen A, Appelkvist EL, Dallner G. Age-related changes in the lipid compositions of rat and human tissues. Lipids 1989;24:579-584
79. Miles MV, Horn PS, Tang PH, et al. Age-related changes in plasma coenzyme Q10 concentrations and redox state in apparently healthy children and adults. Clin Chim Acta 2004;347:139-144
80. Wada H, Goto H, Hagiwara S, Yamamoto Y. Redox status of coenzyme Q10 is associated with chronological age. J Am Geriatr Soc 2007;55:1141-1142
81. Sohal RJ, Forster MJ. Coenzyme Q, oxidative stress and aging. Mitochondrion 2007;7S:S103-11
82. Folkers K, Osterborg A, Nylander M, et al. Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 1997;234:296-299
83. Mano T, Iwase K, Hayashi R, et al. Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders. Am J Med Sci 1998;315:230-232
84. Portakal O, Ozkaya O, Erden Inal M, et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 2000;33:279-284
85. Jolliet P, Simon N, Barre J, et al. Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. Int J Clin Pharmacol Ther 1998;36:506-509
86. Rusciani L, Proietti I, Paradisi A, et al. Recombinant interferon alpha-2b and coenzyme Q10 as a postsurgical adjuvant therapy for melanoma: a 3-year trial with recombinant interferon-alpha and 5-year follow-up. Melanoma Res 2007;17:177-183
87. Yamamoto Y, Yamashita S, Fujisawa A, et al. Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochem Biophys Res Commun 1998;247:166-170
88. Salviati L, Sacconi S, Murer L, et al. Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: a CoQ10-responsive condition. Neurology 2005;65:606-608
89. Artuch R, Brea-Calvo G, Briones P, et al. Cerebellar ataxia with coenzyme Q10 deficiency: diagnosis and follow-up after coenzyme Q10 supplementation. J Neurol Sci 2006;246:153-158
90. Di Giovanni S, Mirabella M, Spinazzola A, et al. Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency. Neurology 2001;57:375-376
91. Mancuso M, Orsucci D, Volpi L, et al. Coenzyme Q10 in neuromuscular and neurodegenerative disorders. Curr Drug Targets 2010;11:111-121
92. Young AJ, Johnson S, Steffens DC, et al. Coenzyme Q10: a review of its promise as a neuroprotectant. CNS Spectr 2007;12:62-68
93. Laxdale Ltd. Coenzyme Q and eicosapentaenoic acid (EPA). NZ529339; 2004
94. US Dept Veterans Affairs, Method of ameliorating or abrogating the effects of a neurodegenerative disorder, such as Huntington's disease, by using coenzyme Q10. US2006078549; 2006
95. US Dept of Veterans Affairs, Method of ameliorating or abrogating the effects of a neurodegenerative disorder, such as Huntington's disease, by sodium butyrate chemotherapy. US2006069157; 2006
96. Kanegafuuchi Chem Ind. agent for improving nervous system cell functions. EP2005951; 2008
97. Kunming Xianghao Tec Co [CN]. Lycopene and coenzyme Q10 containing formulation and its manufacturing method. CN1634075; 2005
98. Delanty N, Dichter MA. Oxidative injury in the nervous system. Acta Neurol Scand 1998;98:145-153
99. Feigin A, Kieburtz K, Como P, et al. Assessment of coenzyme Q10 tolerability in Huntington's disease. Mov Disord 1996;11:321-323
100. Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF. Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann Neurol 1997;41:160-165
101. Ferrante RJ, Andreassen OA, Dedeoglu A, et al. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J Neurosci 2002;22:1592-1599
102. Yang L, Calingasan NY, Wille EJ, et al. Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseases. J Neurochem 2009;109:1427-1439
103. Huntington Study Group. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington's disease. Neurology 2001;57:397-404
104. Aylward EH, Rosenblatt A, Field K, et al. Caudate volume as an outcome measure in clinical trials for Huntington's disease: a pilot study. Brain Res Bull 2003;62:137-141
105. Shults CW. Therapeutic role of coenzyme Q10 in Parkinson's disease. Pharmacol Ther 2005;107:120-130
106. Sohmiya M, Tanaka M, Tak NW, et al. Redox status of plasma coenzyme Q10 indicates elevated systemic oxidative stress in Parkinson's disease. J Neurol Sci 2004;223:161-166
107. Gotz ME, Gerstner A, Harth R, et al. Altered redox state of platelet coenzyme Q10 in Parkinson's disease. J Neural Transm 2000;107:41-48
108. Samii A, Carleton BC, Etminan M. Statin use and the risk of Parkinson disease: a nested case control study. J Clin Neurosci 2008;15:1272-1273
109. Cleren C, Yang L, Lorenzo B, et al. Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of Parkinsonism. J Neurochem 2008;104:1613-1621
110. Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 2002;59:1541-1550
111. Müller T, Büttner T, Gholipour AF, Kuhn W. Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson's disease. Neurosci Lett 2003;341:201-204
112. Shults CW, Flint Beal M, Song D, Fontaine D. Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson's disease. Exp Neurol 2004;188:491-494
113. MSE Pharmazeutica Gmb. Particles with modified physicochemical properties, their preparation and uses. EP0711151; 1996
114. Storch A, Jost WH, Vieregge P, et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch Neurol 2007;64:938-944
115. Stamelou M, Reuss A, Pilatus U, et al. Short-term effects of coenzyme Q10 in progressive supranuclear palsy: a randomized, placebo-controlled trial. Mov Disord 2008;23:942-949
116. Wadsworth TL, Bishop JA, Pappu AS, et al. Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease. J Alzheimers Dis 2008;14:225-234
117. Molina JA, de Bustos F, Jiménez-Jiménez FJ, et al. Serum levels of coenzyme Q10 in patients with amyotrophic lateral sclerosis. J Neural Transm 2000;107:1021-1026
118. Sohmiya M, Tanaka M, Suzuki Y, et al. An increase of oxidized coenzyme Q10 occurs in the plasma of sporadic ALS patients. J Neurol Sci 2005;228:49-53
119. Ferrante KL, Shefner J, Zhang H, et al. Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS. Neurology 2005;65:1834-1836
120. Traynor BJ, Bruijn L, Conwit R, et al. Neuroprotective agents for clinical trials in ALS: a systematic assessment. Neurology 2006;67:20-27
121. Kaufmann P, Thompson JL, Levy G, et al. Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III. Ann Neurol 2009;66:235-244
122. Siddiqi SA, Thompson PD. How do you treat patients with myalgia who take statins? Curr Atheroscler Rep 2009;11:9-14
123. Lamperti C, Naini AB, Lucchini V, et al. Muscle coenzyme Q10 level in statin-related myopathy. Arch Neurol 2005;62:1709-1712
124. Paiva H, Thelen KM, Van Coster R, et al. High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. Clin Pharmacol Ther 2005;78:60-68
125. Schick BA, Laaksonen R, Frohlich JJ, et al. Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin. Clin Pharmacol Ther 2007;81:650-653
126. Kucharska J, Gvozdjakova A, Simko F. Simvastatin decreased coenzyme Q in the left ventricle and skeletal muscle but not in the brain and liver in L-NAME-induced hypertension. Physiol Res 2007;56:S49-54
127. Merck & Co Inc. Coenzyme Q10 with HMG-CoA reductase inhibitors. US4929437; 1990
128. Merck & Co Inc. Coenzyme Q10 with HMG-CoA reductase inhibitors. US4933165;1990
129. Young JM, Florkowski CM, Molyneux SL, et al. Effect of coenzyme Q10 supplementation on simvastatin-induced myalgia. Am J Cardiol 2007;100:1400-1403
130. Reidenberg MM. Statins, lack of energy and ubiquinone. Br J Clin Pharmacol 2005;59:606-607
131. Kanegafushi Chem Ind. Anti-fatigue composition. EP1897539; 2008
132. Folkers K, Simonsen R Two successful double-blind trials with coenzyme Q10 (vitamin Q10) on muscular dystrophies and neurogenic atrophies. Biochim Biophys Acta 1995;1271:281-286
133. Tedeschi D, Lombardi V, Mancuso M, et al. Potential involvement of ubiquinone in myotonic dystrophy pathophysiology: new diagnostic approaches for new rationale therapeutics. Neurol Sci 2000;21:S979-80
134. Miles L, Miles MV, Tang PH, et al. Muscle coenzyme Q: a potential test for mitochondrial activity and redox status. Pediatr Neurol 2005;32:318-324
135. Nisshin Pharma Inc (JP). Therapeutics for muscular dystrophy and therapeutic foods therefor. WO2004075908; 2004
136. Folkers K, Vadhanavikit S, Mortensen SA. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci USA 1985;82:901-904
137. Langsjoen PH, Langsjoen A, Willis R, Folkers K. Treatment of hypertrophic cardiomyopathy with coenzyme Q10. Mol Aspects Med 1997;18:S145-51
138. Univ Texas. Restoration of impaired cardiac function of patients with diverse muscular dystrophies by therapy with coenzyme Q10. US4885167; 1989
139. Lifepharma Srl. Pharmaceutical or dietary composition having vigorous antioxidant activity in cardiovascular and/or liver diseases. IT1255230; 1995
140. Molyneux SL, Florkowski CM, George, et al. Coenzyme Q10: an independent predictor of mortality in chronic heart failure. J Am Coll Cardiol 2008;52:1435-1441
141. Pepe S, Marasco SF, Haas SJ, et al. Coenzyme Q10 in cardiovascular disease. Mitochondrion 2007:S154-67
142. Kumar A, Kaur H, Devi P, Mohan V. Role of coenzyme Q10 (CoQ10) in cardiac disease, hypertension and Meniere-like syndrome. Pharmacol Ther 2009;124(3):259-268
143. Langsjoen PH, Langsjoen AM. Supplemental ubiquinol in patients with advanced congestive heart failure. Biofactors 2008;32:119-128
144. Hadj A, Esmore D, Rowland M, et al. Pre-operative preparation for cardiac surgery utilising a combination of metabolic, physical and mental therapy. Heart Lung Circ 2006;15:172-181
145. Pepe S, Leong JY, Van der Merwe J, et al. Targeting oxidative stress in surgery: effects of ageing and therapy. Exp Gerontol 2008;43:653-657
146. Makhija N, Sendasgupta C, Kiran U, et al. The role of oral coenzyme Q10 in patients undergoing coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2008;22:832-839
147. Hodgson JM, Watts GF, Playford DA, et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002;56:1137-1142
148. Playford DA, Watts GF, Croft KD, Burke V. Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes. Atherosclerosis 2003;168:169-179
149. Watts GF, Playford DA, Croft KD, et al. Coenzyme Q(10) improves endothelial dysfunction of the brachial artery in type II diabetes mellitus. Diabetologia 2002;45:420-426
150. Chew GT, Watts GF, Davis TM, et al. Hemodynamic effects of fenofibrate and coenzyme Q10 in type 2 diabetic subjects with left ventricular diastolic dysfunction. Diabetes Care 2008;31:1502-1509
151. Hamilton SJ, Chew GT, Watts GF. Coenzyme Q10 improves endothelial dysfunction in statin-treated type 2 diabetic patients. Diabetes Care 2009;32:810-812
152. Tiano L, Belardinelli R, Carnevali P, et al. 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 2007;28:2249-2255
153. Belardinelli R, Tiano L, Littarru GP. Oxidative stress, endothelial function and coenzyme Q10. Biofactors 2008;32:129-133
154. Seuref AG. Pharmaceutical compositions having vasodilating and antianoxic activities. US4778798; 1988
155. Univ Leland Stanford Junior. Enhancement of vascular function by modulation of endogenous nitric oxide production or activity. US2006009407; 2006
156. Tsuneki H, Sekizaki N, Suzuki T, et al. Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells. Eur J Pharmacol 2007;566:1-10
157. Roffe L, Schmidt K, Ernst E. Efficacy of coenzyme Q10 for improved tolerability of cancer treatments: a systematic review. J Clin Oncol 2004;22:4418-4424
158. Premkumar VG, Yuvaraj S, Vijayasarathy K, et al. Effect of coenzyme Q10, riboflavin and niacin on serum CEA and CA 15-3 levels in breast cancer patients undergoing tamoxifen therapy. Biol Pharm Bull 2007;30:367-370
159. Premkumar VG, Yuvaraj S, Vijayasarathy K, et al. Serum cytokine levels of interleukin-1beta,-6,-8, tumour necrosis factor-alpha and vascular endothelial growth factor in breast cancer patients treated with tamoxifen and supplemented with co-enzyme Q10, riboflavin and niacin. Basic Clin Pharmacol Toxicol 2007;100:387-391
160. Premkumar VG, Yuvaraj S, Shanthi P, et al. Co-enzyme Q10, riboflavin and niacin supplementation on alteration of DNA repair enzyme and DNA methylation in breast cancer patients undergoing tamoxifen therapy. Br J Nutr 2008;100:1179-1182
161. Premkumar VG, Yuvaraj S, Sathish S, et al. Anti-angiogenic potential of coenzymeQ10, riboflavin and niacin in breast cancer patients undergoing tamoxifen therapy. Vascul Pharmacol 2008;48:191-201
162. Hoenjet KM, Dagnelie PC, Delaere KP, et al. Effect of a nutritional supplement containing vitamin E, selenium, vitamin C and coenzyme Q10 on serum PSA in patients with hormonally untreated carcinoma of the prostate: a randomised placebo-controlled study. Eur Urol 2005;47:43343-43349
163. Singh RP, Kumar R, Kapur N. Molecular regulation of cholesterol biosynthesis: implications in carcinogenesis. J Environ Pathol Toxicol Oncol 2003;22:75-92
164. Kaneka Corp (JP), Japan Government (JP). Composition for prevention of cancer. EP1908459; 2008
165. Kaneka Corp (JP). Method for cancer treatment, carcinogenesis suppression or mitigation of adverse reactions of anticancer agents. US2008138326; 2008
166. Kucharská J, Braunová Z, Ulicná O, et al. Deficit of coenzyme Q in heart and liver mitochondria of rats with streptozotocin-induced diabetes. Physiol Res 2000;49:411-418
167. Menke T, Niklowitz P, Wiesel T, Andler W. Antioxidant level and redox status of coenzyme Q10 in the plasma and blood cells of children with diabetes mellitus type 1. Pediatr Diabetes 2008;9:540-545
168. Miles MV, Morrison JA, Horn PS, et al. Coenzyme Q10 changes are associated with metabolic syndrome. Clin Chim Acta 2004;344:173-179
169. Fujii K, Kawabe T, Hosoe K, et al. Compositions for diabetes. US2005113459; 2005
170. Huaibei Huike Pharmaceutical. The compound preparation for treating diabetes mellitus. WO2006102804; 2006
171. Response Scient Inc. Medical food or nutritional supplement, method of manufacturing same, and method of managing diabetes. US2009053303; 2009
172. Mancini A, Conte B, De Marinis L, et al. Coenzyme Q10 levels in human seminal fluid: diagnostic and clinical implications. Mol Aspects Med 1994;15:s249-55
173. Balercia G, Arnaldi G, Fazioli F, et al. Coenzyme Q10 levels in idiopathic and varicocele-associated asthenozoospermia. Andrologia 2002;34:107-111
174. Balercia G, Buldreghini E, Vignini A, et al. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertil Steril 2009;91:1785-1792
175. Lewin A, Lavon H. The effect of coenzyme Q10 on sperm motility and function. Mol Aspects Med 1997;18:S213-9
176. Littarru G, Balercia G. Method for treating and preventing male infertility. US2006154993; 2006
177. Miles MV, Patterson BJ, Chalfonte-Evans ML, et al. Coenzyme Q10 (ubiquinol-10) supplementation improves oxidative imbalance in children with trisomy 21. Pediatr Neurol 2007;37:398-403
178. Tiano L, Padella L, Carnevali P, et al. Coenzyme Q10 and oxidative imbalance in Down syndrome: biochemical and clinical aspects. Biofactors 2008;32:161-167
179. Takeda Chem Ind Ltd. Cerebral circulatory metabolism-improving agent. JP1221316; 1989
180. Geromel V, Darin N, Chrétien D, et al. Coenzyme Q10 and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits. Mol Genet Metab 2002;77:21-30
181. Bodmer M, Vankan P, Dreier M. Pharmacokinetics and metabolism of idebenone in healthy male subjects. Eur J Clin Pharmacol 2009;65:493-501
182. Kutz K, Drewe J, Vankan P. Pharmacokinetic properties and metabolism of idebenone. J Neurol 2009;256:31-35
183. Torii H, Yoshida K, Kobayashi T. Disposition of idebenone (CV-2619), a new cerebral metabolism improving agent, in rats and dogs. J Pharmacobiodyn 1985;8:457-467
184. Haginoya K, Miyabayashi S, Kikuchi M, et al. Efficacy of idebenone for respiratory failure in a patient with Leigh syndrome: a long-term follow-up study. J Neurol Sci 2009;278:112-114
185. Ikejiri Y, Mori E, Ishii K, et al. Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAS. Neurology 1996;47:583-585
186. Napolitano A, Salvetti S, Vista M, et al. Long-term treatment with idebenone and riboflavin in a patient with MELAS. Neurol Sci 2000;21:S981-2
187. Mashima Y, Kigasawa K, Wakakura M, Oguchi Y. Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy? J Neuroophthalmol 2000;20:166-170
188. Carelli V, Valentino ML, Liguori R, et al. Leber's hereditary optic neuropathy (LHON/11778) with myoclonus: report of two cases. J Neurol Neurosurg Psychiatry 2001;71:813-816
189. Barnils N, Mesa E, Muñoz S, et al. Response to idebenone and multivitamin therapy in Leber's hereditary optic neuropathy. Arch Soc Esp Oftalmol 2007;82:377-380
190. Hirai K, Hayako H, Kato K, Miyamoto M. Idebenone protects hippocampal neurons against amyloid beta-peptide-induced neurotoxicity in rat primary cultures. Naunyn Schmiedebergs Arch Pharmacol 1998;358:582-585
191. Takeda Chem Ind. Use of idebenone and analogues against beta amyloid induced cytotoxicity. US6271266; 2001
192. Takeda Chem Ind. Treating and preventing agent for Alzheimer's disease. JP10259126; 1998
193. Takeda Chem Ind. Idebenone compositions for treating Alzheimer's disease. EP0629400; 2000
194. Weyer G, Babej-Dolle RM, Hadler D, et al. A controlled study of 2 doses of idebenone in the treatment of Alzheimer's disease. Neuropsychobiology 1997;36:73-82
195. Gutzmann H, Hadler D. Sustained efficacy and safety of idebenone in the treatment of Alzheimer's disease: update on a 2-year double-blind multicentre study. J Neural Transm Suppl 1998;54:301-310
196. Thal LJ, Grundman M, Berg J, et al. Idebenone treatment fails to slow cognitive decline in Alzheimer's disease. Neurology 2003;61:1498-1502
197. Tonon C, Lodi R. Idebenone in Friedreich's ataxia. Expert Opin Pharmacother 2008;9:2327-2337
198. Dürr A, Cossee M, Agid Y. Clinical and genetic abnormalities in patients with Friedreich's ataxia. N Engl J Med 1996;335:1169-1175
199. Rotig A, de Lonlay P, Chretien D. Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Nat Genet 1997;17:215-217
200. Meier T, Buyse G. Idebenone: an emerging therapy for Friedreich ataxia. J Neurol 2009;256:25-30
201. Inst. Nat. Sante Rech Med. (FR). Quinone derivatives for treating or preventing diseases associated with iron overload. US6133322; 2000
202. Myocontract Ltd. A screening method and compounds for treating Friedreich ataxia. WO2004003565; 2004
203. Di Prospero NA, Baker A, Jeffries N, Fischbeck KH. Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial. Lancet Neurol 2007;6:878-886
204. Pineda M, Arpa J, Montero R, et al. Idebenone treatment in paediatric and
205. Rinaldi C, Tucci T, Maione S, et al. Low-dose idebenone treatment in Friedreich's ataxia with and without cardiac hypertrophy. J Neurol 2009;256:1434-1437
206. Jauslin ML, Meier T, Smith RA, Murphy MP. Mitochondria-targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants. FASEB J 2003;17:1972-1984
207. Murphy MP, Smith RA. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu Rev Pharmacol Toxicol 2007;47:629-656
208. Univ Otago, New Zeeland. Mitochondrially targeted antioxidants. US2004106579; 2004
209. Cocheme HM, Kelso GF, James AM, et al. Mitochondrial targeting of quinones: therapeutic implications. Mitochondrion 2007;7S:S94-102
210. Tauskela JS. MitoQ-a mitochondria-targeted antioxidant. IDrugs 2007;10:399-412
211. Snow BJ, Rolfe FL, Murphy MP. Phase II study of the mitochondrial antioxidant mitoquinone for Parkinson's disease. Proceedings of 60th American Academy of Neurology Annual Meeting; 12-19 April 2008; Chicago