1 Coenzyme Q10 1 Coenzyme Q 10 (Ubiquinone) James Meschino DC, MS, ND General Features CoQ 10 is an essential component of the electron transfer system in the mitochondria. More specifically, it functions to shuttle hydrogen electrons from NAD to cytochrome b, facilitating the release of energy required to recouple ADP with inorganic phosphate in the synthesis of ATP. As such, CoQ 10 is an integral part of the bioenergetic system that enables cells to produce adequate amounts of ATP through aerobic pathways. ATP is the primary fuel required to power the body s metabolic reactions, maintain optimal function of cells and sustain life. A deficit in ATP synthesis can compromise any number of energy-dependent cellular functions and hasten the onset of dysfunction and if severe enough, cell death. Although the body can synthesize CoQ 10, deficiency states of CoQ 10 tend to exist and are associated with various health conditions. Moreover, supplementation studies with CoQ 10 have been shown to effectively treat and sometimes reverse a number of these conditions. There is evidence that a decline in CoQ 10 synthesis occurs with aging, predisposing individuals to a number of CoQ 10 deficiency-related disorders and diseases. Professor F.L. Crane and his colleagues at the University of Wisconsin first discovered CoQ 10 in Since then, Dr, Karl Folkers at the University of Texas (Austin) is most responsible for the ongoing research on CoQ Coenzyme Q 10 is also a fat soluble antioxidant, which has been shown to reduce oxidation of LDL-cholesterol and the mitochondrial DNA. 5,6 CoQ 10 supplementation has been shown to modulate immune system function, enhancing levels of immunoglobulin G (IgG), in the serum of patients provided with 60 mg CoQ 10 per day. 7 The average person may consume about 5 mg per day of CoQ 10 from foods, with the main sources being meat, fish, soybeans and some vegetable oils. Clinical Coenzyme Q 10 studies have involved daily supplemental intake levels ranging from 60 mg to 300 mg per day; far greater than food alone can provide. 8 Supplementation Studies and Clinical Applications 1. Cardiovascular Disease Biopsy results from heart tissue in patients with various cardiovascular diseases (especially congestive heart failure) show a deficiency in CoQ 10 in 50 to 75 percent of cases. Low blood levels of CoQ 10 are also a consistent finding in the majority of these patients Supplementation studies with patients suffering from various cardiomyopathies (i.e. ischemic cardiomyopathy, dilated cardiomyopathy, heart valve disorders) and congestive heart failure have demonstrated significant improvement in heart function (according to the New York Heart Association functional scale) in a high percentage of cases.
2 Coenzyme Q10 2 Many patients in these studies have been able to reduce the number of cardiac drugs required (1-3 medications reduced in 43 percent of CoQ 10 supplemented patients in one study of 424 patients, over an eight year period). Heart function parameters monitored have included left ventricular wall thickness, mitral valve inflow slope, and fractional shortening. 13,14,15 a. Congestive Heart Failure - Several controlled studies using Coenzyme Q 10 supplementation in patients with congestive heart failure have demonstrated significant improvement in cardiac ejection fraction, reduced shortness of breath, and increased muscle strength. Other studies have demonstrated increased stroke volume and cardiac index, improved survival and improved quality of life, in general. Of great significance is the fact that when patients discontinue CoQ 10 supplementation, cardiac function deteriorates. Thus, CoQ 10 needs to be a lifelong intervention in these cases. 16,17,18 b. Angina - A small study has shown that CoQ 10 supplementation can reduce angina episodes and nitroglycerine use and improve treadmill exercise tolerance. Larger trials are required to substantiate this data. 19 c. Hypertension - Several studies have provided evidence that CoQ 10 supplementation can lower systolic and diastolic blood pressure (i.e. systolic , diastolic 98-86) in hypertensive patients. Improved blood cholesterol levels also occurred in one study, with a rise in HDL and a reduction in total cholesterol from mg/dl to mg/dl Periodontal Disease Several intervention trials involving patients with periodontal disease have revealed that CoQ 10 supplementation can be useful in reversing the condition to various degrees. 23,24 3. Aerobic Exercise Performance A study of 25 cross-country skiers has provided preliminary evidence that CoQ 10 supplementation may improve exercise performance in endurance athletes. 25 Sedentary individuals have also demonstrated improvement with work capacity, oxygen consumption, fat burning and oxygen transport after beginning an exercise program. The group supplemented with CoQ 10 demonstrated greater improvement in these aerobic parameters compared to the placebo group, in a 4-8 week trial period. 26 Dosage Ranges 1. Cardiovascular Conditions: typical dosage is mg, three times per day. Large doses (up to 300 mg) may be needed in severe heart disease. Some studies use a dosage of 2 mg CoQ 10 for each kilogram of body weight. 2. Periodontal Disease: 50 mg per day has been used in clinical trials 3. Exercise Performance Studies: 60 mg per day 27 Toxicity and Contraindications Coenzyme Q 10 is well tolerated, and no serious adverse effects have been reported with longterm use. 27
3 Coenzyme Q10 3 Drug-Nutrient Interactions 1. Warfarin CoQ 10 supplementation has been shown to antagonize the anti-coagulant effects of warfarin, requiring dose adjustment. 2. Beta-Blockers and HMG CoA Reductase (statin) drugs for cholesterol lowering are known to inhibit the endogenous synthesis of CoQ 10. CoQ 10 supplementation can compensate for this inhibition effect and is indicated as a concurrent therapy when these drugs are in use (100 mg of CoQ 10 per day is recommended in these cases). 3. Psychotropic Drugs Coenzyme Q 10 supplementation has been shown to reduce the cardiac side effects of phenothiazines and tricyclic antidepressant drugs. 4. Chemotherapy Q 10 supplementation can mitigate the cardiac side effects and cardiotoxicity of the chemotherapy drug known as adriamycin (100 mg per day of CoQ10 supplementation). Even children with lymphoblastic leukemia or non-hodgkin lymphoma realized this benefit compared with the placebo group Anticoagulants As noted above, there are reported cases of CoQ 10 countering the action of warfarin. Thus, the physician prescribing warfarin may need to adjust the warfarin dose if CoQ 10 is to be used and therefore must be consulted. 34,35 The following drugs may reduce the body s levels of CoQ 10 : 1. Orlistat: reduces CoQ 10 absorption Beta blockers: decreases CoQ 10 synthesis Biguanides: decreases CoQ 10 synthesis Clondine: decreases CoQ 10 synthesis Gemfibrozil: (cholesterol-lowering drug) Haloperidol: decreases CoQ 10 synthesis HMG-CoA Reductase inhibitors: decreases CoQ 10 synthesis Hydralazine: decreases CoQ 10 synthesis Methydopa: decreases CoQ 10 synthesis Phenothiazines: decreases CoQ 10 synthesis Sulfonylureas: some of these drugs decrease CoQ 10 synthesis (acetohexamide, glyburide, tolazamide) Thiazide Diuretics: decrease CoQ 10 synthesis Tricyclic Antidepressants: decrease CoQ 10 synthesis. 41
4 Coenzyme Q Folkers K, Yamamura Y, editors. Biomedical and clinical aspects of coenzyme Q. Vol 1. Amsterdam: Elsevier/North-Holland Biomedical Press; Yamamura Y, Folkers K and Ito Y, editors. Biomedical and clinical aspects of coenzyme Q. Vol 2. Amsterdam, Holland; Elsevier/North-Holland Biomedical Press; Folkers K, Yamamura Y, editors. Biomedical and clinical aspects of coenzyme Q. Vol 3. Amsterdam: Elsevier/North-Holland biomedical Press; Folkers K, Yamamura Y, editors. Biomedical and clinical aspects of Coenzyme Q. Vol 4. Amsterdam: Elsevier Science Publ; Frei B, Kim MC, Ames BN. Ubiquinenol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc Natl Acad Sce 1990;87: Weber C, Jakobsen TS, Mortensen SA, Paulsen G, Holmer G. Effect of dietary coenzyme Q10 as an antioxidant in human plasma. Mol Aspects Med 1994;15(Suppl):97S-102S. 7. Folkers K, et al. Increase in levels of lgg in serum of patients treated with coenzyme Q10. Res Commun Chem Pathol Pharnacol 1982;38: Reavely N. New encyclopedia of vitamins, minerals, supplements and herbs. New York: Evans M and Company, Inc.; p Kitamura N, Yamaguchi A, Otaki M, Sawatani O, Minoji T, Tamura H, et al. Mycocardial tissue level of coenzyme Q10 in patients with cardiac failure. In: Folkers K, Yamamura Y, editors. Biomedical and Clinical Aspects of Coenzyme Q, Vol 4. Amsterdam, Holland: Elsvier Science,Publ; p Littarru GP, Ho L, Folkers K. Deficiency of coenzyme Q10 in human heart disease, Part II. Int J Vit Nutr Res 1972;42: Folkders K, et al. Evidence for a deficiency of coenzyme Q10 in human heart disease. Int J Vit Res 1970;40: 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 1985;82: Langsjoen H, Langsjoen P, Langsjoen P, Willis R, Folkers K. Usefulness of coenzyme Q10 in clinical cardiology: A long-term study. Mol Aspects Med 1994;1(Suppl):165S-75S. 14. Tsuyusaki T, Noro C, Kikawada R. Mechanocardiography of ischemic or hypertensive heart failure. In: Yamamura Y, Folkers K, Ito Y, editors. Biomedical and clinical aspects of coenzyme Q. Vol 2. Amsterdam, Holland; Elsevier/North-Holland Biomedical Press; p Judy WV, Hall JT, Toth PD, Folkers K. Myocardial effects of co-enzyme Q10 in primary heart failure. In: Folkers K, Yamamura Y, editors. Biomedical and clinical aspects of Coenzyme Q. Vol 4. Amsterdam: Elsevier Science Publ; p Langsjoen PH, Vadhanavikit S, Folkers K. Response of patients in classes III and IV of cardiomyopathy to therapy in a blind and crossover trial with coenzyme Q10. Proc Natl Acad Sci 1985;82: Morisco C, Trimarco B, Condorelli M. Effect of CoQ10 therapy in patients with congestive heart failure: A long-term multicenter randomized study. Clin Invest 1993;71(Suppl):134S-6S. 18. Baggio E, Gandini R, Plancher AC, Passeri M, Carmosino G. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med 1994;15(Suppl):287S-94S. 19. Kamikawa T, Kobayashi A, Yamashita T, Hayashi H, Yamazaki N. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. Am J Cariol 1985;56: Digiesi V, Cantini F, Brodbeck B. Coenzyme Q10 in essential hypertension. Mol Aspects Med 1994;15(Suppl):257S-63S. 21. Langsjoen P, et al. Treatment of essential hypertension with coenzyme Q10. Mol Aspects Med 1994;15: Digiesi V, Cantini F, Bisi G, et al. Mechanism of action of coenzyme Q10 in essential hypertension. Curr Thes Res 1992;51: Nakamura R, Littrau GP, Folkers K, Wilkinson EG. Study of Co Q10 enzymes in gingiva from patients with periodontal disease and evidence for a deficiency of coenzyme Q10. Proc Natl Acad Sci 1974;71:1456.
5 Coenzyme Q Wilkinson EG, Arnold RM, Folkers K. Treatment of periodontal and other soft tissue diseases of the oral cavity with coenzyme Q10. In: Folkers K, Yamamura Y, editors. Biomedical and clinical aspects of coenzyme Q. Vol 1. Amsterdam: Elsevier/North-Holland Biomedical Press; p Ylikoski T, Piirainen J, Hanninen O, Penttinen J. The effect of coenzyme Q10 on the exercise performance of cross-country skiers. Mol Aspects Med 1997;18(Suppl):283S-90S. 26. Vanfraechem JHP, Folkers K. Coenzyme Q10 and physical performance. In: Folkers K, Yamamura Y, editors. Biomedical and clinical aspects of coenzyme Q. Vol 3. Amsterdam: Elsevier/North-Holland biomedical Press; p Murry M. Encyclopedia of Nutritional Supplements. Rocklin, CA: Prima Publishing; p Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductate inhibitors. Mol Aspects Med 1997;18(Suppl):137S-44S. 29. Bargossi AM, Grossi G, Fiorella PL, Gaddi A, Di Giulio R, Battino M. Exogenous CoQ10 supplementation prevents plasma ubiquinone reduction induced by HMG-CoA reductate inhibitors. Mol Aspects Med 1994;15(Suppl):187S-93S. 30. Hamada M, Kazarani Y, Ochi T, Ito T, Kokubu T. Correlatio between serum CoQ10 level and myocordiol contractility in hypertensive patients. In: Folkers K, Yamamura Y, editors. Biomedical and clinical aspects of Coenzyme Q. Vol 4. Amsterdam: Elsevier Science Publ; p Judy WV, Hall JH, Dugan W, Toth PD, Folkers K. Coenzyme Q10 reduction in adriamycin cardiotoxicity. In: Folkers K, Yamamura Y, editors. Biomedical and clinical aspects of Coenzyme Q. Vol 4. Amsterdam: Elsevier Science Publ; p Iarussi D, Auricchio U, Agretto A, Murano A, Giuliano M, Casale F, et al. Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: Control study in children with acute lyphhoblastic leukemia and non- Hodgkin lymphoma. Mol Aspects Med, 1994;15(Suppl):207S-12S. 33. Kishi T, Makino K, Okamoto T, Kishi H, Folkers K. Inhibition of myocardial respiration by psychotherapeutic drugs and prevention by coenzyme Q. In: Yamamura Y, Folkers K and Ito Y, editors. Biomedical and clinical aspects of coenzyme Q. Vol 2. Amsterdam, Holland; Elsevier/North-Holland Biomedical Press; Pg Heck AM, Deweitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57(13): Landbo C, Almdal TP. Interaction between warfarin and coenzyme Q 10. Ugeskr Laeger. 1998;160(22): Xenical (orlistat), Product Prescribing Information. Nutley, NJ: Roche Laboratories, Inc., Sept Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q 10 - enzymes by clinically used adrenergic blockers of beta-receptors. Res Commun Chem Pathol Pharmacol. 1977;17(1): Kishi T, Kishi H, Watanabe T, Folkers K. Bioenergetics in clinical medicine XI. Studies on coenzyme Q and Diabetes Mellitus. J Med 1976;7(3): Kishi H, Kishi T, Folkers K. Bioenergetics in clinical medicine. III. Inhibition of coenzyme Q 10 -enzymes by clinically used anti-hypertensive drugs. Res Commun Chem Pathol Pharmacol 1975;12(3): Aberg F, Appelkvist EL, Bröijersén A, Eriksson M, Angelin B, Hjemdahl P, et al. Gemfibrozil-induced decrease in serum Ubiquinone and alpha- and gamma-tocopherol levels in men with combined hyperlipidaemia. Eur J Clin Invest 1998;28(3): Kishi T, Makino K, Okamoto T, Kishi H, Folkers K. Inhibition of myocardial respiration by psychotherapeutic drugs and prevention by coenzyme Q 10. In: Biomedical and clinical aspects of coenzyme Q 10. Yamamura Y, Folkers K, Ito Y, editors. Vol 2. Amsterdam: Elsevier/North-Holland Biomedical Press; p Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, et al. Evidence of plasma Co 10 - lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol 1993;33(3):226-9.