-IBIS-1.7.6-
rx
nutritional supplement
Coenzyme Q10 (ubiquinone)
Nutrition

nutrition

definition

Coenzyme Q10 (ubiquinone):

» chemistry:
• The primary biochemical action of CoQ10 is as a cofactor in the electron-transport chain, a series of oxidation-reduction reactions involved in cellular respiration and the synthesis of ATP.

» metabolism:
• CoQ10 can be synthesized in vivo. However, in some situations the need for CoQ10 may surpass the body’s ability to synthesize it. CoQ10 is well-absorbed by oral supplementation as evidenced by significant increases in serum CoQ10 levels after supplementation. (Gaby AR. Alt Med Rev 1996;1(1): 11-17) There is some evidence that CoQ10 in oil suspension has the highest bioavailability.
(Gaby AR. Alt Med Rev 1996;1(3): 168-175; Kaikkonen J, et al. Free Rad Biol Med 1997;22: 1195-1202.)

» requirements:
• RDA: No RDA has been established.

» deficiency:
• A deficiency may result from:
1. Impaired synthesis due to nutritional deficiencies;
2. Genetic or acquired defect in synthesis or utilization;
3. Increased tissue needs resulting from illness. CoQ10 levels decline with advancing age.

» mode of action:
• CoQ10, due to its involvement in ATP synthesis, affects the function of all cells in the body, making it essential for the health of all human tissues and organs. CoQ10 particularly affects the cells that are the most metabolically active: heart, immune system, gingiva, and gastric mucosa.

» therapeutics:
Allergies: CoQ10 inhibits release of histamine and SRSA in antigen-challenged animals.
(Ishihara Y, et al. Arzneimittelforsch 1985;35 :929-933.)
Cancer: prevents metastasis and enhances remission in breast cancer. (Lockwood K, et al. Molec Aspects Med 1994;15(Suppl):S231-S240; Lockwood K, et al. Biochem Biophys Res Commun 1995:212:172-177) Mechanisms in cancer include immune system enhancement and antioxidant activity. CoQ10 is especially beneficial for cancer patients taking any chemotherapy drugs associated with heart toxicity (adriamycin, athralines, etc.)
Cardiovascular Disease: CoQ10 is especially indicated for the enhancement of myocardial function by enhancing energy production, improving contractility of the cardiac muscle, and providing potent antioxidant activity, in particular prevention of LDL oxidation. Specific cardiac problems which may benefit from CoQ10 include:
Angina (Kamikawa T, et al. Am J Cardiol 1985;56:247-251)
Arrhythmias (Fujioka T, et al. Tohoku J Exp Med 1983:141(Suppl):453-463.)
Cardiomyopathy (Langsjoen PH, et al. Am J Cardiol 1990:65:521-523; Langsjoen PH, et al. Klin Wochenschr 1988:66:583-590; Langsjoen PH, et al. Drugs Exptl Clin Res 1985;11:577-579)
Congestive heart failure Multiple studies, though not all, have shown the efficacy of CoQ10 in improving numerous cardiac indicators as well as external symptoms.
(Mortensen, SA, et al. Drugs Exptl Clin Res 1985:11:581-593; Baggio E, et al. Clin Invest 1993;71:S145-S149; Morisco C, et al. Clin Invest 1993;71:S134-S136; Khatta M, et al. Ann Intern Med. 2000 Apr 18;132(8):636-40.)
Hypertension 39% of patients with hypertension are deficient in CoQ10, which alone would suggest supplementation, but CoQ10 appears to provide benefits beyond deficiency correction. Improvements are typically not seen until after 4 to 12 weeks of therapy, suggesting that CoQ10 corrects an underlying metabolic imbalance rather than addressing superficial symptoms. Some results indicate that CoQ10 lowers blood pressure by lowering cholesterol and reducing peripheral resistance via its antioxidant properties.
(Digiesi V, et al. Molec Aspects Med 1994;15(Suppl):S257-S263; Langsjoen P, et al. Molec Aspects Med 1994;15(Suppl):S265-S272; Digiesi V, et al. Curr Ther Res 1990;47:841-845.)
Mitral valve prolapse (Oda T, Hamamoto K. Jpn Circ J 1984:48:1387.)
Prevention of adriamycin toxicity (Domae N, et al. Cancer Treat Rep 1981:65:79-91; Karlsson J, et al. In Folkers K, YamamuraY (eds.). 1986; Judy WV, et al. In Folkers, K, Yamamura, Y (eds.). 1984:231-241; Cortes EP, et al. Cancer Treat Rep 1978:62:887-891)
Protection during cardiac surgery (Tanaka J, et al. Ann Thorac Surg 1982:33:145-151.)
Diabetes mellitus: The electron-transport chain is integrally involved in carbohydrate metabolism. CoQ7 at a daily dose of 120 mg for 2-18 weeks reduced fasting blood sugar by at least 30% in 31% of patients.
(Shigeta Y, et al. J Vitaminol 1966;12:293-298.)
• Gastric Ulcers: CoQ10 is protective of the gastric mucosa due to its antioxidant effects. (Kohli, Y, et al. Jpn J Exp Med 1981;51:105-108) Production of protective mucus and rapid cell turnover of gastric mucosa are highly energy-dependent processes.
• Immune Function: CoQ10 enhances phagocytic activity of macrophages and increases granulocyte proliferation. (Mayer, P, Hamberger, H, Drews J. Infection 1980:8:256-261; Saiki I. Tokushima Y. Nishimura K, Azuma I. Int J Vitam Nutr Res 1983:53:312-320; Bliznakov E, Casey A, Premuzic E. Experientia 1970;26:953-954.) Its antioxidant activity helps prevent AIDS-related diseases caused by oxidative stress. (Sugiyama S, et al. Experientia 1980:36:1002-1003.) Blood levels of CoQ10 are lower in AIDS patients and 200 mg per day increased T-helper/suppresser ratios. (Folkers K, et al. Biochem Biophys Res Commun 1988;153:888-896.)
Male Infertility: CoQ7, a CoQ10 analog, at 10 mg/day resulted in significant increases in sperm count and motility.
(Tanimura J. Bull Osaka Med School 1967:12:90-100.)
Muscular Dystrophy: CoQ10 deficiency is found in cardiac and skeletal muscle in animals and humans with hereditary muscular dystrophy. (Liuarru GP, et al. Biochem Biophys Res Commun 1970:41:1306-1313; Folkers K, et al. Proc Natl Acad Sci 1985:82:4513-4516; Folkers K, et al. Proc Natl Acad Sci 1985;82:4513-4516.)
Obesity: Individuals with a family history of obesity have a 50% reduction in thermogenic response to a meal and are often found to have low CoQ10 levels. (van Gaal L, et al. In Folkers K, Yamamura,Y (eds.). 1984, pp. 369-373) CoQ10, being essential for energy production, can be of benefit.
Periodontal Disease: Gingival biopsies yield subnormal tissue levels of CoQ10 in patients with periodontal disease. (Nakamura R, et al. Proc Natl Acad Sci 1 974;7 1:1456-1460; Hansen IL, et al. Res Commun Chem Pathol Pharmacol 1976;14:729-738; Littarru GP, et al. Proc Nati Acad Sci 1971:68:2332-2335; Nakamura R, et al. Int J Vitam Nutr Res 1973:43:84-92.) Supplementation speeds healing after periodontal surgery. (Wilkinson EG, et al. Res Commun Chem Pathol Pharmacol 1976:14:715-719; Wilkinson EG, et al. In Folkers, K, Yamamura, Y (eds.). 1977. pp. 251-265; Wilkinson EG, et al. Res Commun Chem Pathol Pharmacol 1975;12:l 11-124.)
Physical Performance: Supplementation may enhance aerobic capacity and muscle performance, especially in sedentary individuals. (Vanfraecchem JHP, Folkers K. In: Folkers K,Yamamura, Y (eds.). 1981. 235-241.)

» dosage:
Typical dose for most conditions is 30-60 mg twice daily, though many practitioners use doses of 50-100 mg two to three times daily for cardiovascular conditions; some studies on breast cancer treatment used 400 mg daily.

» forms:
• CoQ10 is well-absorbed by oral supplementation as evidenced by significant increases in serum CoQ10 levels after supplementation.
(Gaby AR. Alt Med Rev 1996;1 (1): 11-17.)
• There is some evidence that CoQ10 in oil suspension has the highest bioavailability. (Gaby AR. Alt Med Rev 1996;1 (3):168-175) Bioavailability appears highest in soft-gelatin capsules with Co-Q10 in a base of soybean oil. (Weis M., Mol Aspects Med, 1994;15 (Suppl.), S273-S280.)
Oil-based CoQ10: A study of sixty male cigarette smokers, who were randomly assigned to receive oil-based or granular CoQ10 (90 mg/day) or placebo for two months, confirmed the enhanced bioavailability of Oil-based CoQ10. These researchers found that the oil-based supplement increased the concentration of CoQ10 in plasma by an average of 178%, compared with 168% for the granular preparation. Further, the concentration of CoQ10 in plasma lipoproteins (LDL + VLDL) increased by an average of 160% with the oil-based capsule and by 127% with the granules.
(Kaikkonen J, et al. Free Rad Biol Med 1997;22:1195-1202.)

» side effects/toxicity:
• Occasional reports of nausea, anorexia, or skin eruptions have been reported with supplementation of CoQ10.

» contraindications:
• None known.

» interactions:
• Cholesterol-lowering drugs such as lovastatin and pravastatin inhibit the enzyme 3-hydroxy-3-methyl glutaryl (HMG)-CoA reductase, required for synthesis of cholesterol as well as CoQ10. These drugs may therefore compromise CoQ10 status.
• Beta blockers propranolol and metaprolol inhibit CoQ10-dependent enzymes.
Phenothiazines and tricyclic antidepressants have also been shown to inhibit CoQ10-dependent enzymes.

footnotes

Baggio E, Gandini R, Plancher AC. Passeri M. Carmosino C, et al. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure (interim analysis). Clin Invest 1993;71:5145-S149.

Bargossi AM, et al, Exogenous CoQ10 Supplementation prevents plasma ubiquinone reduction induced by HMG-CoA reductase inhibitors. Mol Aspects Med 15 (Suppl.), S187-S193, 1994

Bliznakov E, Casey A, Premuzic E. Coenzymes Q: stimulants of the phagocytic activity in rats and immune response in mice. Experientia 1 970;26:953-954.

Cortes EP, Gupta M, Chou C, Amin VC, Folkers K. Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treat Rep 1978:62:887-891.

Digiesi V, Cantini F, Brodbeck B. Effect of coenzyme Q10 on essential hypertension. Curr Ther Res 1990;47:841-845.

Digiesi V, Cantini F, Oradel A, Bisi C, Guarino GC, et al. Coenzyme Q10 in essential hypertension. Molec Aspects Med 1994;15(Suppl):S257-S263.

Domae N, Sawada H, Matsuyama E, Konishi T, Uchino H. Cardiomyopathy and other chronic toxic effects induced in rabbits by doxombicin and possible prevention by coenzyme Q10. Cancer Treat Rep 1981:65:79-91.

Folkers K, Langsjoen P, Nara Y, et al. Biochemical deficiencies of coenzyme QIO in HIV infection and exploratory treatment. Biochem Biophys Res Commun 1988;153:888-896.

Folkers K, Wolaniuk J, Simonsen R, et al. Biochemical rationale and the cardiac response of patients with muscle disease to therapy with coenzyme Q10. Proc Natl Acad Sci 1985;82:4513-4516.

Fujioka T, Sakamoto Y, Mimura G. Clinical study of cardiac arrhythmias using a 24-hour continuous electrocardiographic recorder (5th report) - antiarrhythmic action of coenzyme Q10 in diabetics. Tohoku Jap Med 1983:141(Suppl):453-463.

Gaby AR. The role of coenzyme Q10 in clinical medicine: Part I. Alt Med Rev 1996;1(1):11-17.

Gaby AR. The role of coenzyme Q10 in clinical medicine: part II. Cardiovascular disease, hypertension, diabetes mellitus, and infertility. Alt Med Rev 1996;l (3):168-175.

Hamada M., Kazatani Y., Ochi T., et al, Correlation between serum CoQ10 levels and myocardial contractility on hypertensive patients. In: Biomedical and Clinical Aspects of Coenzyme Q, Vol. 4. Folkers K., Yamamura Y., eds. Elsevier Science Publ., Amsterdam, 1984:.263-270.

Hansen IL, Iwamoto Y. Kishi I, Folkers K. Bioenergetics in clinical medicine. IX. Gingival and leucocytic deficiencies of coenzyme Q10 in patients with periodontal disease. Res Commun Chem Pathol Pharmacol 1976;14:729-738.

Ishihara Y, Uchida Y, Kitamura S, Takaku F. Effect of Coenzyme Q10, a quinone derivative, on guinea pig lung and tracheal tissue. Arzneimittelforsch 1985 35 :929-933.

Judy WV, Hall JH, Dugan W, Toth PD, Folkers K. Coenzyme Q10 reduction of adriamycin cardiotoxicity. In: Folkers K, Yamamura Y, (eds.). Biomedical and Clinical Aspects of Coenzvme Q. vol. 4, Elsevier Publ. 1984:231-241.

Kaikkonen J, Nyyssonen K, Porkkala-Sarataho E, Poulsen HE, Metsa-Ketela T, Hayn M, Salonen R, Salonen JT. 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(7):1195-1202.
Abstract: Coenzyme Q10 (Q10) is supposed to be an important endogenous lipid-soluble antioxidant. We studied 60 healthy 46 +/- 7 (mean +/- SD)-year-old smoking men. They were randomized into three groups to receive oil-based or granular Q10 (90 mg/d) or placebo for 2 months. Oil-based capsule elevated Q10 in plasma by 178% and in VLDL+LDL fraction by 160%. The granular preparation increased Q10 in plasma by 168% and in VLDL+LDL by 127%. However, the 2-month Q10 supplementation did not increase the oxidation resistance of VLDL+LDL fraction, as assessed by copper induced VLDL+LDL oxidation, haemin+H(2)O(2)-induced VLDL+LDL oxidation, total antioxidative capacity of LDL, and plasma malondialdehyde measurements. The first and the last dose was used to carry out a 12 h pharmacokinetic study (five subjects per group), which indicated that only a small part of supplemented Q10 was absorbed to the circulation in 12 h and that the absorption varied extensively between subjects. Our results suggest that at least among smoking men, 90 mg of orally supplemented Q10 daily does not increase the oxidation resistance of VLDL+LDL. Bioavailability of both the granular and the oil-based Q10 preparation was similar during the long-term supplementation, but one dose of 30 mg had only a marginal effect on the plasma levels of Q10.

Kamikawa T, Kobayashi A, Yamashita T, Hayashi H, Yamazaki N. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. Am J Cardiol 1985;56:247-251.

Karlsson J, Folkers K, Astrum H, Jansson E, Pernow B, et al. Effect of adriamycin on heart and skeletal muscle coenzyme Q (CoQ10) in man. In Folkers K, Yamamura Y (eds.). Biomedical and Clinical Aspects of Coenzyme Q. volume 5. Elsevier. 1986.

Khatta M, Alexander BS, Krichten CM, Fisher ML, Freudenberger R, Robinson SW, Gottlieb SS. The effect of coenzyme Q10 in patients with congestive heart failure. Ann Intern Med. 2000 Apr 18;132(8):636-640.
Abstract: BACKGROUND: Coenzyme Q10 is commonly used to treat congestive heart failure on the basis of data from several unblinded, subjective studies. Few randomized, blinded, controlled studies have evaluated objective measures of cardiac performance. OBJECTIVE: To determine the effect of coenzyme Q10 on peak oxygen consumption, exercise duration, and ejection fraction. DESIGN: Randomized, double-blind, controlled trial. SETTING: University and Veterans Affairs hospitals. PATIENTS: 55 patients who had congestive heart failure with New York Heart Association class III and IV symptoms, ejection fraction less than 40%, and peak oxygen consumption less than 17.0 mL/kg per minute (or <50% of predicted) during standard therapy were randomly assigned. Forty-six patients completed the study. INTERVENTION: Coenzyme Q10, 200 mg/d, or placebo. MEASUREMENTS: Left ventricular ejection fraction (measured by radionuclide ventriculography) and peak oxygen consumption and exercise duration (measured by a graded exercise evaluation using the Naughton protocol) with continuous metabolic monitoring. RESULTS: Although the mean (+/-SD) serum concentration of coenzyme Q10 increased from 0.95+/-0.62 microg/mL to 2.2+/-1.2 microg/mL in patients who received active treatment, ejection fraction, peak oxygen consumption, and exercise duration remained unchanged in both the coenzyme Q10 and placebo groups. CONCLUSION: Coenzyme Q10 does not affect ejection fraction, peak oxygen consumption, or exercise duration in patients with congestive heart failure receiving standard medical therapy.

Kishi T, Kishi H, Folkers K, Inhibition of cardiac CoQ10-enzymes by clinically used drugs and possible prevention. In: Biomedical and Clinical Aspects of Coenzyme Q, Vol. 1. Folkers K, Yamamura Y, eds. Elsevier/North-Holland Biomedical Press, Amsterdam, 1977, pp. 47-62.

Kohli Y, Suto Y, Kodama T. Effect of hypoxia on acetic acid ulcer of the stomach in rats with or without coenzyme Q10. Jpn J Exp Med 1981;5l:105-108.

Langsjoen PH, Langsjoen PH, Folkers K. Long-term efficacy and safety of coenzyme Q10 therapy for idiopathic dilated cardiomyopathy. Am J Cardiol 1990:65:521-523.

Langsjoen PH, Vadhanavikit S, Folkers K. Effective treatment with coenzyme Q1O of patients with chronic myocardial disease. Drugs Exptl Clin Res 1985;l1:577-579.

Langsjoen P, Langsjoen P, Willis R, Folkers K. Treatment of essential hypertension with coenzyme Q10. Molec Aspects Med 1994;15(Suppl):S265-S272.

Langsjoen PH, Folkers K, Lyson K,. Muratsu K, Lyson I, et al. Effective and safe therapy with coenzyme Q10 for cardiomyopathy. Klin Wochenschr 1988:66:583-590.

Littarru GP, Nakamura R, Ho L, et al. Deficiency of coenzyme Q10 in gingival tissue from patients with periodontal disease. Proc Natl Acad Sci 1971:68:2332-2335.

Liuarru GP, Jones D, Scholler J, Folkers K. Deficiency of coenzyme Q10 in mice having hereditary muscular dystrophy. Biochem Biophys Res Commun 1970:41:1306-1313.

Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in ‘high risk’ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Molec Aspects Med 1994;15(Suppl):S231-S240.

Lockwood K, Moesgaard S, Yamamoto T, Folkers K. Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun 1995:212:172-177.

Mayer P, Hamberger H, Drews J. Differential effects of ubiquinone Q7 and ubiquinone analogs on macrophage activation and experimental infections in granulocytopenic mice. Infection 1980:8:256-261.

Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 in patients with congestive heart failure: a long-term multicenter randomized study. Clin Invest 1993;71:S134-S136.

Mortensen SA, Vadhanavikit S, Baandrup U, Folkers K. Long-term coenzyme Q10 therapy: a major advance in the management of resistant myocardial failure. Drugs Exptl Clin Res 1985:11:581-593.

Nakamura R, Littarru GP, Folkers K, Wilkinson EG. Study of CoQ 10-enzymes in gingiva from patients with periodontal disease and evidence for a deficiency of coenzyme Q10. Proc Natl Acad Sci 1974;71:1456-1460.

Nakamura R,. Littarru GP, Folkers K. Wilkinson EC. Deficiency of coenzyme Q in gingiva of patients with periodontal disease. Int J Vitam Nutr Res 1973:43:84-92.

Oda T, Hamamoto K. Effect of coenzyme Q10 on the stress-induced decrease of cardiac performance in pediatric patients with mitral valve prolapse. Jpn Circ J 1984:48:1387.

Rauchova H, Drahota Z, Lenaz G. Function of coenzyme Q in the cell: some biochemical and physiological properties. Phvsiol Res 1995;44(4):209-216.

Saiki I, Tokushima Y, Nishimura K, Azuma I. Macrophage activation with ubiquinones and their related compounds in mice. Int J Vitam Nutr Res 1983:53:312-320.

Shigeta Y, Izumi K, Abe H. Effect of coenzyme Q7 treatment on blood sugar and ketone bodies of diabetics. J Vitaminol 1966;12:293-298.

Sugiyama S, Kitazawa M,. Ozawa K. Anti-oxidative effect of coenzyme Q10. Experientia 1980:36:1002-1003.

Tanaka J, Tominaga R,Yoshitoshi M, Matsui K, Komori M, Sese, A, et al. Coenzyme Q10: the prophylactic effect on low cardiac output following cardiac valve replacement. Ann Thorac Surg 1982:33:145-151.

Tanimura J. Studies on arginine in human semen. Part III. The influences of several drugs on male infertility. Bull Osaka Med School 1967:12:90-100.

van Gaal L, de Lecuw ID, Vadhanavikit S, Folkers K. Exploratory study of coenzyme Q10 in obesity. In Folkers K, Yamamura Y (eds.). Biomedical and Clinical Aspects of Coenzyme Q, vol. 4, Elsevier Publishers. 1984:369-373.

Vanfraecchem JHP, Folkers K. Coenzyme Q10 and physical performance. In Folkers K,Yamamura, Y (eds.). Biomedical and Clinical Aspects of Coenzyme Q, vol. 3. Elsevier/North-Holland Biomedical Press, Amsterdam, 1981:235-241.

Weber C, Bysted A, Holmer G. Intestinal absorption of coenzyme Q10 administered in a meal or as capsules to healthy subjects. Nutr Res 1997:17:941-945.

Weis M, Mortensent SA, Rassing MR, et al. Bioavailability of four oral coenzyme Q10 formulations in healthy volunteers. Molec Aspects Med 1994:15 (Suppl):S273-S280.

Wilkinson EG, Arnold RM, Folkers K. Treatment of periodontal and other soft tissue diseases of the oral cavity with coenzyme Q. In Folkers, K.Yamamura, Y (eds.). Biomedical and Clinical Aspects of Coenzyme Q, Vol. 1. Elsevier/NorthHolland Biomedical Press. Amsterdam. 1977. pp. 251-265.

Wilkinson EG, Arnold RM, Folkers K. Bioenergetics in clinical medicine. VI. Adjunctive treatment of periodontal disease with coenzyme Q10. Res Commun Chem Pathol Pharmacol 1976:14:715-719.

Wilkinson EG, Arnold RM, Folkers K, et al. Bioenergetics in clinical medicine. II. Adjunctive treatment with coenzyme Q in periodontal therapy. Res Commun Cliem Pathol Pharmacol 1975;12:111-124.