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Coenzyme Q10

Coenzyme Q10

Overview
Courtesy University of Maryland Medical Center
http://www.umm.edu/

Coenzyme Q10 (CoQ10) is a compound found naturally in the energy-producing center of the cell known as the mitochondria. CoQ10 is involved in the making of an important molecule known as ATP. ATP serves as the cell's major energy source and drives a number of biological processes including muscle contraction and the production of protein. CoQ10 also works as an antioxidant.

Antioxidants are substances that scavenge free radicals, damaging compounds in the body that alter cell membranes, tamper with DNA, and even cause cell death. Free radicals occur naturally in the body, but environmental toxins (including ultraviolet light, radiation, cigarette smoking, and air pollution) can also increase the number of these damaging particles. Free radicals are believed to contribute to the aging process as well as the development of a number of health problems including heart disease and cancer. Antioxidants such as CoQ10 can neutralize free radicals and may reduce or even help prevent some of the damage they cause.


 

Uses

CoQ10 boosts energy, enhances the immune system, and acts as an antioxidant. A growing body of research suggests that using coenzyme Q10 supplements alone or in combination with other drug therapies and nutritional supplements may help prevent or treat some of the following conditions:

Heart Disease

Researchers believe that the beneficial effect of CoQ10 in the prevention and treatment of heart disease is due to its ability to improve energy production in cells, inhibit blood clot formation, and act as an antioxidant. One important study, for example, found that people who received daily CoQ10 supplements within 3 days of a heart attack were significantly less likely to experience subsequent heart attacks and chest pain. In addition, these same patients were less likely to die of heart disease than those who did not receive the supplements.

Congestive Heart Failure (CHF)

Levels of CoQ10 are low in people with CHF, a debilitating disease that occurs when the heart is not able to pump blood effectively. This can cause blood to pool in parts of the body such as the lungs and legs. Information from many research studies suggests that CoQ10 supplements help reduce swelling in the legs, enhance breathing by reducing fluid in the lungs, and increase exercise capacity in people with CHF. Not all studies agree, however. As a result, some experts conclude that CoQ10 supplements do not contribute any benefit to the usual conventional treatment for CHF. More conclusive research will help resolve the debate.

High Blood Pressure

Several studies involving small numbers of people suggest that CoQ10 may lower blood pressure. However, it may take 4 to 12 weeks before any beneficial effect is observed. More research with greater numbers of people is needed to assess the value of CoQ10 in the treatment of high blood pressure.

High Cholesterol

Levels of CoQ10 tend to be lower in people with high cholesterol compared to healthy individuals of the same age. In addition, certain cholesterol-lowering drugs called statins (such as atorvastatin, cerivastatin, lovastatin, pravastatin, simvastatin) appear to deplete natural levels of CoQ10 in the body. Taking CoQ10 supplements can correct the deficiency caused by statin medications without affecting the medication's positive effects on cholesterol levels.

Diabetes

CoQ10 supplements may improve heart health and blood sugar and help manage high cholesterol and high blood pressure in individuals with diabetes. (High blood pressure, high cholesterol, and heart disease are all common problems associated with diabetes). Despite some concern that CoQ10 may cause a sudden and dramatic drop in blood sugar (called hypoglycemia), two recent studies of people with diabetes given CoQ10 two times per day showed no hypoglycemic response. The safest bet if you have diabetes is to talk to your doctor or registered dietitian about the possible use of CoQ10.

Heart Damage caused by Chemotherapy

Several studies suggest that CoQ10 may help prevent heart damage caused by certain chemotherapy drugs (namely adriamycin or other athracycline medications). More scientific studies are needed to further evaluate the effectiveness of CoQ10 in preventing heart damage in cancer patients undergoing chemotherapy.

Heart Surgery

Research indicates that introducing CoQ10 prior to heart surgery, including bypass surgery and heart transplantation, can reduce damage caused by free radicals, strengthen heart function, and lower the incidence of irregular heart beat (arrhythmias) during the recovery phase.

Breast Cancer

Studies of women with breast cancer suggest that CoQ10 supplements (in addition to conventional treatment and a nutritional regimen including other antioxidants and essential fatty acids) may shrink tumors, reduce pain associated with the condition, and cause partial remission in some individuals. It is important to recognize that the beneficial effects these women experienced cannot be attributed to CoQ10 alone. Additional antioxidants used in these studies include vitamins C, E, and selenium.

Periodontal (gum) Disease

Gum disease is a widespread problem that is associated with swelling, bleeding, pain, and redness of the gums. Studies have shown that people with gum disease tend to have low levels of CoQ10 in their gums. In a few studies involving small numbers of subjects, CoQ10 supplements caused faster healing and tissue repair. Additional studies are needed to evaluate the effectiveness of CoQ10 when used together with traditional therapy for periodontal disease.

Other

Preliminary studies also suggest that CoQ10 may:

  • Improve immune function in individuals with immune deficiencies (such as AIDS) and chronic infections (such as yeast and other viral infections)
  • Increase sperm motility leading to enhanced fertility
  • Be used as part of the treatment for Alzheimer's disease
  • Reduce damage from stroke
  • Boost athletic performance
  • Enhance physical activity in people with fatigue syndromes
  • Improve exercise tolerance in individuals with muscular dystrophy

Research in all of these areas is underway to determine whether CoQ10 can be safety and effectively used in people with these health problems.


 

Dietary Sources

Primary dietary sources of CoQ10 include oily fish, organ meats such as liver, and whole grains. Most individuals obtain sufficient amounts of CoQ10 through a balanced diet, but supplementation may be useful for individuals with particular health conditions (see Uses section) or those taking certain medications (see Interactions section).


 

Available Forms

Coenzyme Q10 is available as a supplement in several forms, including softgel capsules, oral spray, hardshell capsules, and tablets.


 

How to Take It

Pediatric

There are no known scientific reports on the pediatric use of CoQ10. Therefore, use of CoQ10 supplements is not currently recommended for children.

Adult

The general recommended dose for CoQ10 supplementation is 30 to 60 mg daily. Higher doses have been used in studies and may be recommended for the following conditions:

  • Congestive heart failure: 50 to 150 mg a day
  • High blood pressure: 50 to 150 mg a day
  • To enhance athletic performance: 60 mg a day for 4 to 8 weeks
  • Heart attack: 120 mg a day for 28 days after the heart attack
  • Breast cancer: 400 mg per day for potential prevention and treatment

Coenzyme Q10 is fat-soluble so should be taken with a meal containing fat for optimal absorption.


 

Precautions

Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable healthcare provider.

Coenzyme Q10 appears to be generally safe with no significant side effects, except occasional stomach upset. However, the safety of CoQ10 supplementation during pregnancy and breastfeeding is unknown and, therefore, should not be used during that time until more information is available.


 

Possible Interactions

If you are currently being treated with any of the following medications, you should not use CoQ10 without first talking to your healthcare provider.

Daunorubicin and Doxorubicin
Coenzyme Q10 may help to reduce the toxic effects on the heart caused by daunorubicin and doxorubicin, two chemotherapy medications that are commonly used to treat a variety of cancers.

Blood Pressure Medications
In a study of individuals taking blood pressure medications (including diltiazem, metoprolol, enalapril, and nitrate), CoQ10 supplementation allowed the individuals to take lower dosages of these drugs. This suggests that CoQ10 may enhance the effectiveness of certain blood pressure medications, but more research is needed to verify these results.

Warfarin
There have been reports that coenzyme Q10 may decrease the effectiveness of blood-thinning medications such as warfarin, leading to the need for increased doses. Therefore, given that this medication must be monitored very closely for maintenance of appropriate levels and steady blood thinning, CoQ10 should only be used with warfarin under careful supervision by your healthcare provider.

Timolol
CoQ10 supplementation may reduce the heart-related side effects of timolol drops, a beta-blocker medication used to treat glaucoma, without decreasing the effectiveness of the medication.

Other
Medications that can lower the levels of coenzyme Q10 in the body include statins for cholesterol (atorvastatin, cerivastatin, lovastatin, pravastatin, simvastatin), fibric acid derivatives for cholesterol (specifically, gemfibrozil), beta-blockers for high blood pressure (such as atenolol, labetolol, metoprolol, and propranolol), and tricyclic antidepressant medications (including amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, and trimipramine).


 

Supporting Research

Aberg F, Appelkvist EL, Broijersen A, et al. Gemfibrozil-induced decrease in serum ubiquinone and alpha- and gamma-tocopherol levels in men with combined hyperlipidaemia. Eur J Clin Invest . 1998;28:235-242.

Al-Hasso. Coenzyme Q10: a review. Hosp Pharm . 2001;36(1):51-66.

Alleva R, Scaraarmucci A, Mantera F, Bompandre S, Leoni L, Linarro GP. The protective role of ubiquinol?10 against formation of lipid hydroperoxdes in human seminal fluids. Mol Asp Med . 1997;18:221-228.

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):s287-294.

Chello M, Mastroroberto P, Romano R, et al. Protection by coenzyme Q10 from myocardial reperfusion injury during coronary artery bypass grafting. Ann Thorac Surg . 1994;58(5):1427-1432.

Chopra RK, Goldman R, Sinatra ST, Bhagavan HN. Relative bioavailability of coenzyme Q10 formulations in human subjects. Int J Vitam Nutr Res . 1998;68:109-113.

de Bustos F, Molina JA, Jimenez-Jimenz FJ, Garcia-Redondo A, Gomez-Escalonilla C, Porta-Etessam J, et al. Serum levels of coenzyme Q10 in patients with Alzheimer's disease. J Neural Transm . 2000;107(2):233-239.

Eriksson JG. The effects of coenzyme Q10 administration on metabolic control in patients with type 2 diabetes mellitus. Biofactors . 1999;9(2-4):315-318.

Folkers K, Langsjoen P, Nara Y, et al. Biochemical deficiencies of coenzyme Q10 in HIV infection and exploratory treatment. Biochem Biophys Res Commun . 1988;153:888-896.

Hanioka T, Tanaka M, Ojima M, Shizukuishi S, Folkers K. Effect of topical application of coenzyme Q10 on adult periodontitis. Mol Aspects Med. 1994;15 Suppl:s241-248.

Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health-System Pharm . 2000;57(13):1221-1227.

Henriksen J, Andersen CB, Hother-Nielsen O, Vaag A, Mortensen SA, Beck-Nielsen H. Impact of ubiquinone (coenzyme Q10) treatment on glycaemic control, insulin requirement and well-being in patients with type 1 diabetes mellitus. Diabet Med . 1999; 16:312-8.

Human JA, Ubbink JB, Jerling JJ, et al. The effect of simvastatin on the plasma antioxidant concentrations in patients with hypercholesterolemia. Clin Chim Acta . 1997;263(1):67-77.

Iarussi D, Auricchio U, Agretto A, et al. Protective effect of coenzyme Q on anthracylines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-hodgkin lymphoma. Molec Aspects Med . 1994;15(Suppl):S207-S212.

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.

Judy WV, Hall JH, Dugan W, et al. Coenzyme Q10 reduction of adriamycin cardiotoxicity. In: Folkes K, Yamamura Y, Eds. Biomedical and clinical aspects of coenzyme Q10 , Vol. 4. Amsterdam: Elsevier. 1984:231-241.

Kendler BS. Recent nutritional approaches to prevention and therpy of cardiovascular disease. Prog Cardiovasc Nurs . 1997;12(3):3-23.

Khatta M, Alexander BS, Krichten CM, Fisher ML, Freudenberger R, Robinson SW et al. The effect of conenzyme Q10 in patients with congestive heart failure. Ann Int Med . 2000;132(8):636-640.

Landbo C, Almdal TP. Drug interaction between warfarin and coenzyme Q10. Ugeskrift for Laeger . 1998;160(22):3226-3227.

Langsjoen P, Langsjoen A. Overview of the use of CoQ10 in cardiovascular disease. BioFactors . 1999;9:273-284.

Langsjoen P, Langsjoen A, Willis R, Folkers K. Treatment of Essential Hypertension with Coenzyme Q10. Molec Aspects Med . 1994;15:s265-s272.

Lewin A, Loron M. The effect of coenzyme Q10 on sperm mobility and function. Mol Asp Med . 1997;18:213-219.

Lockwood K, Moesgaard S, Folkers K. Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Commun . 1994;199(3):1504-1508.

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. Mol AspMed . 1994;15 Suppl:s231-s240.

Lockwood K, Moesgaard S, Yamamoto T, Folkers K. Progress in therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun. 1995;212(1):172-177.

Marz W, Wieland H. HMG-CoA reducatse inhibition: anti-inflammatory effects beyond lipid lowering. Herz . 2000;25(6):117-25.

Matthews RT, Yang L, Browne S, Baik M, Beal MF. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci USA. July 21, 1998; 95:8892-8897.

McCarty MF. Coenzyme Q versus hypertension: does CoQ decrease endothelial superoxide generation? Med Hypotheses. 1999;53:300-304.

McCarty MF. Toward practical prevention of type 2 diabetes. Med Hypotheses. 2000;54(5):786-793.

Miyake Y, Shouza A, Nishikawa M, Yonemoto T, Shimizu H, Omoto S, Hayakawa T, Inada M. Effect of treatment with 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitors on serum coenzyme Q10 in diabetic patients. Arzneimittelforschung . 1999;49(4):324-329.

Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med . 1997;18Suppl:S137-S144.

Musumeci O, Naini A, Slonim AE, Skavin N, Hadjigeorgiou GL, Krawiecki N, et al. Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurol . 2001;56(7):849-855.

Niibori K, Yokoyama H, Crestanello JA, Whitman GJ. Acute administration of liposomal coenzyme Q10 increases myocardial tissue levels and improves tolerance to ischemia reperfusion injury. J Surg Res . 1998;79:141-145.

Ostrowski RP. Effect of coenzyme Q(10) on biochemical and morphological changes in experimental ischemia in the rat brain. Brain Res Bull . 2000;53(4):399-407.

Ott BR, Owens NJ. Complementary and alternative medicines for Alzheimer's disease. J Geriatr Psychiatry Neurol . 1998;11:163-173.

Overvad K, Diamant B, Holm L, Holmer G, Mortensen SA, Stender S. Review coenzyme Q10 in health and disease. Eur J Clin Nut . 1999;53:764-770.

Raitakari OT, McCredie RJ, Witting P, Griffiths KA, Letter J, Sullivan D, Stocker R, Celermajer DS. Coenzyme Q improves LDL resistance to ex vivo oxidation but does not enhance endothelial function in hypercholesterolemic young adults. Free Radic Biol Med . 2000;28(7):1100-1105.

Serebruany VL, Ordonez JV, Herzog WR, et al. Dietary coenzyme Q10 supplementation alters platelet size and inhibits human vitronectin (CD51/CD61) receptor expression . J Cardiovasc Pharmacol. 1997;29:16-22.

Shils ME, Olson JA, Shike M, Ross AC. Modern Nutrition in Health and Disease . 9th ed. Baltimore, Md: Williams & Wilkins; 1999:90-92: 1377-1378.

Shinozawa S, Kawasaki H, Gomita Y. [Effect of biological membrane stabilizing drugs (coenzyme Q10, dextran sulfate and reduced glutathione) on adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice]. Gan To Kagaku Ryoho . 1996;23(1):93-98.

Sinclair S. Male infertility: nutritional and environmental considerations. Alt Med Rev . 2000;5(1):28-37.

Singh RB, Niaz MA, Rastogi SS, Shukla PK, Thakur AS. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens . 1999;13(3):203-208.

Singh RB, Wander GS, Rastogi A, et al. Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc Drugs Ther. 1998;12:347-353.

Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet . 1994;344:1372-1373.

Takahashi N, Iwasaka T, Sugiura T, et al. Effect of coenzyme Q10 on hemodynamic response to ocular timolol. J Cardiovasc Pharmacol . 1989;14:462-468.

Torkos S. Drug-nutrient interactions: A focus on cholesterol-lowering agents. Int J Integrative Med . 2000;2(3):9-13.

Tsukahara Y, Wakatsuki A, Okatani Y. Antioxidant role of endogenaous coenzyme Q against the iscemic and reperfusion-induced lipid peroxidation in fetal rat brain. Acta Obstet Gynecol Scand . 1999;78(8):669-674.

Werbach M. Foundations of Nutritional Medicine . Tarzana, Calif: Third Line Press, Inc.; 1997:209.

Wilkinson EG, Arnold RM, Folkers K. Treatment of periodontal and other soft tissue diseases in the oral cavity with coenzyme Q10. In: Folker K, Yamamura Y, eds. Biomedical and Clinical Aspects of Coenzyme Q10 , Vol 1. Elsevier/North-Holland Biomedical Press;Amsterdam, 1977:251-265.

Witte KK, Clark AL, Cleland JG. Chronic heart failure and micronutrients. J Am Coll Cardiol . 2001;37(7):1765-1774.

Zhou Q, Chan E. Accuracy of repeated blood sampling in rats: A new technique applied in pharmacokinetic/pharmacodynamic studies of the interaction between warfarin and Co-enzyme Q10. J Pharmacol Toxicol Methods . 1998;40(4):191-199. 

Myocardial preservation by therapy with coenzyme Q10 during heart surgery

USA CLIN. INVEST. SUPPL. (Germany), 1993, 71/8 (S 155-S 161)

Coenzyme Q10 (CoQ10) is a natural and essential cofactor in the heart. It is the primary redox coupler in the respiratory chain, a potent free radical scavenger, and a superoxide inhibitor. In this study the myocardial protective effects of CoQ10 were determined in high-risk (n = 10) patients during heart surgery compared to that found in placebo controls (n = 10). In both groups, there was a blood CoQ10 deficiency (<0.6 microg/ml), low cardiac index (CI < 2.4 l/m2 per minute), and low left ventricular ejection fraction (LVEF <35%) before treatment. CoQ10 (100 mg per day) was given orally for 14 days before and 30 days after surgery. Presurgical CoQ10 treatment significantly (P < 0.01) improved blood and myocardial CoQ10 and myocardial ATP compared to that found in the control group. Cardiac functions (CI and LVEF) were improved but not significantly. After cardiac cooling, rewarming, and reperfusion; blood and tissue CoQ10 and tissue ATP levels were maintained in the normal ranges in the CoQ10 patients. Cardiac pumping (CI) and LVEF were significantly (P < 0.01) improved. The recovery course was short (3-5 days) and uncomplicated. In the control group blood and tissue CoQ10, tissue ATP levels, and cardiac functions were depressed after surgery. The recovery course was long (15-30 days) and complicated. Positive relationships between blood and myocardial CoQ10, myocardial ATP, cardiac function, and the postoperative recovery time and course found in both study groups show the therapeutic benefits of CoQ10 in preserving the myocardium during heart surgery. CoQ10 treatment is especially indicated in high-risk cardiac surgery patients who have a natural or clinically induced CoQ10 deficiency.


Effect of CoQ10 on myocardial ischemia/reperfusion injury in the isolated rat heart

Journal of the Japanese Association for Thoracic Surgery (Japan), 1995, 43/4 (466-472)

It has been reported to CoQ10, ubiquinone may have a protective effect on the mitochrondrial injury induced by myocardial ischemia and reperfusion during open heart surgery. The purpose of this study was to investigate whether CoQ10 may enhance myocardial protection when given before ischemia, during ischemia or during reperfusion in the isolated working rat heart. Hearts (n = 6 - 9/group) from male Wistar rats were aerobically (37degreeC) perfused (20 min) with bicarbonate buffer. In the first series of studies, this was followed by a 3 min infusion of St. Thomas' Hospital cardioplegic solution containing various concentrations of CoQ10. Hearts were then subjected to 39 min of normothermic (37degreeC) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). The percent recovery of aortic flow (% AF) was 50.5 plus or minus 3.3% in the CoQ10, free controls versus 55.9 plus or minus 4.44, 62.1 plus or minus 5.4, 71.4 plus or minus 3.1% ((*) p < 0.05) in the 29, 44 and 58 micromol/L CoQ10 groups, respectively. Creatine kinase (CK) leakage during Langendorff reperfusion had a tendency to decrease in the 58 micromol/L group. In the second series of studies, 3 min of cardioplegia with 0 or 58 micromol/L of CoQ10 and 20 min working reperfusion. % AF was 53.2 plus or minus 2.7 and 39.2 plus or minus 7.1% in the 0 and 58 micromol/L CoQ10 groups, respectively. CK leakage had a tendency to increase in the 58 micromol/L group. In the third series of studies, 7.5 micromol of CoQ10 was administered over 10 min prior to a 3 min infusion of St. Thomas' Hospital cardioplegic solution. Hearts were then subjected to 36 min of normothermic (37degreeC) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). %AF was 43.8 plus or minus 1.8 and 47.5 plus or minus leakage between the two groups. Thus CoQ10 when given during ischemia, enhanced myocardial protection. This might indicate that CoQ10 could play an important role in the protective effect on mitochondrial dysfunction during myocardial ischemia.


Measurement of the ratio between the reduced and oxidized forms of coenzyme Q10 in human plasma as a possible marker of oxidative stress.

J Lipid Res (UNITED STATES) Jan 1996, 37 (1) p67-75

It has been postulated that lipid peroxidation plays a crucial role in the pathogenesis of atherosclerosis. As CoQ10H2 (reduced form of coenzyme Q10) is easily oxidized to CoQ10 (oxidized form of coenzyme Q10), it has been proposed that the CoQ10H2/CoQ10 ratio may be used as a possible marker of in vivo oxidative stress. However, sample preparation has an important effect on the redox status of coenzyme Q10 due to the extreme sensitivity of CoQ10H2 towards oxidation. We now report a rapid, simple isocratic HPLC procedure for the determination of CoQ10H2 and CoQ10 in plasma isopropanol extracts, and we used this method to investigate conditions by which the CoQ10H2/CoQ10 ratio can be reliably measured. Our results indicate that CoQ10H2 is unstable in whole blood, plasma, and isopropanol extracts; subsequently the CoQ10H2/CoQ10 ratio changes considerably soon after a blood sample has been obtained. The time period since blood sampling and HPLC analysis, as well as the sample pretreatment procedure, are two factors that have a profound effect on the pre-analytical variation in the determination of the CoQ10H2/CoQ10 ratio. If these two factors are properly controlled, the CoQ10H2/CoQ10 ratio may be a sensitive and practical way to measure in vivo oxidative stress. Furthermore, this indicator is independent from plasma total cholesterol concentrations, implying that groups who differ with respect to cholesterol levels may be compared directly.


The role of free radicals in disease

Australian and New Zealand Journal of Ophthalmology (Australia), 1995, 23/1

Evidence is accumulating that most of the degenerative diseases that afflict humanity have their origin in deleterious free radical reactions. These diseases include atherosclerosis, cancer, inflammatory joint disease, asthma, diabetes, senile dementia, and degenerative eye disease. The process of biological ageing might also have a free radical basis. Most free radical damage to cells involves oxygen free radicals or, more generally, activated oxygen species (AOS) which include non-radical species such as singlet oxygen and hydrogen peroxide as well as free radicals. The AOS can damage genetic material, cause lipid peroxidation in cell membranes, and inactivate membrane-bound enzymes. Humans are well endowed with antioxidant defences against AOS; these antioxidants, or free radical scavengers, include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), beta-carotene, coenzyme Q10, enzymes such as catalase and superoxide dismutase, and trace elements including selenium and zinc. The eye is an organ with intense AOS activity, and it requires high levels of antioxidants to protect its unsaturated fatty acids. The human species is not genetically adapted to survive past middle age, and it appears that antioxidant supplementation of our diet is needed to ensure a more healthy elderly population.


Coenzyme Q10 and coronary artery disease

CLIN. INVEST. SUPPL. (Germany), 1993, 71/8

It has been postulated that oxidatively modified low- density lipoprotein (LDL) contributes to the genesis of atherosclerosis. Ubiquinone has been suggested to be an important physiological lipid-soluble antioxidant and is found in LDL fractions in the blood. We measured plasma level of ubiquinone using high-performance liquid chromatography and plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in 245 normal subjects (186 males, 59 females) and in 104 patients (55 males, 49 females) who had coronary artery disease not receiving pravastatin and 29 patients (12 males, 17 females) receiving pravastatin. In the normal subjects, the plasma ubiquinone levels did not vary with age. In the patient groups, the plasma total cholesterol and LDL levels were higher and the plasma ubiquinone level lower than in the normal subject group. The LDL/ubiquinone ratio was higher in the patient groups. We found that ubiquinone level, either alone or when expressed in relation to LDL levels, was significantly lower in the patient groups compared with the normal subject group. The 3-hydroxy-3-methylglutaryl coenzyme A (HMC CoA) reductase inhibitor is thought to prevent atherosclerosis, however, it also inhibits ubiquinone production. The present study revealed that HMG CoA reductase inhibitor decreased plasma cholesterol level, and that it did not improve either the ubiquinone level or the LDL/ubiquinone ratio. From these results, the LDL/ubiquinone ratio is likely to be a risk factor for atherogenesis, and administration of ubiquinone to patients at risk might be needed.


Isoprenoids (coQ10) in aging and neurodegeneration.

Neurochem Int (ENGLAND) Jul 1994, 25 (1) p35-8

During aging the human brain shows a progressive increase in levels of dolichol, a reduction in levels of ubiquinone, but relatively unchanged concentrations of cholesterol and dolichyl phosphate. In a neurodegenerative disease, Alzheimer's disease, the situation is reversed with decreased levels of dolichol and increased levels of ubiquinone. The concentrations of dolichyl phosphate are also increased, while cholesterol remains unchanged. This study shows that the isoprenoid changes in Alzheimer's disease differ from those occurring during normal aging and that this disease cannot, therefore, be regarded as a result of premature aging. The increase in the sugar carrier dolichyl phosphate may reflect an increased rate of glycosylation in the diseased brain and the increase in the endogenous anti-oxidant ubiquinone an attempt to protect the brain from oxidative stress, for instance induced by lipid peroxidation.


Muscle biopsy in Alzheimer's disease: Morphological and biochemical findings

CLIN. NEUROPATHOL. (Germany), 1991, 10/4 (171-176)

Recent evidences of a predisposing genetic factor associated with Alzheimer's disease (DAT) suggests that important alterations may be expressed in tissues other than the brain. We present morphological and biochemical studies on muscle obtained from ten patients with Alzheimer's disease and coeval controls. Muscle biopsy examination showed an increased subsarcolemmal mitochondrial oxidative activity in three patients. The biochemical studies showed an increased oxidative enzyme activity only in the DAT group. The CoQ10 level, studied so far in three DAT patients, was greatly reduced (similar50%) compared with controls. Possible new peripheral markers in Alzheimer's disease will be discussed.


Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy

Biochemical and Biophysical Research Communications (USA), 1996, 224/2 (358-361)

In the human, coenzyme Q10 (vitamin Q10) is biosynthesized from tyrosine through a cascade of eight aromatic precursors. These precursors indispensably require eight vitamins, which are tetrahydrobiopterin, vitamins B6 C, B2, B12, folic acid, niacin, and pantothenic acid as their coenzymes. Three of these eight vitamins (the coenzyme B6 and the coenzymes niacin and folic acid) are indispensable in the biosynthesis of the four bases (thymidine, guanine, adenine, and cytosine) of DNA. One or more of the three vitamins required for DNA are known to cause abnormal pairing of the four bases, which can then result in mutations and the diversity of cancer. The coenzyme B6 required for the conversion of tyrosine to p- hydroxybenzoic acid, is the first coenzyme required in the cascade of precursors. A deficiency of the coenzyme B6 can cause dysfunctions, prior to the formation of vitamin Q10 to DNA. Former data on blood levels of Q10 and new data herein on blood levels of B6, measured as EDTA, in cancer patients established deficiencies of Q10 and B6 in cancer. This complete biochemistry relating to biosyntheses of Q10 and the DNA bases is a rationale for the therapy of cancer with Q10 and other entities in this biochemistry.


Natural products and their derivatives as cancer chemopreventive agents

Progress in Drug Research (Switzerland), 1997, 48/- (147- 171)

This review summarizes currently available data on the chemopreventive efficacies, proposed mechanisms of action and relationships between activities and structures of natural products like vitamin D, calcium, dehydroepidandrosterone, coenzyme Q10, celery seed oil, parsley leaf oil, sulforaphane, isoflavonoids, lignans, protease inhibitors, tea polyphenols, curcumin, and polysaccharides from Acanthopanax genus.


Thesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy

Biochemical and Biophysical Research Communications (USA), 1996, 224/2 (358-361)

In the human, coenzyme Q10 (vitamin Q10) is biosynthesized from tyrosine through a cascade of eight aromatic precursors. These precursors indispensably require eight vitamins, which are tetrahydrobiopterin, vitamins B6 C, B2, B12, folic acid, niacin, and pantothenic acid as their coenzymes. Three of these eight vitamins (the coenzyme B6 and the coenzymes niacin and folic acid) are indispensable in the biosynthesis of the four bases (thymidine, guanine, adenine, and cytosine) of DNA. One or more of the three vitamins required for DNA are known to cause abnormal pairing of the four bases, which can then result in mutations and the diversity of cancer. The coenzyme B6 required for the conversion of tyrosine to p- hydroxybenzoic acid, is the first coenzyme required in the cascade of precursors. A deficiency of the coenzyme B6 can cause dysfunctions, prior to the formation of vitamin Q10 to DNA. Former data on blood levels of Q10 and new data herein on blood levels of B6, measured as EDTA, in cancer patients established deficiencies of Q10 and B6 in cancer. This complete biochemistry relating to biosyntheses of Q10 and the DNA bases is a rationale for the therapy of cancer with Q10 and other entities in this biochemistry.


The effect of coenzyme Q10 on infarct size in a rabbit model of ischemia/reperfusion.

Birnbaum Y; Hale SL; Kloner RA. Heart Institute, Good Samaritan Hospital, Los Angeles, CA 90017, USA. Cardiovasc Res (NETHERLANDS) Nov 1996, 32 (5) p861-8

OBJECTIVE: Coenzyme Q10 has been found to enhance recovery of function after reperfusion in numerous experimental acute ischemia-reperfusion models. We assessed whether coenzyme Q10, administered intravenously either during or 1 h before ischemia, can limit infarct size in the rabbit.

METHODS: Anesthetized open-chest rabbits were subjected to 30 min of coronary artery occlusion and 4 h of reperfusion. In Protocol 1, 12 min after beginning of ischemia rabbits were randomized to intravenous infusion of 30 mg coenzyme Q10 (Eisai Co., Japan) (n = 10) or vehicle (n = 10). In Protocol 2, rabbits were randomized to 30 mg coenzyme Q10 (n = 6) or vehicle (n = 6) treatment 60 min before ischemia. Ischemic zone at risk (IZ) was assessed by blue dye and necrotic zone (NZ) by tetrazolium staining.

RESULTS: In both protocols, coenzyme Q10 did not alter heart rate, mean blood pressure, or regional myocardial blood flows in either the ischemic or non-ischemic zones during ischemia or reperfusion. No difference was found in IZ (as fraction of LV weight) (Protocol 1: 0.24 +/- 0.02 vs. 0.25 +/- 0.02; Protocol 2: 0.28 +/- 0.02 vs. 0.28 +/- 0.03, in the control vs. coenzyme Q10 groups, respectively). The NZ/IZ ratio was comparable between the groups in both protocols (Protocol 1: 0.22 +/- 0.04 vs. 0.26 +/- 0.04; Protocol 2: 0.21 +/- 0.06 vs. 0.30 +/- 0.06, in the control vs. coenzyme Q10 groups, respectively).

CONCLUSIONS: Coenzyme Q10, administered acutely either during or 60 min before myocardial ischemia, does not attenuate infarct size in the rabbit.


Protection by coenzyme Q10 of tissue reperfusion injury during abdominal aortic cross-clamping.

Chello M; Mastroroberto P; Romano R; Castaldo P; Bevacqua E; Marchese AR. Medical School of Catanzaro, Italy. J Cardiovasc Surg (Torino) (ITALY) Jun 1996, 37 (3) p229-35

PURPOSE: To evaluate the effect of coenzyme Q10 in reducing the skeletal muscle reperfusion injury following clamping and declamping the abdominal aorta.

METHODS: 30 patients undergoing elective vascular surgery for abdominal aortic aneurysm or obstructive aorto-iliac disease were randomly divided into two groups: patients in group I were treated with coenzyme Q10 (150 mg/day) for seven days before operation, and those in group II received a placebo. We studied the hemodynamic profile in each patient during clamping and declamping of the abdominal aorta. The plasma concentrations of thiobarbituric acid reactive substances (malondialdhehyde), conjugated dienes, creatine kinase and lactate dehydrogenase were measured in samples from both arterial and inferior vena cava sites. Serial sampling was performed after induction of anesthesia, 5 and 30 minutes after abdominal aortic cross clamping, 5 and 30 minutes after aortic cross-clamp removal.

RESULTS: The concentrations of malondialdehyde, conjugated dienes, creatine kinase and lactate dehydrogenase in patients who received CoQ10 were significantly lower than in the placebo group. Decrease of plasma malondialdehyde concentrations correlated positively (p < 0.01) with decrease of both creatine kinase and lactate dehydrogenase release in samples from the inferior vena cava. The hemodynamic profile during clamping and declamping the abdominal aorta was similar in both groups.

CONCLUSIONS: Our findings suggest that pre-treatment with coenzyme Q10 may play a protective role during routine vascular procedures requiring abdominal aortic cross clamping by attenuating the degree of peroxidative damage.


Isoprenoid (coQ10) biosynthesis in multiple sclerosis.

Acta Neurol Scand (DENMARK) Sep 1985, 72 (3) p328-35

Recently discovered metabolites in urine have suggested a defect of isoprenoid metabolism in multiple sclerosis. Lymphocyte HMG-CoA reductase was found unaffected however, and so was lymphocyte biosynthesis of geraniol, farnesol and squalene from mevalonolactone. The level of dolichol in white matter of an MS brain was similar to that of a control sample. Serum ubiquinone, on the other hand, was decreased in multiple sclerosis. Ubiquinone in serum was both age-dependent and related to serum cholesterol. Active as well as stable MS displayed a decreased level of serum ubiquinone, and a reduced ubiquinone-cholesterol ratio. These results are compatible with a deficient ubiquinone biosynthesis in multiple sclerosis.


Two successful double-blind trials with coenzyme Q10 (vitamin Q10) on muscular dystrophies and neurogenic atrophies.

Biochim Biophys Acta (NETHERLANDS) May 24 1995

Coenzyme Q10 (vitamin Q10) is biosynthesized in the human body and is functional in bioenergetics, anti-oxidation reactions, and in growth control, etc. It is indispensable to health and survival. The first double-blind trial was with twelve patients, ranging from 7-69 years of age, having diseases including the Duchenne, Becker, and the limb-girdle dystrophies, myotonic dystrophy. Charcot-Marie- Tooth disease, and the Welander disease. The control coenzyme Q10 (CoQ10) blood level was low and ranged from 0.5-0.84 microgram/ml. They were treated for three months with 100 mg daily of CoQ10 and a matching placebo. The second double-blind trial was similar with fifteen patients having the same categories of disease. Since cardiac disease is established to be associated with these muscle diseases, cardiac function was blindly monitored, and not one mistake was made in assigning CoQ10 and placebo to the patients in both trials. Definitely improved physical performance was recorded. In retrospect, a dosage of 100 mg was too low although effective and safe. Patients suffering from these muscle dystrophies and the like, should be treated with vitamin Q10 indefinitely.


Biochemical rationale and the cardiac response of patients with muscle disease to therapy with coenzyme Q10.

Proc Natl Acad Sci U S A (UNITED STATES) Jul 1985

Cardiac disease is commonly associated with virtually every form of muscular dystrophy and myopathy. A double- blind and open crossover trial on the oral administration of coenzyme Q10 (CoQ10) to 12 patients with progressive muscular dystrophies and neurogenic atrophies was conducted. These diseases included the Duchenne, Becker, and limb-girdle dystrophies, myotonic dystrophy, Charcot- Marie-Tooth disease, and Welander disease. The impaired cardiac function was noninvasively and extensively monitored by impedance cardiography. Solely by significant changeor no change in stroke volume and cardiac output, all 8 patients on blind CoQ10 and all 4 on blind placebo were correctly assigned (P less than 0.003). After the limited 3-month trial, improved physical well-being was observed for 4/8 treated patients and for 0/4 placebo patients; of the latter, 3/4 improved on CoQ10; 2/8 patients resigned before crossover; 5/6 on CoQ10 in crossover maintained improved cardiac function; 1/6 crossed over from CoQ10 to placebo relapsed. The rationale of this trial was based on known mitochondrial myopathies, which involve respiratory enzymes, the known presence of CoQ10 in respiration, and prior clinical data on CoQ10 and dystrophy. These results indicate that the impaired myocardial function of such patients with muscular disease may have some association with impaired function of skeletal muscle, both of which may be improved by CoQ10 therapy. The cardiac improvement was definitely positive. The improvement in well-being was subjective, but probably real. Likely, CoQ10 does not alter genetic defects but can benefit the sequelae of mitochondrial impairment from such defects. CoQ10 is the only known substance that offers a safe and improvedquality of life for such patients having muscle disease, and it is based on intrinsic bioenergetics.


[Some indices of energy metabolism in the tissues of mice with progressive muscular dystrophy under the action of ubiquinone]

Vopr Med Khim (USSR) May 1974, 20 (3) p276-84

Coenzyme Q10 (vitamin Q10) is biosynthesized in the human body and is functional in bioenergetics, anti-oxidation reactions, and in growth control, etc. It is indispensable to health and survival. The first double-blind trial was with twelve patients, ranging from 7-69 years of age, having diseases including the Duchenne, Becker, and the limb-girdle dystrophies, myotonic dystrophy. Charcot-Marie- Tooth disease, and the Welander disease. The control coenzyme Q10 (CoQ10) blood level was low and ranged from 0.5-0.84 microgram/ml. They were treated for three months with 100 mg daily of CoQ10 and a matching placebo. The second double-blind trial was similar with fifteen patients having the same categories of disease. Since cardiac disease is established to be associated with these muscle diseases, cardiac function was blindly monitored, and not one mistake was made in assigning CoQ10 and placebo to the patients in both trials. Definitely improved physical performance was recorded. In retrospect, a dosage of 100 mg was too low although effective and safe. Patients suffering from these muscle dystrophies and the like, should be treated with vitamin Q10 indefinitely.


The activities of coenzyme Q10 and vitamin B6 for immune responses.

Biochem Biophys Res Commun (UNITED STATES) May 28 1993, 193 (1)

Coenzyme Q10 (CoQ10) and vitamin B6 (pyridoxine) have been administered together and separately to three groups of human subjects. The blood levels of CoQ10 increased (p < 0.001) when CoQ10 and pyridoxine were administered together and when CoQ10 was given alone. The blood levels of IgG increased when CoQ10 and pyridoxine were administered together (p < 0.01) and when CoQ10 was administered alone (p < 0.05). The blood levels of T4- lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.01) and separately (p < 0.001). The ratio of T4/T8 lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.001) and separately (p < 0.05). These increases in IgG and T4-lymphocytes with CoQ10 and vitamin B6 are clinically important for trials on AIDS, other infectious diseases, and on cancer.


Research on coenzyme Q10 in clinical medicine and in immunomodulation.

Drugs Exp Clin Res (SWITZERLAND) 1985, 11 (8) p539-45

Coenzyme Q10 (CoQ10) is a redox component in the respiratory chain. CoQ10 is necessary for human life to exist; and a deficiency can be contributory to ill health and disease. A deficiency of CoQ10 in myocardial disease has been found and controlled therapeutic trials haveestablished CoQ10 as a major advance in the therapy of resistant myocardial failure. The cardiotoxicity of adriamycin, used in treatment modalities of cancer, is significantly reduced by CoQ10, apparently because the side-effects of adriamycin include inhibition of mitochondrial CoQ10 enzymes. Models of the immune system including phagocytic rate, circulating antibody level, neoplasia, viral and parasitic infections were used to demonstrate that CoQ10 is an immunomodulating agent. It was concluded that CoQ10, at the mitochondrial level, is essential for the optimal function of the immune system.


A modified determination of coenzyme Q10 in human blood and CoQ10 blood levels in diverse patients with allergies.

Biofactors (ENGLAND) Dec 1988, 1 (4) p303-6

Two situations required a modified determination of coenzyme Q10 (CoQ10) in human blood and organ tissue. Blood from patients with AIDS and cancer raised apprehensions about safety to an analyst, and the number of specimens for analysis is increasing enormously. A modified determination replaces silica gel-TLC with disposable Florisil columns, and steps were simplified to allow more analyses per unit time. Data from the modified determination are quantitatively compatible with data from older and tedious procedures. This determination was used for blood from 36 diverse patients with allergies. The mean CoQ10 blood level of these patients is not different from the mean level of so-called normal individuals, but approximately 40% (14/36) of these allergic patients had levels up to 0.65 micrograms/ml, which is the level of dying class IV cardiac patients. The biosynthesis of CoQ10 in human tissues is a complex process that requires several vitamins and micronutrients, so that countless vitamin-unsupplemented Americans may be deficient in CoQ10. The relationship of allergies to autoimmune mechanisms and immunity, and the established relationship of CoQ10 to immune states, may be a rationale for therapeutic trials of administering CoQ10 to patients with allergies who have low CoQ10 blood levels and are very likely deficient.


Biochemical deficiencies of coenzyme Q10 in HIV- infection and exploratory treatment.

Biochem Biophys Res Commun (UNITED STATES) Jun 16 1988, 153 (2) p888-96

AIDS patients (2 groups) had a blood deficiency (p less than 0.001) of coenzyme Q10 vs. 2 control groups. AIDS patients had a greater deficiency (p less than 0.01) than ARC patients. ARC patients had a deficiency (p less than 0.05) vs. control. HIV-infected patients had a deficiency (p less than 0.05) vs. control. The deficiency of CoQ10 increased with the increased severity of the disease, i.e., from HIV positive (no symptoms) to ARC (constitutional symptoms, no opportunistic infection or tumor) to AIDS (HIV infection, opportunistic infection and/or tumor). This deficiency, a decade of data on CoQ10 on the immune system, on IgG levels, on hematological activity constituted the rationale for treatment with CoQ10 of 7 patients with AIDS or ARC. One was lost to follow-up; one expired after stopping CoQ10; 5 survived, were symptomatically improved with no opportunistic infection after 4-7 months. In spite of poor compliance of 5/7 patients, the treatment was very encouraging and at times even striking.


Immunological senescence in mice and its reversal by coenzyme Q10.

Mech Ageing Dev (SWITZERLAND) Mar 1978, 7 (3) p189-97

A pronounced suppression of the humoral, hemolytic, primary immune response in old (22 months) mice was demonstrated as compared with this response in young (10 weeks) mice. The suppression is associated with a lower thymus weight: body weight ratio. In contrast, the ratio spleen weight: body weight and liver weight: body weight in 10 weeks and 22 months old mice remain almost constant. A single administration of coenzyme Q10--a non-toxic, non- specific stimulant of the host defense system--partly compensates the age-determined suppression of the humoral, immune response. This suppression probably results from an age-dependent imbalance of T cells: B cells ratio and a decline of their immunological responsiveness which is compensated by the administration of coenzyme Q10.


Treatment of essential hypertension with coenzyme Q10

Mol Aspects Med (ENGLAND) 1994, 15 Suppl pS265-72

A total of 109 patients with symptomatic essential hypertension presenting to a private cardiology practice were observed after the addition of CoQ10 (average dose, 225 mg/day by mouth) to their existing antihypertensive drug regimen. In 80 per cent of patients, the diagnosis of essential hypertension was established for a year or more prior to starting CoQ10 (average 9.2 years). Only one patient was dropped from analysis due to noncompliance. The dosage of CoQ10 was not fixed and was adjusted according to clinical response and blood CoQ10 levels. Our aim was to attain blood levels greater than 2.0 micrograms/ml (average 3.02 micrograms/ml on CoQ10). Patients were followed closely with frequent clinic visits to record blood pressure and clinical status and make necessary adjustments in drug therapy. Echocardiograms were obtained at baseline in 88% of patients and both at baseline and during treatment in 39% of patients. A definite and gradual improvement in functional status was observed with the concomitant need to gradually decrease antihypertensive drug therapy within the first one to six months. Thereafter, clinical status and cardiovascular drug requirements stabilized with a significantly improved systolic and diastolic blood pressure. Overall New York Heart Association (NYHA) functional class improved from a mean of 2.40 to 1.36 (P < 0.001) and 51% of patients came completely off of between one and three antihypertensive drugs at an average of 4.4 months after starting CoQ10. Only 3% of patients required the addition of one antihypertensive drug. In the 9.4% of patients with echocardiograms both before and during treatment, we observed a highly significant improvement in left ventricular wall thickness and diastolic function. (ABSTRACT TRUNCATED AT 250 WORDS)


Coenzyme Q10 in essential hypertension

Mol Aspects Med (ENGLAND) 1994, 15 Suppl ps257-63

This study was undertaken to clarify the mechanism of the antihypertensive effect of coenzyme Q10 (CoQ10). Twenty- six patients with essential arterial hypertension were treated with oral CoQ10, 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and high-density lipoprotein (HDL) cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period. At the end of the treatment, systolic blood pressure (SBP) decreased from 164.5 +/- 3.1 to 146.7 +/- 4.1 mmHg and diastolic blood pressure (DBP) decreased from 98.1 +/- 1.7 to 86.1 +/- 1.3 mmHg (P < 0.001). Plasma CoQ10 values increased from 0.64 +/- 0.1 microgram/ml to 1.61 +/- 0.3 micrograms/ml (P < 0.02). Serum total cholesterol decreased from 222.9 +/- 13 mg/dl to 213.3 +/- 12 mg/dl (P < 0.005) and serum HDL cholesterol increased from 41.1 +/- 1.5 mg/dl to 43.1 +/- 1.5 mg/dl (P < 0.01). In a first group of 10 patients serum sodium and potassium, plasma clinostatic and orthostatic renin activity, urinary aldosterone, 24-hour sodium and potassium were determined before and at the end of the 10-week period. In five of these patients peripheral resistances were evaluated with radionuclide angiocardiography. Total peripheral resistances were 2,283 +/- 88 dyne.s.cm-5 before treatment and 1,627 +/- 158 dyn.s.cm-5 after treatment (P < 0.02). Plasma renin activity, serum and urinary sodium and potassium, and urinary aldosterone did not change. In a second group of 11 patients, plasma endothelin, electrocardiogram, two-dimensional echocardiogram and 24- hour automatic blood pressure monitoring were determined. (ABSTRACT TRUNCATED AT 250 WORDS)


Usefulness of coenzyme Q10 in clinical cardiology: a long-term study

Mol Aspects Med (ENGLAND) 1994, 15 Suppl ps165-75

Over an eight year period (1985-1993), we treated 424 patients with various forms of cardiovascular disease by adding coenzyme Q10 (CoQ10) to their medical regimens. Doses of CoQ10 ranged from 75 to 600 mg/day by mouth (average 242 mg). Treatment was primarily guided by the patient's clinical response. In many instances, CoQ10 levels were employed with the aim of producing a whole blood level greater than or equal to 2.10 micrograms/ml (average 2.92 micrograms/ml, n = 297). Patients were followed for an average of 17.8 months, with a total accumulation of 632 patient years. Eleven patients were omitted from this study: 10 due to non-compliance and one who experienced nausea. Eighteen deaths occurred during the study period with 10 attributable to cardiac causes. Patients were divided into six diagnostic categories: ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), primary diastolic dysfunction (PDD), hypertension (HTN), mitral valve prolapse (MVP) and valvular heart disease (VHD). For the entire group and for each diagnostic category, we evaluated clinical response according to the New York Heart Association (NYHA) functional scale, and found significant improvement. Of 424 patients, 58 per cent improved by one NYHA class, 28% by two classes and 1.2% by three classes. A statistically significant improvement in myocardial function was documented using the following echocardiographic parameters: left ventricular wall thickness, mitral valve inflow slope and fractional shortening. Before treatment with CoQ10, most patients were taking from one to five cardiac medications. During this study, overallmedication requirements dropped considerably: 43% stopped between one and three drugs. Only 6% of the patients required the addition of one drug. No apparent side effects from CoQ10 treatment were noted other than a single case of transient nausea. In conclusion, CoQ10 is a safe and effective adjunctive treatment for a broad range of cardiovascular diseases, producing gratifying clinical responses while easing the medical and financial burden of multidrug therapy.


Influence of coenzyme Q-10 on the hypotensive effects of enalapril and nitrendipine in spontaneously hypertensive rats.

Pol J Pharmacol (POLAND) Sep-Oct 1994, 46 (5) p457-61

Administration of coenzyme Q-10 (10 mg/kg) once day for 4 weeks decreased the arterial blood pressure in SHR's. Enalapril and nitrendipine administered in a single dose caused significant decrease of blood pressure. Application of enalapril and nitrendipine to rats chronically pretreated with coenzyme Q-10 revealed, that the maximal hypotensive effect was not greater, but it lasted much (ca. 2-times) longer. Independently of mechanism of this interaction it may be suggested that the chronic administration of coenzyme Q-10 would create the possibility of significant decrease of the frequency of some antihypertensive drug administration.


Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment.

Clin Investig (GERMANY) 1993, 71 (8 Suppl) pS140-4

Symptoms of fatigue and activity impairment, atypical precordial pain, and cardiac arrhythmia frequently precede by years the development of congestive heart failure. Of 115 patients with these symptoms, 60 were diagnosed as having hypertensive cardiovascular disease, 27 mitral valve prolapse syndrome, and 28 chronic fatigue syndrome. These symptoms are common with diastolic dysfunction, and diastolic function is energy dependent. All patients had blood pressure, clinical status, coenzyme Q10 (CoQ10) blood levels and echocardiographic measurement of diastolic function, systolic function, and myocardial thickness recorded before and after CoQ10 replacement. At control, 63 patients were functional class III and 54 class II; all showed diastolic dysfunction; the mean CoQ10 blood level was 0.855 micrograms/ml; 65%, 15%, and 7% showed significant myocardial hypertrophy, and 87%, 30%, and 11% had elevated blood pressure readings in hypertensive disease, mitral valve prolapse and chronic fatigue syndrome respectively. Except for higher blood pressure levels and more myocardial thickening in the hypertensive patients, there was little difference between the three groups. CoQ10 administration resulted in improvement in all; reduction in high blood pressure in 80%, and improvement in diastolic function in all patients with follow-up echocardiograms to date; a reduction in myocardial thickness in 53% of hypertensives and 36% of the combined prolapse and fatigue syndrome groups; and a reduced fractional shortening in those high at control and an increase in those initially low. (ABSTRACT TRUNCATED AT 250 WORDS)


Muscle fibre types, ubiquinone content and exercise capacity in hypertension and effort angina.

Ann Med (FINLAND) Aug 1991, 23 (3) p339-44

The composition of skeletal muscle fibre expressed as a percentage of slow twitch (ST), type I or red and fast twitch (FT), type II or white were determined in patients with hypertension (HT) or with severe ischaemic heart disease (IHD) and compared to age matched controls. Similarly, exercise capacity expressed as the cycle intensity eliciting A blood lactate concentration corresponding to 2.0 mmol x 1-1 were compared with healthy controls. Both patient groups had a higher percentage of FT fibres with relatively lower exercise capacities than their controls. The exercise capacities were reduced even when the relationship of decreased capacity with the percentage of increased FT was considered. There was an increase IHD but not in HT in patients with fibre subgroup FTc, which most probably reflected fibre trauma. Both patient groups were low in the skeletal muscle mitochondrial electron carrier and unspecific antioxidant ubiquinone, coenzyme Q10 or CoQ10. Patients with IHD but not HT showed, however, a faster fall in the ratio CoQ10 over ST% the higher the percentage value of ST. The ratio reflects the antioxidant activity related to CoQ10 in the fibre hosting most of the oxidative metabolism. A low ratio indicates a risk of metabolic lesion and cell trauma. This could explain fibre plasticity and offer an alternative cause to heredity in elucidating in deviating muscle fibre composition in patients with HT and IHD.


Effect of coenzyme Q10 on structural alterations in the renal membrane of stroke-prone spontaneously hypertensive rats

Biochem Med Metab Biol (UNITED STATES) Apr 1991, 45 (2) p216-26

To test the hypothesis that structural abnormalities exist in the kidney membrane of spontaneously hypertensive rats, we examined the effect of long-term administration of coenzyme Q10 on membrane lipid alterations in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP). As compared with normotensive Wistar-Kyoto rats, renal membrane phospholipids, especially phosphatidylcholine and phosphatidylethanolamine, decreased and renal phospholipase A2 activity was enhanced with age in untreated SHRSP. Treatment with coenzyme Q10 attenuated the elevation of blood pressure, the membranous phospholipid degradation, and the enhanced phospholipase A2 activity. These results suggest that one factor contributing to the progress of hypertension is a structural membrane abnormality that alters the physical and functional properties of the cell membrane, and coenzyme Q10 might protect the renal membrane from damage due to hypertension in SHRSP.


Co-enzyme Q10: a new drug for cardiovascular disease

J Clin Pharmacol (UNITED STATES) Jul 1990, 30 (7) p596-608

Co-enzyme Q10 (ubiquinone) is a naturally occurring substance which has properties potentially beneficial for preventing cellular damage during myocardialischemia and reperfusion. It plays a role in oxidative phosphorylation and has membrane stabilizing activity. The substance has been used in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure. Its clinical importance is now being established in clinical trails worldwide. (133 Refs.)


Coenzyme Q10: a new drug for myocardial ischemia?

Med Clin North Am (UNITED STATES) Jan 1988, 72 (1) p243-58

A biochemical rationale for using CoQ in treating certain cardiovascular diseases has been established. CoQ subserves an endogenous function as an essential cofactor in several metabolic pathways, particularly oxidative respiration. As an exogenous source in supraphysiologic doses, CoQ may have pharmacologic effects that are beneficial to tissues rendered ischemic and then reperfused. Its mechanism of action appears to be that of a free radical scavenger and/or direct membrane stabilizer. Initial clinical studies performed abroad and in the United States indicate that CoQ may be effective in treating certain patients with ischemic heart disease, congestive heart failure, toxin-induced cardiotoxicity, and possibly hypertension. The most intriguing property of CoQ is its potential to protect and preserve ischemic myocardium during surgery. Currently, CoQ is still considered an experimental agent and only further studies will determine whether it will be useful therapy for human cardiovascular disease states. (105 Refs.)


Clinical study of cardiac arrhythmias using a 24-hour continuous electrocardiographic recorder (5th report)-- antiarrhythmic action of coenzyme Q10 in diabetics.

Tohoku J Exp Med (JAPAN) Dec 1983, 141 Suppl p453-63

An investigation was undertaken to evaluate the antiarrhythmic effect of CoQ10 on VPBs using the Holter ECG, in 27 patients with no clinical findings of organic cardiopathies. As a result, the effect of CoQ10 on VPBs was considered beneficial in 6 (22%) of 27 cases, consisting of 1 patient with hypertension and 5 patients with DM. Even in the remaining 2 patients with DM, the frequency of VPBs was reduced by 50% or more during treatment with CoQ10. The mean reduction of VPBs frequency in the 5 responders plus these 2 patients with DM was 85.7%. These findings suggest that CoQ10 exhibits an effective antiarrhythmic action not merely on organic heart disease but also on VPBs supervening on DM.


Bioenergetics in clinical medicine. XVI. Reduction of hypertension in patients by therapy with coenzyme Q10.

Res Commun Chem Pathol Pharmacol (UNITED STATES) Jan 1981, 31 (1) p129-40

Six untreated hypertensive patients and ten on therapy, but having elevated blood pressures, were treated with coenzyme Q10 (CoQ10); 14/16 patients showed reductions (p less than 0.05-less than 0.001) in systolic pressures; 11/16 showed reductions (p less than 0.05-less than 0.001) in diastolic pressure; 9/10 showed reductions of elevated pressures to a normal range. By impedance cardiography and electrocardiography, there were no changes in cardiac outputs, stroke volumes and Heather Indices except for a few patients with changes of doubtful biological significance. 3/16 patients had exceptionally low basal specific activities of the succinate dehydrogenase- coenzyme Q10 reductase in blood which increased to a normal range on treatment. A greater deficiency of CoQ10 in the vascular system than inblood is likely. We consider that (1) the mechanism of reduction of elevated blood pressures by CoQ10 is based upon normalization or autoregulation of peripheral resistance rather than cardiac regulation, and (2) that the therapeutic activity of CoQ10 is not pharmacodynamic, but results from a translational increase in levels of CoQ10-enzymes in vascular tissue during ca. 4-12 weeks.


Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors.

Res Commun Chem Pathol Pharmacol (UNITED STATES) May 1977, 17 (1) p157-64

Adrenergic blockers for beta-receptors were studied for inhibition of mitochrondrial CoQ10-enzymes. These enzymes are indispensable for the bioenegetics of the myocardium. Propranolol is frequently used to treat hypertension; in some patients, it depresses myocardial function as an adverse reaction. This side effect may be related to the inhibition by propranolol of CoQ10-enzymes of the myocardium. Timolol showed negligible inhibition of the CoQ10-enzyme, NADH-oxidase. Metoprolol was less inhibitory than propranolol. Five alprenolols showed inhibition which approached that of propranolol. The 1-isomer of alprenolol showed weak inhibition of another CoQ10-enzyme, succinoxidase, but the other beta-blockers were essentially non-inhibitory to this enzyme. The drug of choice is timolol, based on negligible inhibition of these bioenergetic enzymes of the heart, which correlates with its pharmacologically low cardiac depressant effects.


Bioenergetics in clinical medicine. VIII. Adminstration of coenzyme Q10 to patients with essential hypertension.

Res Commun Chem Pathol Pharmacol (UNITED STATES) Aug 1976, 14 (4) p721-7

Coenzyme Q10 has been administered to five patients having essential hypertension and deficiencies of activity of succinate dehydrogenase-co-enzyme Q10 reductase in leucocyte preparations ranging from 20-40%. For a 74-year old male, the systolic pressure was reduced (p less than 0.001), the diastolic pressure was reduced (p less than 0.05), the specific activity of the coenzyme Q10-enzyme was increased (p less than 0.001), and the deficiency of coenzyme Q10 activity was negated (p less than 0.01). Four patients receiving CoQ10 for 3-5 months showed reductions (p less than 0.05 to p less than 0.001) of diastolic pressure, and 3 of these 4 showed reductions (p less than 0.05 to p less than 0.01) of diastolic pressure. Initial deficiencies of enzyme activity were reduced (p less than 0.01 to 0.05) in two patients. Three other patients did not show the high level of deficiency on treatment as initially observed. These effects of CoQ10 on the reduction of systolic and diastolic blood pressures, increase in CoQ10-enzyme activity, and reduction of CoQ10- deficiency are presumably due to improved bioenergetics through correction of a deficiency of coenzyme Q10.


Bioenergetics in clinical medicine. III. Inhibition of coenzyme Q10-enzymes by clinically used anti-hypertensive drugs

Res Commun Chem Pathol Pharmacol (UNITED STATES) Nov 1975, 12 (3) p533-40

Background data revealed that some American and Japanese patients with essential hypertension, including many who were not being treated with any anti-hypertensive drug, had a deficiency of coenzyme Q10. Eight clinically used anti-hypertensive drugs have now been tested for inhibition of two mitochondrial coenzyme Q10-enzymes of heart tissue, succinoxidase and NADH-oxidase. Diazoxide and propranolol significantly inhibited the CoQ10- succinoxidase and CoQ10-NADH-oxidase, respectively. Metoprolol did not inhibit succinoxidase, and was one- fourth as active as propranolol for inhibition of NADH- oxidase. Hydrochlorothiazide, hydralazine, ans clonidine also inhibited CoQ10-NADH-oxidase. Reserpine did not inhibit either CoQ10-enzyme, and methyldopa was a very eak inhibitor of succinoxidase. The internationally recognized clinical side-effects of propranolol may be due, in part, to inhibition of CoQ10-enzymes which are indispensable in the bioenergetics of cardiac function. A pre-existing deficiency of coenzyme Q10 in the myocardium of hypertensive patients could be augmented by subsequent treatment with propranolol, possibly to the life- threatening state described by others.


Bioenergetics in clinical medicine. Studies on coenzyme Q10 and essential hypertension.

Res Commun Chem Pathol Pharmacol (UNITED STATES) Jun 1975, 11 (2) p273-88

The specific activities (S.A.) of the succinate dehydrogenase-coenzyme Q10 (CoQ10) reductase of a control group of 65 Japanese adults and 59 patients having essential hypertension were determined. The mean S.A. of the hypertensive group was significantly lower (p less than 0.001) and the mean % deficiency of enzyme activity was significantly higher (p less than 0.001) than the values for the control group. These data on Japanese in Osaka agree with data on Americans in Dallas. Some patients showed no CoQ10-deficiency, and others showed definite deficiencies. Emphasizing the CoQ10-enzyme for patient selection, CoQ10 was administered to hypertensive patients. Four individuals showed significant but partial reductions of blood pressure. Monitoring the CoQ10-enzyme before, during, and after administration of CoQ10 indicated responses. The maintenance of high blood pressure could be primarily due to contraction of the arterial wall. Contraction or relaxation of an arterial wall is dependent upon bioenergetics, which also provide the energy for biosynthesis of angiotensin II, renin, aldosterone, and the energy for sodium and potassium transport. A clinical benefit from administration of CoQ10 to patients with essential hypertension could be based upon correcting a deficiency in bioenergetics, and point to possible combination treatments with a form of CoQ and anti-hypertensive drugs.


Plasma ubiquinol-10 is decreased in patients with hyperlipidaemia

Atherosclerosis (Ireland), 1997, 129/1 (119-126)

Ubiquinol-10, the reduced form of ubiquinone-10 (coenzyme Q10), is a potent lipophilic antioxidant present in nearly all human tissues. The exceptional oxidative lability of ubiquinol-10 implies that it may represent a sensitive index of oxidative stress. The present study was undertaken to assess the hypothesis that the level of ubiquinol-10 in human plasma can discriminate between healthy subjects and patients who are expected to be subjected to an increased oxidative stress in vivo. Using a newly developed method, we measured plasma ubiquinol-10 in 38 hyperlipidaemic patients with and without further complications, such as coronary heart disease, hypertension, or liver disease, and in 30 healthy subjects. The oxidizability of plasma samples obtained from hyperlipidaemic patients was found to be increased in comparison with control subjects, suggesting that the patients were subjected to a higher oxidative stress in vivo than the controls. Plasma ubiquinol-10, expressed as a percentage of total ubiquinol-10 + ubiquinone-10 or normalized to plasma lipids, was lower in the patients than in controls (P = 0.001 and 0.008, respectively). The proportion of ubiquinol-10 decreased in the order young controls aged controls hyperlipidaemic patients without complications hyperlipidaemic patients with complications (P = 0.003). A negative correlation was found between the proportion of ubiquinol-10 and plasma triglycerides. The hyperlipidaemic patients with hypertension had a lower proportion of ubiquinol-10 than subjects without. When the study population was divided into smokers and non-smokers, plasma ubiquinol-10 was found to be reduced amongst smokers, independently of whether it was expressed as a percentage of total ubiquinol-10 + ubiquinone-10 (P = 0.006) or normalized to plasma lipids (P = 0.009). These data suggest that the level of ubiquinol-10 in human plasma may represent a sensitive index of oxidative stress in vivo especially indicative of early oxidative damage. Measuring plasma ubiquinol-10 can be proposed as a practical approach to assess oxidative stress in humans.


Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex

BIOCHEM. BIOPHYS. RES. COMMUN. (USA), 1991, 176/2 (786-791)

Coenzyme Q10 (CoQ10) is indispensable to biochemical mechanisms of bioenergetics, and it has a non-specific role as an antioxidant. CoQ10 has shown a hematological activity for the human and has shown an influence on the host defense system. The T4/T8 ratios of lymphocytes are known to be low in patients with AIDS, ARC and malignancies. Our two patients with ARC have survived four- five years without any symptoms of adenopathy or infection on continuous treatment with CoQ10. We have newly found that 14 ordinary subjects responded to CoQ10 by increases in the T4/T8 ratios and an increase in blood levels of CoQ10; both by p < 0.001. This knowledge and survival of two ARC patients for four-five years on CoQ10 without symptoms, and new data on increasing ratios of T4/T8 lymphocytes in the human by treatment with CoQ10 constitute a rationale for new double blind clinical trials on treating patients with AIDS, ARC and diverse malignancies with CoQ10.


The clinical and hemodynamic effects of Coenzyme Q10 in congestive cardiomyopathy

American Journal of Therapeutics (USA), 1997, 4/2-3 (66-72)

Despite major advances in treatment congestive heart failure (CHF) is still one of the major causes of morbidity and mortality. Coenzyme Q10 is a naturally occurring substance that has antioxidant and membrane stabilizing properties. Administration of coenzyme Q10 in conjunction with standard medical therapy has been reported to augment myocardial kinetics, increase cardiac output, elevate the ischemic threshold, and enhance functional capacity in patients with congestive heart failure. The aim of this study was to investigate some of these claims. Seventeen patients (mean New York Heart Association functional class 3.0 plus or minus 0.4) were enrolled in an open-label study. After 4 months of coenzyme Q10 therapy, functional class improved 20% (3.0 plus or minus 0.4 to 2.4 plus or minus 0.6, p < 0.001) and there was a 27% improvement in mean CHF score (2.8 plus or minus 0.4 to 2.2 plus or minus 0.4, p < 0.001). Percent change in the resting variables included the following: left ventricular ejection fraction (LVEF), +34.8%; cardiac output, +15.7%; stroke volume index, +18.9%; end- diastolic volume area, -8.4%; systolic blood pressure (SBP), -4.4%; and E (max), (SBP + end-systolic volume index (ESVI)) +11.7%. MV (O2) decreased by 5.3% (31.9 plus or minus 2.6 to 30.2 plus or minus 2.4, p = NS). Therapy with coenzyme Q10 was associated with a mean 25.4% increase in exercise duration and a 14.3% increase in workload. Percent changes after therapy include the following: exercise LVEF, +24.6%; cardiac output, +19.1%; stroke volume index, +13.2%; heart rate, +6.5%; SBP, - 4.3%; SBP + ESVI, +18.6%; end-diastolic volume (EDV) area, -6.0%; MV (O2), -7.0%; and ventricular compliance (% Delta SV + EDV) improved 100%. In


Summary

, coenzyme Q10 therapy is associated with significant functional, clinical, and hemodynamic improvements within the context of an extremely favorable benefit-to-risk ratio. Coenzyme Q10 enhances cardiac output by exerting a positive inotropic effect upon the myocardium as well as mild vasodilatation.


NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings.

J Inherit Metab Dis (NETHERLANDS) 1996, 19 (5) p675-86

Twelve patient cell lines with biochemically proven complex I deficiency were compared for clinical presentation and outcome, together with their sensitivity to galactose and menadione toxicity. Each patient had elevated lactate to pyruvate ratios demonstrable in fibroblast cultures. Each patient also had decreased rotenone-sensitive NADH-cytochrome c reductase (complexes I and III) with normal succinate cytochrome c reductase (complexes II and III) and cytochrome oxidase (complex IV) activity in cultured skin fibroblasts, indicating a deficient NADH-coenzyme Q reductase (complex I) activity. The patients fell into five categories: severe neonatal lactic acidosis; Leigh disease; cardiomyopathy and cataracts; hepatopathy and tubulopathy; and mild symptoms with lactic acidaemia. Cell lines from 4 out of the 12 patients were susceptible to both galactose and menadione toxicity and 3 of these also displayed low levels of ATP synthesis in digitonin-permeabilized skin fibroblasts from a number of substrates. This study highlights the heterogeneity of complex I deficiency at the clinical and biochemical level.


Effect of protection and repair of injury of mitochondrial membrane-phospholipid on prognosis in patients with dilated cardiomyopathy.

Blood Press Suppl (NORWAY) 1996, 3 p53-5

We have already proved that the mitochondrial membrane- phospholipid (MMP) injury changes of peripheral lymphocytes in patients with heart failure can be used as an injury indicator of myocardia, and are related to the long-term prognosis. In the present study, MMP localization of the peripheral lymphocytes was performed by modified Demer's tricomplex flocculation method, and we compared the changes, after classification, between the pre-treatment and the 12-week post-treatment, of coenzyme Q10 (Co.Q10) and captopril in 61 hospitalized patients with dilated cardiomyopathy (DCM). They were followed up for 16.1 +/- 7.8 months (mean). The results showed that compared with the placebo, Co.Q10 and captopril could significantly protect against and repair MMP injury and improve the heart function of patients with DCM after 12 weeks, and the 2-year survival rate rose significantly by 72.7% for Co.Q10, and 64.0% for captopril, vs 24.7% for placebo. As for Longrank test, X2 equals 4.660 and 6.318, respectively, with both p < 0.05. The aforementioned results indicate that MMP injury of peripheral lymphocytes can predict the prognosis of the patients with DCM, thus the protection and repairment of MMP injury can improve the life-quality and prolong the life-span of thepatients.


[Therapeutic effects of coenzyme Q10 on dilated cardiomyopathy: assessment by 123I-BMIPP myocardial single photon emission computed tomography (SPECT): a multicenter trial in Osaka University Medical School Group]

Kaku Igaku (JAPAN) Jan 1996, 33 (1) p27-32

To evaluate therapeutic effects of Cenzyme Q10 (CoQ10), 15 patients with dilated cardiomyopathy were investigated by 123I-BMIPP myocardial single photon emission computed tomography (SPECT). The BMIPP defect score was determined semiquantitatively by using representative short and long axial SPECT images. Mean BMIPP defect score with CoQ10 treatment was significantly low, 7.7 +/- 6.1 compared to 12.7 +/- 7.4 without CoQ10 treatment. On the other hand, in 8 patients of dilated cardiomyopathy, % fractional shortening using echocardiography was not different before and after CoQ10 treatment. In conclusion, 123I-BMIPP myocardial SPECT was proved to be sensitive to evaluate the therapeutic effects of CoQ10, which improve myocardial mitochondrial function, in the cases of dilated cardiomyopathy.


Italian multicenter study on the safety and efficacy of COENZYME Q10 as adjunctive therapy in heart failure.

Mol Aspects Med (ENGLAND) 1994, 15 Suppl ps287-94

Digitalis, diuretics and vasodilators are considered the standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of COENZYME Q10 (CoQ10) adjunctive treatment in congestive heart failure that had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2664 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing study in 173 Italian centers. The daily dosage of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two-to seven-point scales. The results show a low incidence of side effects: 38 adverse effects were reported in 36 patients (1.5%) of which 22 events were considered as correlated to the test treatment. After three months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 78.1%, oedema 78.6%, pulmonary rales77.8%, enlargement of liver area 49.3%, jugular reflux 71.81%, dyspnoea 52.7%, palpitations 75.4%, sweating 79.8%, subjective arrhytmia 63.4%, insomnia 662.8%, vertigo 73.1% and nocturia 53.6%. Moreover we observed a contemporary improvement of at least three symptoms in 54% of patients; this could be interpreted as an index of improved quality of life.

Coenzyme Q10 (also known as ubiquinone, ubidecarenone, or CoQ10) is a benzoquinone, where the "Q" and the "10" in the name refer to the quinone chemical group and the 10 isoprenyl chemical subunits, respectively.

This vitamin-like substance is, by nature, present in all human cells and responsible for the production of the body's own energy. In each human cell food energy is converted into energy for our body in the mitochondria with the aid of CoQ10. 95% of all our body's energy requirements (ATP) is converted with the aid of CoQ10[1][2]. Therefore those organs with the highest energy requirements - such as the heart, the lungs and the liver - have been shown to have the highest CoQ10 concentrations[3][4][5].

CoQ is found in the membranes of endoplasmic reticulum, peroxisomes, lysosomes, vesicles and notably the inner membrane of the mitochondrion where it is an important part of the electron transport chain; there it passes reducing equivalents to acceptors such as Coenzyme Q : cytochrome c - oxidoreductase:

CoQH2+ 2 FeIII-cytochrome c → CoQ + 2 FeII-cytochrome c
CoQ is also essential in the formation of the apoptosome along with other adapter proteins. The loss of trophic factors activates pro-apoptotic enzymes, causing the breakdown of mitochondria.

Antioxidant role of CoQ10 in the body

Apart from being a cofactor in the mitochondrial electron transport chain, CoQ10 in its reduced form (ubiquinol or CoQ10 H2) serves as an important antioxidant in both mitochondria and lipid membranes, where it protects our cells in their battle against the destructive effects of free radicals. In human LDL it affords protection against the oxidative modifications of LDL themselves, thus lowering their atherogenic potency [9]. CoQ10 is essential in vitamin E regeneration. Ubiquinol, inhibits protein and lipid oxidation in cell membranes, and helps to minimize oxidative injury to DNA[10]. CoQ10 is an integral part of the respiratory chain and thereby located exactly where the free radicals are generated, in the mitochondria. These endogeneously produced free radicals are considered as an import factor of the aging process [11].

Supplementation

Supplementation of Coenzyme Q10 is a treatment for some of the very rare and serious mitochondrial disorders and other metabolic disorders, where patients are not capable to produce enough coenzyme Q10 because of their disorder. Coenzyme Q10 is then prescribed by a medical doctor. [12]

Because of its ability to transfer electrons and therefore act as an antioxidant, Coenzyme Q is also used as a dietary supplement. Young people are able to make Q10 from the lower numbered ubiquinones such as Q6 or Q8.[citation needed] The sick and elderly may not be able to make enough, thus Q10 becomes a vitamin later in life and in illness.[citation needed]

Supplementation of Coenzyme Q10 has been found to have a beneficial effect on the condition of some sufferers of migraine headaches. So far three studies have been done, of which two were small, did not have a placebo group, were not randomized and were open label (migraine patients knew they were taking coenzyme Q10), and one was a double-blind, randomized, placebo-controlled trial in a very small group of 42 patients. [13].

It is also being investigated as a treatment for cancer, and as relief from cancer treatment side effects.[14]

Recent studies have shown that the antioxidant properties of Coenzyme Q10 benefit the body and the brain in animal models.[15] Some of these studies indicate that Coenzyme Q10 protects the brain from neurodegenerative disease such as Parkinsons[16], although it does not relieve the symptoms[17]. Another recent study shows a survival benefit after cardiac arrest if coenzyme Q10 is administered in addition to commencing active cooling (to 32-34 degrees Celsius).[18]

There are several reports concerning the effect of CoQ10 on blood pressure in human studies (for review: [19]). In a recent meta-analysis of the clinical trials of CoQ10 for hypertension a research group led by Professor FL Rosenfeldt (from the Cardiac Surgical Research Unit, Alfred Hospital, Melbourne, Australia) reviewed all published trials of Coenzyme Q10 for hypertension, assessed overall efficacy and consistency of therapeutic action and side effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study and eight open label studies. The research group concluded that coenzyme Q10 has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side effects. [20]

Biosynthesis

The benzoquinone portion of Coenzyme Q10 is synthesized from tyrosine, while the isoprene sidechain is synthesized from acetyl-CoA through the mevalonate pathway. The mevalonate pathway is used for the first steps of cholesterol biosynthesis.

Inhibition by statins and beta blockers
Coenzyme Q10 shares a common biosynthetic pathway with cholesterol. The synthesis of an intermediary precursor of Coenzyme Q10, mevalonate, is inhibited by some beta blockers, blood pressure lowering medication,[21] and statins, a class of cholesterol lowering drugs.[22] Statins can reduce serum levels of coenzyme Q10 by up to 40%.[23] Some research suggests the logical option of supplementation with coenzyme Q10 as a routine adjunct to any treatment which may reduce endogenous production of coenzyme Q10, based on a balance of likely benefit against very small risk.[24][25]

References
^ Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271: 195-204, 1995
^ Dutton PL, Ohnishi T, Darrouzet E, Leonard, MA, Sharp RE, Cibney BR, Daldal F and Moser CC. 4 Coenzyme Q oxidation reduction reactions in mitochondrial electron transport (pp 65-82) in Coenzyme Q: Molecular mechanisms in health and disease edited by Kagan VE and Quinn PJ, CRC Press (2000), Boca Raton
^ Okamoto, T.et al (1989) Interna.J.Vit.Nutr.Res.,59,288-292
^ Aberg,F.et al (1992)Archives of Biochemistry and Biophysics, 295, 230-234
^ Shindo, Y., Witt, E., Han, D., Epstein, W., and Packer, L., Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin, Invest. Dermatol., 102 (1994) 122-124.
^ Crane F, Hatefi Y, Lester R, Widmer C (1957). "Isolation of a quinone from beef heart mitochondria". Biochim Biophys Acta 25 (1): 220-1. PMID 13445756. 
^ a b Peter H. Langsjoen, "Introduction to Coezyme Q10"
^ Wolf DE, Hoffman CH, Trenner NR, Arison BH, Shunk CH, Linn BD, McPherson JF, and Folkers K. Structure studies on the coenzyme Q group. J Am Chem Soc 1958: 80:4752.
^ Alleva R, Tomasetti M, Battino M, Curatola G, Littarru GP, Folkers K: The roles of coenzyme Q10 and vitamin E on peroxidation of human low density subfractions. Proc Nat Acad Sci. USA, 92: 9388-9391, 1995
^ Tomasetti M., Littarru G.P., Stocker R., Alleva R.: Coenzyme Q10 enrichment decreases oxidative DNA damage in human lymphocytes. Free Radic Biol Med. 27: 1027-1032, 1999
^ Lenaz G, Bovina C, D'Aurelio M, Fato R, Formiggini G, Genova ML, Giuliano G, Pich MM, Paolucci U, Castelli GP, Ventura B: Role of mitochondria in oxidative stress and aging. Ann N Y Acad Sci 959:199-213, 2002
^ Berbel-Garcia, A.; et al. (July 2004). "Coenzyme Q 10 improves lactic acidosis, strokelike episodes, and epilepsy in a patient with MELAS". Clinical Neuropharmacology 27: 187-191. PMID 15319706. Retrieved on 2006-12-01. 
^ Rozen T, Oshinsky M, Gebeline C, Bradley K, Young W, Shechter A, Silberstein S (2002). "Open label trial of coenzyme Q10 as a migraine preventive". Cephalalgia 22 (2): 137-41. PMID 11972582. 
^ Katsuhisa Sakano, Mami Takahashi, Mitsuaki Kitano, Takashi Sugimura, Keiji Wakabayashi: Suppression of Azoxymethane-induced Colonic Premalignant Lesion Formation by Coenzyme Q10 in Rats. Asian Pacific J Cancer Prev, 7, 599-603, 2006
^ Matthews, R. T.; et al. (July 1998). "Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects". PNAS 95: 8892-8897. Retrieved on 2006-12-01. 
^ Biol Signals Recept. 2001 May-Aug;10(3-4):224-53
^ Alexander Storch, MD; Wolfgang H. Jost, MD; Peter Vieregge, MD; Jörg Spiegel, MD; Wolfgang Greulich, MD; Joachim Durner, MD; Thomas Müller, MD; Andreas Kupsch, MD; Henning Henningsen, MD; Wolfgang H. Oertel, MD; Gerd Fuchs, MD; Wilfried Kuhn, MD; Petra Niklowitz, MD; Rainer Koch, PhD; Birgit Herting, MD; Heinz Reichmann, MD; for the German Coenzyme Q10 Study Group (May 14, 2007). Randomized, Double-blind, Placebo-Controlled Trial on Symptomatic Effects of Coenzyme Q10 in Parkinson Disease. Archives of Neurologu.
^ Damian, M. S.; et al. (July 2004). "Coenzyme Q10 Combined With Mild Hypothermia After Cardiac Arrest". Circulation, American Heart Foundation 110: 3011-3016. Retrieved on 2006-12-01. 
^ Cupp MJ and Tracy TS. Chapter 4: Coenzyme Q10 (Ubiquinone, Ubidecarenone), pp 53-85 in Dietary Supplements edited by Cupp MJ and Tracy TS Humana press, Totowa, New Jersey (2003)
^ Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong J-Y, Watts GF. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Human Hypertension 21: 297-306, 2007
^ Kishi T, Watanabe T, Folkers K (1977). "Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors". Res Commun Chem Pathol Pharmacol 17 (1): 157-64. PMID 17892. 
^ http://www.cholesterol-and-health.com/Synthesis-Of-Cholesterol.html
^ Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco A, Littarru G (1993). "Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study". J Clin Pharmacol 33 (3): 226-9. PMID 8463436. 
^ Sarter B (2002). "Coenzyme Q10 and cardiovascular disease: a review". J Cardiovasc Nurs 16 (4): 9-20. PMID 12597259. 
^ Thibault A, Samid D, Tompkins A, Figg W, Cooper M, Hohl R, Trepel J, Liang B, Patronas N, Venzon D, Reed E, Myers C (1996). "Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer". Clin Cancer Res 2 (3): 483-91. PMID 9816194

Myocardial preservation by therapy with coenzyme Q10 during heart surgery

USA CLIN. INVEST. SUPPL. (Germany), 1993, 71/8 (S 155-S 161)

Coenzyme Q10 (CoQ10) is a natural and essential cofactor in the heart. It is the primary redox coupler in the respiratory chain, a potent free radical scavenger, and a superoxide inhibitor. In this study the myocardial protective effects of CoQ10 were determined in high-risk (n = 10) patients during heart surgery compared to that found in placebo controls (n = 10). In both groups, there was a blood CoQ10 deficiency (<0.6 microg/ml), low cardiac index (CI < 2.4 l/m2 per minute), and low left ventricular ejection fraction (LVEF <35%) before treatment. CoQ10 (100 mg per day) was given orally for 14 days before and 30 days after surgery. Presurgical CoQ10 treatment significantly (P < 0.01) improved blood and myocardial CoQ10 and myocardial ATP compared to that found in the control group. Cardiac functions (CI and LVEF) were improved but not significantly. After cardiac cooling, rewarming, and reperfusion; blood and tissue CoQ10 and tissue ATP levels were maintained in the normal ranges in the CoQ10 patients. Cardiac pumping (CI) and LVEF were significantly (P < 0.01) improved. The recovery course was short (3-5 days) and uncomplicated. In the control group blood and tissue CoQ10, tissue ATP levels, and cardiac functions were depressed after surgery. The recovery course was long (15-30 days) and complicated. Positive relationships between blood and myocardial CoQ10, myocardial ATP, cardiac function, and the postoperative recovery time and course found in both study groups show the therapeutic benefits of CoQ10 in preserving the myocardium during heart surgery. CoQ10 treatment is especially indicated in high-risk cardiac surgery patients who have a natural or clinically induced CoQ10 deficiency.


Effect of CoQ10 on myocardial ischemia/reperfusion injury in the isolated rat heart

Journal of the Japanese Association for Thoracic Surgery (Japan), 1995, 43/4 (466-472)

It has been reported to CoQ10, ubiquinone may have a protective effect on the mitochrondrial injury induced by myocardial ischemia and reperfusion during open heart surgery. The purpose of this study was to investigate whether CoQ10 may enhance myocardial protection when given before ischemia, during ischemia or during reperfusion in the isolated working rat heart. Hearts (n = 6 - 9/group) from male Wistar rats were aerobically (37degreeC) perfused (20 min) with bicarbonate buffer. In the first series of studies, this was followed by a 3 min infusion of St. Thomas' Hospital cardioplegic solution containing various concentrations of CoQ10. Hearts were then subjected to 39 min of normothermic (37degreeC) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). The percent recovery of aortic flow (% AF) was 50.5 plus or minus 3.3% in the CoQ10, free controls versus 55.9 plus or minus 4.44, 62.1 plus or minus 5.4, 71.4 plus or minus 3.1% ((*) p < 0.05) in the 29, 44 and 58 micromol/L CoQ10 groups, respectively. Creatine kinase (CK) leakage during Langendorff reperfusion had a tendency to decrease in the 58 micromol/L group. In the second series of studies, 3 min of cardioplegia with 0 or 58 micromol/L of CoQ10 and 20 min working reperfusion. % AF was 53.2 plus or minus 2.7 and 39.2 plus or minus 7.1% in the 0 and 58 micromol/L CoQ10 groups, respectively. CK leakage had a tendency to increase in the 58 micromol/L group. In the third series of studies, 7.5 micromol of CoQ10 was administered over 10 min prior to a 3 min infusion of St. Thomas' Hospital cardioplegic solution. Hearts were then subjected to 36 min of normothermic (37degreeC) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). %AF was 43.8 plus or minus 1.8 and 47.5 plus or minus leakage between the two groups. Thus CoQ10 when given during ischemia, enhanced myocardial protection. This might indicate that CoQ10 could play an important role in the protective effect on mitochondrial dysfunction during myocardial ischemia.


Measurement of the ratio between the reduced and oxidized forms of coenzyme Q10 in human plasma as a possible marker of oxidative stress.

J Lipid Res (UNITED STATES) Jan 1996, 37 (1) p67-75

It has been postulated that lipid peroxidation plays a crucial role in the pathogenesis of atherosclerosis. As CoQ10H2 (reduced form of coenzyme Q10) is easily oxidized to CoQ10 (oxidized form of coenzyme Q10), it has been proposed that the CoQ10H2/CoQ10 ratio may be used as a possible marker of in vivo oxidative stress. However, sample preparation has an important effect on the redox status of coenzyme Q10 due to the extreme sensitivity of CoQ10H2 towards oxidation. We now report a rapid, simple isocratic HPLC procedure for the determination of CoQ10H2 and CoQ10 in plasma isopropanol extracts, and we used this method to investigate conditions by which the CoQ10H2/CoQ10 ratio can be reliably measured. Our results indicate that CoQ10H2 is unstable in whole blood, plasma, and isopropanol extracts; subsequently the CoQ10H2/CoQ10 ratio changes considerably soon after a blood sample has been obtained. The time period since blood sampling and HPLC analysis, as well as the sample pretreatment procedure, are two factors that have a profound effect on the pre-analytical variation in the determination of the CoQ10H2/CoQ10 ratio. If these two factors are properly controlled, the CoQ10H2/CoQ10 ratio may be a sensitive and practical way to measure in vivo oxidative stress. Furthermore, this indicator is independent from plasma total cholesterol concentrations, implying that groups who differ with respect to cholesterol levels may be compared directly.


The role of free radicals in disease

Australian and New Zealand Journal of Ophthalmology (Australia), 1995, 23/1

Evidence is accumulating that most of the degenerative diseases that afflict humanity have their origin in deleterious free radical reactions. These diseases include atherosclerosis, cancer, inflammatory joint disease, asthma, diabetes, senile dementia, and degenerative eye disease. The process of biological ageing might also have a free radical basis. Most free radical damage to cells involves oxygen free radicals or, more generally, activated oxygen species (AOS) which include non-radical species such as singlet oxygen and hydrogen peroxide as well as free radicals. The AOS can damage genetic material, cause lipid peroxidation in cell membranes, and inactivate membrane-bound enzymes. Humans are well endowed with antioxidant defences against AOS; these antioxidants, or free radical scavengers, include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), beta-carotene, coenzyme Q10, enzymes such as catalase and superoxide dismutase, and trace elements including selenium and zinc. The eye is an organ with intense AOS activity, and it requires high levels of antioxidants to protect its unsaturated fatty acids. The human species is not genetically adapted to survive past middle age, and it appears that antioxidant supplementation of our diet is needed to ensure a more healthy elderly population.


Coenzyme Q10 and coronary artery disease

CLIN. INVEST. SUPPL. (Germany), 1993, 71/8

It has been postulated that oxidatively modified low- density lipoprotein (LDL) contributes to the genesis of atherosclerosis. Ubiquinone has been suggested to be an important physiological lipid-soluble antioxidant and is found in LDL fractions in the blood. We measured plasma level of ubiquinone using high-performance liquid chromatography and plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in 245 normal subjects (186 males, 59 females) and in 104 patients (55 males, 49 females) who had coronary artery disease not receiving pravastatin and 29 patients (12 males, 17 females) receiving pravastatin. In the normal subjects, the plasma ubiquinone levels did not vary with age. In the patient groups, the plasma total cholesterol and LDL levels were higher and the plasma ubiquinone level lower than in the normal subject group. The LDL/ubiquinone ratio was higher in the patient groups. We found that ubiquinone level, either alone or when expressed in relation to LDL levels, was significantly lower in the patient groups compared with the normal subject group. The 3-hydroxy-3-methylglutaryl coenzyme A (HMC CoA) reductase inhibitor is thought to prevent atherosclerosis, however, it also inhibits ubiquinone production. The present study revealed that HMG CoA reductase inhibitor decreased plasma cholesterol level, and that it did not improve either the ubiquinone level or the LDL/ubiquinone ratio. From these results, the LDL/ubiquinone ratio is likely to be a risk factor for atherogenesis, and administration of ubiquinone to patients at risk might be needed.


Isoprenoids (coQ10) in aging and neurodegeneration.

Neurochem Int (ENGLAND) Jul 1994, 25 (1) p35-8

During aging the human brain shows a progressive increase in levels of dolichol, a reduction in levels of ubiquinone, but relatively unchanged concentrations of cholesterol and dolichyl phosphate. In a neurodegenerative disease, Alzheimer's disease, the situation is reversed with decreased levels of dolichol and increased levels of ubiquinone. The concentrations of dolichyl phosphate are also increased, while cholesterol remains unchanged. This study shows that the isoprenoid changes in Alzheimer's disease differ from those occurring during normal aging and that this disease cannot, therefore, be regarded as a result of premature aging. The increase in the sugar carrier dolichyl phosphate may reflect an increased rate of glycosylation in the diseased brain and the increase in the endogenous anti-oxidant ubiquinone an attempt to protect the brain from oxidative stress, for instance induced by lipid peroxidation.


Muscle biopsy in Alzheimer's disease: Morphological and biochemical findings

CLIN. NEUROPATHOL. (Germany), 1991, 10/4 (171-176)

Recent evidences of a predisposing genetic factor associated with Alzheimer's disease (DAT) suggests that important alterations may be expressed in tissues other than the brain. We present morphological and biochemical studies on muscle obtained from ten patients with Alzheimer's disease and coeval controls. Muscle biopsy examination showed an increased subsarcolemmal mitochondrial oxidative activity in three patients. The biochemical studies showed an increased oxidative enzyme activity only in the DAT group. The CoQ10 level, studied so far in three DAT patients, was greatly reduced (similar50%) compared with controls. Possible new peripheral markers in Alzheimer's disease will be discussed.


Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy

Biochemical and Biophysical Research Communications (USA), 1996, 224/2 (358-361)

In the human, coenzyme Q10 (vitamin Q10) is biosynthesized from tyrosine through a cascade of eight aromatic precursors. These precursors indispensably require eight vitamins, which are tetrahydrobiopterin, vitamins B6 C, B2, B12, folic acid, niacin, and pantothenic acid as their coenzymes. Three of these eight vitamins (the coenzyme B6 and the coenzymes niacin and folic acid) are indispensable in the biosynthesis of the four bases (thymidine, guanine, adenine, and cytosine) of DNA. One or more of the three vitamins required for DNA are known to cause abnormal pairing of the four bases, which can then result in mutations and the diversity of cancer. The coenzyme B6 required for the conversion of tyrosine to p- hydroxybenzoic acid, is the first coenzyme required in the cascade of precursors. A deficiency of the coenzyme B6 can cause dysfunctions, prior to the formation of vitamin Q10 to DNA. Former data on blood levels of Q10 and new data herein on blood levels of B6, measured as EDTA, in cancer patients established deficiencies of Q10 and B6 in cancer. This complete biochemistry relating to biosyntheses of Q10 and the DNA bases is a rationale for the therapy of cancer with Q10 and other entities in this biochemistry.


Natural products and their derivatives as cancer chemopreventive agents

Progress in Drug Research (Switzerland), 1997, 48/- (147- 171)

This review summarizes currently available data on the chemopreventive efficacies, proposed mechanisms of action and relationships between activities and structures of natural products like vitamin D, calcium, dehydroepidandrosterone, coenzyme Q10, celery seed oil, parsley leaf oil, sulforaphane, isoflavonoids, lignans, protease inhibitors, tea polyphenols, curcumin, and polysaccharides from Acanthopanax genus.


Thesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy

Biochemical and Biophysical Research Communications (USA), 1996, 224/2 (358-361)

In the human, coenzyme Q10 (vitamin Q10) is biosynthesized from tyrosine through a cascade of eight aromatic precursors. These precursors indispensably require eight vitamins, which are tetrahydrobiopterin, vitamins B6 C, B2, B12, folic acid, niacin, and pantothenic acid as their coenzymes. Three of these eight vitamins (the coenzyme B6 and the coenzymes niacin and folic acid) are indispensable in the biosynthesis of the four bases (thymidine, guanine, adenine, and cytosine) of DNA. One or more of the three vitamins required for DNA are known to cause abnormal pairing of the four bases, which can then result in mutations and the diversity of cancer. The coenzyme B6 required for the conversion of tyrosine to p- hydroxybenzoic acid, is the first coenzyme required in the cascade of precursors. A deficiency of the coenzyme B6 can cause dysfunctions, prior to the formation of vitamin Q10 to DNA. Former data on blood levels of Q10 and new data herein on blood levels of B6, measured as EDTA, in cancer patients established deficiencies of Q10 and B6 in cancer. This complete biochemistry relating to biosyntheses of Q10 and the DNA bases is a rationale for the therapy of cancer with Q10 and other entities in this biochemistry.


The effect of coenzyme Q10 on infarct size in a rabbit model of ischemia/reperfusion.

Birnbaum Y; Hale SL; Kloner RA. Heart Institute, Good Samaritan Hospital, Los Angeles, CA 90017, USA. Cardiovasc Res (NETHERLANDS) Nov 1996, 32 (5) p861-8

OBJECTIVE: Coenzyme Q10 has been found to enhance recovery of function after reperfusion in numerous experimental acute ischemia-reperfusion models. We assessed whether coenzyme Q10, administered intravenously either during or 1 h before ischemia, can limit infarct size in the rabbit.

METHODS: Anesthetized open-chest rabbits were subjected to 30 min of coronary artery occlusion and 4 h of reperfusion. In Protocol 1, 12 min after beginning of ischemia rabbits were randomized to intravenous infusion of 30 mg coenzyme Q10 (Eisai Co., Japan) (n = 10) or vehicle (n = 10). In Protocol 2, rabbits were randomized to 30 mg coenzyme Q10 (n = 6) or vehicle (n = 6) treatment 60 min before ischemia. Ischemic zone at risk (IZ) was assessed by blue dye and necrotic zone (NZ) by tetrazolium staining.

RESULTS: In both protocols, coenzyme Q10 did not alter heart rate, mean blood pressure, or regional myocardial blood flows in either the ischemic or non-ischemic zones during ischemia or reperfusion. No difference was found in IZ (as fraction of LV weight) (Protocol 1: 0.24 +/- 0.02 vs. 0.25 +/- 0.02; Protocol 2: 0.28 +/- 0.02 vs. 0.28 +/- 0.03, in the control vs. coenzyme Q10 groups, respectively). The NZ/IZ ratio was comparable between the groups in both protocols (Protocol 1: 0.22 +/- 0.04 vs. 0.26 +/- 0.04; Protocol 2: 0.21 +/- 0.06 vs. 0.30 +/- 0.06, in the control vs. coenzyme Q10 groups, respectively).

CONCLUSIONS: Coenzyme Q10, administered acutely either during or 60 min before myocardial ischemia, does not attenuate infarct size in the rabbit.


Protection by coenzyme Q10 of tissue reperfusion injury during abdominal aortic cross-clamping.

Chello M; Mastroroberto P; Romano R; Castaldo P; Bevacqua E; Marchese AR. Medical School of Catanzaro, Italy. J Cardiovasc Surg (Torino) (ITALY) Jun 1996, 37 (3) p229-35

PURPOSE: To evaluate the effect of coenzyme Q10 in reducing the skeletal muscle reperfusion injury following clamping and declamping the abdominal aorta.

METHODS: 30 patients undergoing elective vascular surgery for abdominal aortic aneurysm or obstructive aorto-iliac disease were randomly divided into two groups: patients in group I were treated with coenzyme Q10 (150 mg/day) for seven days before operation, and those in group II received a placebo. We studied the hemodynamic profile in each patient during clamping and declamping of the abdominal aorta. The plasma concentrations of thiobarbituric acid reactive substances (malondialdhehyde), conjugated dienes, creatine kinase and lactate dehydrogenase were measured in samples from both arterial and inferior vena cava sites. Serial sampling was performed after induction of anesthesia, 5 and 30 minutes after abdominal aortic cross clamping, 5 and 30 minutes after aortic cross-clamp removal.

RESULTS: The concentrations of malondialdehyde, conjugated dienes, creatine kinase and lactate dehydrogenase in patients who received CoQ10 were significantly lower than in the placebo group. Decrease of plasma malondialdehyde concentrations correlated positively (p < 0.01) with decrease of both creatine kinase and lactate dehydrogenase release in samples from the inferior vena cava. The hemodynamic profile during clamping and declamping the abdominal aorta was similar in both groups.

CONCLUSIONS: Our findings suggest that pre-treatment with coenzyme Q10 may play a protective role during routine vascular procedures requiring abdominal aortic cross clamping by attenuating the degree of peroxidative damage.


Isoprenoid (coQ10) biosynthesis in multiple sclerosis.

Acta Neurol Scand (DENMARK) Sep 1985, 72 (3) p328-35

Recently discovered metabolites in urine have suggested a defect of isoprenoid metabolism in multiple sclerosis. Lymphocyte HMG-CoA reductase was found unaffected however, and so was lymphocyte biosynthesis of geraniol, farnesol and squalene from mevalonolactone. The level of dolichol in white matter of an MS brain was similar to that of a control sample. Serum ubiquinone, on the other hand, was decreased in multiple sclerosis. Ubiquinone in serum was both age-dependent and related to serum cholesterol. Active as well as stable MS displayed a decreased level of serum ubiquinone, and a reduced ubiquinone-cholesterol ratio. These results are compatible with a deficient ubiquinone biosynthesis in multiple sclerosis.


Two successful double-blind trials with coenzyme Q10 (vitamin Q10) on muscular dystrophies and neurogenic atrophies.

Biochim Biophys Acta (NETHERLANDS) May 24 1995

Coenzyme Q10 (vitamin Q10) is biosynthesized in the human body and is functional in bioenergetics, anti-oxidation reactions, and in growth control, etc. It is indispensable to health and survival. The first double-blind trial was with twelve patients, ranging from 7-69 years of age, having diseases including the Duchenne, Becker, and the limb-girdle dystrophies, myotonic dystrophy. Charcot-Marie- Tooth disease, and the Welander disease. The control coenzyme Q10 (CoQ10) blood level was low and ranged from 0.5-0.84 microgram/ml. They were treated for three months with 100 mg daily of CoQ10 and a matching placebo. The second double-blind trial was similar with fifteen patients having the same categories of disease. Since cardiac disease is established to be associated with these muscle diseases, cardiac function was blindly monitored, and not one mistake was made in assigning CoQ10 and placebo to the patients in both trials. Definitely improved physical performance was recorded. In retrospect, a dosage of 100 mg was too low although effective and safe. Patients suffering from these muscle dystrophies and the like, should be treated with vitamin Q10 indefinitely.


Biochemical rationale and the cardiac response of patients with muscle disease to therapy with coenzyme Q10.

Proc Natl Acad Sci U S A (UNITED STATES) Jul 1985

Cardiac disease is commonly associated with virtually every form of muscular dystrophy and myopathy. A double- blind and open crossover trial on the oral administration of coenzyme Q10 (CoQ10) to 12 patients with progressive muscular dystrophies and neurogenic atrophies was conducted. These diseases included the Duchenne, Becker, and limb-girdle dystrophies, myotonic dystrophy, Charcot- Marie-Tooth disease, and Welander disease. The impaired cardiac function was noninvasively and extensively monitored by impedance cardiography. Solely by significant changeor no change in stroke volume and cardiac output, all 8 patients on blind CoQ10 and all 4 on blind placebo were correctly assigned (P less than 0.003). After the limited 3-month trial, improved physical well-being was observed for 4/8 treated patients and for 0/4 placebo patients; of the latter, 3/4 improved on CoQ10; 2/8 patients resigned before crossover; 5/6 on CoQ10 in crossover maintained improved cardiac function; 1/6 crossed over from CoQ10 to placebo relapsed. The rationale of this trial was based on known mitochondrial myopathies, which involve respiratory enzymes, the known presence of CoQ10 in respiration, and prior clinical data on CoQ10 and dystrophy. These results indicate that the impaired myocardial function of such patients with muscular disease may have some association with impaired function of skeletal muscle, both of which may be improved by CoQ10 therapy. The cardiac improvement was definitely positive. The improvement in well-being was subjective, but probably real. Likely, CoQ10 does not alter genetic defects but can benefit the sequelae of mitochondrial impairment from such defects. CoQ10 is the only known substance that offers a safe and improvedquality of life for such patients having muscle disease, and it is based on intrinsic bioenergetics.


[Some indices of energy metabolism in the tissues of mice with progressive muscular dystrophy under the action of ubiquinone]

Vopr Med Khim (USSR) May 1974, 20 (3) p276-84

Coenzyme Q10 (vitamin Q10) is biosynthesized in the human body and is functional in bioenergetics, anti-oxidation reactions, and in growth control, etc. It is indispensable to health and survival. The first double-blind trial was with twelve patients, ranging from 7-69 years of age, having diseases including the Duchenne, Becker, and the limb-girdle dystrophies, myotonic dystrophy. Charcot-Marie- Tooth disease, and the Welander disease. The control coenzyme Q10 (CoQ10) blood level was low and ranged from 0.5-0.84 microgram/ml. They were treated for three months with 100 mg daily of CoQ10 and a matching placebo. The second double-blind trial was similar with fifteen patients having the same categories of disease. Since cardiac disease is established to be associated with these muscle diseases, cardiac function was blindly monitored, and not one mistake was made in assigning CoQ10 and placebo to the patients in both trials. Definitely improved physical performance was recorded. In retrospect, a dosage of 100 mg was too low although effective and safe. Patients suffering from these muscle dystrophies and the like, should be treated with vitamin Q10 indefinitely.


The activities of coenzyme Q10 and vitamin B6 for immune responses.

Biochem Biophys Res Commun (UNITED STATES) May 28 1993, 193 (1)

Coenzyme Q10 (CoQ10) and vitamin B6 (pyridoxine) have been administered together and separately to three groups of human subjects. The blood levels of CoQ10 increased (p < 0.001) when CoQ10 and pyridoxine were administered together and when CoQ10 was given alone. The blood levels of IgG increased when CoQ10 and pyridoxine were administered together (p < 0.01) and when CoQ10 was administered alone (p < 0.05). The blood levels of T4- lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.01) and separately (p < 0.001). The ratio of T4/T8 lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.001) and separately (p < 0.05). These increases in IgG and T4-lymphocytes with CoQ10 and vitamin B6 are clinically important for trials on AIDS, other infectious diseases, and on cancer.


Research on coenzyme Q10 in clinical medicine and in immunomodulation.

Drugs Exp Clin Res (SWITZERLAND) 1985, 11 (8) p539-45

Coenzyme Q10 (CoQ10) is a redox component in the respiratory chain. CoQ10 is necessary for human life to exist; and a deficiency can be contributory to ill health and disease. A deficiency of CoQ10 in myocardial disease has been found and controlled therapeutic trials haveestablished CoQ10 as a major advance in the therapy of resistant myocardial failure. The cardiotoxicity of adriamycin, used in treatment modalities of cancer, is significantly reduced by CoQ10, apparently because the side-effects of adriamycin include inhibition of mitochondrial CoQ10 enzymes. Models of the immune system including phagocytic rate, circulating antibody level, neoplasia, viral and parasitic infections were used to demonstrate that CoQ10 is an immunomodulating agent. It was concluded that CoQ10, at the mitochondrial level, is essential for the optimal function of the immune system.


A modified determination of coenzyme Q10 in human blood and CoQ10 blood levels in diverse patients with allergies.

Biofactors (ENGLAND) Dec 1988, 1 (4) p303-6

Two situations required a modified determination of coenzyme Q10 (CoQ10) in human blood and organ tissue. Blood from patients with AIDS and cancer raised apprehensions about safety to an analyst, and the number of specimens for analysis is increasing enormously. A modified determination replaces silica gel-TLC with disposable Florisil columns, and steps were simplified to allow more analyses per unit time. Data from the modified determination are quantitatively compatible with data from older and tedious procedures. This determination was used for blood from 36 diverse patients with allergies. The mean CoQ10 blood level of these patients is not different from the mean level of so-called normal individuals, but approximately 40% (14/36) of these allergic patients had levels up to 0.65 micrograms/ml, which is the level of dying class IV cardiac patients. The biosynthesis of CoQ10 in human tissues is a complex process that requires several vitamins and micronutrients, so that countless vitamin-unsupplemented Americans may be deficient in CoQ10. The relationship of allergies to autoimmune mechanisms and immunity, and the established relationship of CoQ10 to immune states, may be a rationale for therapeutic trials of administering CoQ10 to patients with allergies who have low CoQ10 blood levels and are very likely deficient.


Biochemical deficiencies of coenzyme Q10 in HIV- infection and exploratory treatment.

Biochem Biophys Res Commun (UNITED STATES) Jun 16 1988, 153 (2) p888-96

AIDS patients (2 groups) had a blood deficiency (p less than 0.001) of coenzyme Q10 vs. 2 control groups. AIDS patients had a greater deficiency (p less than 0.01) than ARC patients. ARC patients had a deficiency (p less than 0.05) vs. control. HIV-infected patients had a deficiency (p less than 0.05) vs. control. The deficiency of CoQ10 increased with the increased severity of the disease, i.e., from HIV positive (no symptoms) to ARC (constitutional symptoms, no opportunistic infection or tumor) to AIDS (HIV infection, opportunistic infection and/or tumor). This deficiency, a decade of data on CoQ10 on the immune system, on IgG levels, on hematological activity constituted the rationale for treatment with CoQ10 of 7 patients with AIDS or ARC. One was lost to follow-up; one expired after stopping CoQ10; 5 survived, were symptomatically improved with no opportunistic infection after 4-7 months. In spite of poor compliance of 5/7 patients, the treatment was very encouraging and at times even striking.


Immunological senescence in mice and its reversal by coenzyme Q10.

Mech Ageing Dev (SWITZERLAND) Mar 1978, 7 (3) p189-97

A pronounced suppression of the humoral, hemolytic, primary immune response in old (22 months) mice was demonstrated as compared with this response in young (10 weeks) mice. The suppression is associated with a lower thymus weight: body weight ratio. In contrast, the ratio spleen weight: body weight and liver weight: body weight in 10 weeks and 22 months old mice remain almost constant. A single administration of coenzyme Q10--a non-toxic, non- specific stimulant of the host defense system--partly compensates the age-determined suppression of the humoral, immune response. This suppression probably results from an age-dependent imbalance of T cells: B cells ratio and a decline of their immunological responsiveness which is compensated by the administration of coenzyme Q10.


Treatment of essential hypertension with coenzyme Q10

Mol Aspects Med (ENGLAND) 1994, 15 Suppl pS265-72

A total of 109 patients with symptomatic essential hypertension presenting to a private cardiology practice were observed after the addition of CoQ10 (average dose, 225 mg/day by mouth) to their existing antihypertensive drug regimen. In 80 per cent of patients, the diagnosis of essential hypertension was established for a year or more prior to starting CoQ10 (average 9.2 years). Only one patient was dropped from analysis due to noncompliance. The dosage of CoQ10 was not fixed and was adjusted according to clinical response and blood CoQ10 levels. Our aim was to attain blood levels greater than 2.0 micrograms/ml (average 3.02 micrograms/ml on CoQ10). Patients were followed closely with frequent clinic visits to record blood pressure and clinical status and make necessary adjustments in drug therapy. Echocardiograms were obtained at baseline in 88% of patients and both at baseline and during treatment in 39% of patients. A definite and gradual improvement in functional status was observed with the concomitant need to gradually decrease antihypertensive drug therapy within the first one to six months. Thereafter, clinical status and cardiovascular drug requirements stabilized with a significantly improved systolic and diastolic blood pressure. Overall New York Heart Association (NYHA) functional class improved from a mean of 2.40 to 1.36 (P < 0.001) and 51% of patients came completely off of between one and three antihypertensive drugs at an average of 4.4 months after starting CoQ10. Only 3% of patients required the addition of one antihypertensive drug. In the 9.4% of patients with echocardiograms both before and during treatment, we observed a highly significant improvement in left ventricular wall thickness and diastolic function. (ABSTRACT TRUNCATED AT 250 WORDS)


Coenzyme Q10 in essential hypertension

Mol Aspects Med (ENGLAND) 1994, 15 Suppl ps257-63

This study was undertaken to clarify the mechanism of the antihypertensive effect of coenzyme Q10 (CoQ10). Twenty- six patients with essential arterial hypertension were treated with oral CoQ10, 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and high-density lipoprotein (HDL) cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period. At the end of the treatment, systolic blood pressure (SBP) decreased from 164.5 +/- 3.1 to 146.7 +/- 4.1 mmHg and diastolic blood pressure (DBP) decreased from 98.1 +/- 1.7 to 86.1 +/- 1.3 mmHg (P < 0.001). Plasma CoQ10 values increased from 0.64 +/- 0.1 microgram/ml to 1.61 +/- 0.3 micrograms/ml (P < 0.02). Serum total cholesterol decreased from 222.9 +/- 13 mg/dl to 213.3 +/- 12 mg/dl (P < 0.005) and serum HDL cholesterol increased from 41.1 +/- 1.5 mg/dl to 43.1 +/- 1.5 mg/dl (P < 0.01). In a first group of 10 patients serum sodium and potassium, plasma clinostatic and orthostatic renin activity, urinary aldosterone, 24-hour sodium and potassium were determined before and at the end of the 10-week period. In five of these patients peripheral resistances were evaluated with radionuclide angiocardiography. Total peripheral resistances were 2,283 +/- 88 dyne.s.cm-5 before treatment and 1,627 +/- 158 dyn.s.cm-5 after treatment (P < 0.02). Plasma renin activity, serum and urinary sodium and potassium, and urinary aldosterone did not change. In a second group of 11 patients, plasma endothelin, electrocardiogram, two-dimensional echocardiogram and 24- hour automatic blood pressure monitoring were determined. (ABSTRACT TRUNCATED AT 250 WORDS)


Usefulness of coenzyme Q10 in clinical cardiology: a long-term study

Mol Aspects Med (ENGLAND) 1994, 15 Suppl ps165-75

Over an eight year period (1985-1993), we treated 424 patients with various forms of cardiovascular disease by adding coenzyme Q10 (CoQ10) to their medical regimens. Doses of CoQ10 ranged from 75 to 600 mg/day by mouth (average 242 mg). Treatment was primarily guided by the patient's clinical response. In many instances, CoQ10 levels were employed with the aim of producing a whole blood level greater than or equal to 2.10 micrograms/ml (average 2.92 micrograms/ml, n = 297). Patients were followed for an average of 17.8 months, with a total accumulation of 632 patient years. Eleven patients were omitted from this study: 10 due to non-compliance and one who experienced nausea. Eighteen deaths occurred during the study period with 10 attributable to cardiac causes. Patients were divided into six diagnostic categories: ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), primary diastolic dysfunction (PDD), hypertension (HTN), mitral valve prolapse (MVP) and valvular heart disease (VHD). For the entire group and for each diagnostic category, we evaluated clinical response according to the New York Heart Association (NYHA) functional scale, and found significant improvement. Of 424 patients, 58 per cent improved by one NYHA class, 28% by two classes and 1.2% by three classes. A statistically significant improvement in myocardial function was documented using the following echocardiographic parameters: left ventricular wall thickness, mitral valve inflow slope and fractional shortening. Before treatment with CoQ10, most patients were taking from one to five cardiac medications. During this study, overallmedication requirements dropped considerably: 43% stopped between one and three drugs. Only 6% of the patients required the addition of one drug. No apparent side effects from CoQ10 treatment were noted other than a single case of transient nausea. In conclusion, CoQ10 is a safe and effective adjunctive treatment for a broad range of cardiovascular diseases, producing gratifying clinical responses while easing the medical and financial burden of multidrug therapy.


Influence of coenzyme Q-10 on the hypotensive effects of enalapril and nitrendipine in spontaneously hypertensive rats.

Pol J Pharmacol (POLAND) Sep-Oct 1994, 46 (5) p457-61

Administration of coenzyme Q-10 (10 mg/kg) once day for 4 weeks decreased the arterial blood pressure in SHR's. Enalapril and nitrendipine administered in a single dose caused significant decrease of blood pressure. Application of enalapril and nitrendipine to rats chronically pretreated with coenzyme Q-10 revealed, that the maximal hypotensive effect was not greater, but it lasted much (ca. 2-times) longer. Independently of mechanism of this interaction it may be suggested that the chronic administration of coenzyme Q-10 would create the possibility of significant decrease of the frequency of some antihypertensive drug administration.


Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment.

Clin Investig (GERMANY) 1993, 71 (8 Suppl) pS140-4

Symptoms of fatigue and activity impairment, atypical precordial pain, and cardiac arrhythmia frequently precede by years the development of congestive heart failure. Of 115 patients with these symptoms, 60 were diagnosed as having hypertensive cardiovascular disease, 27 mitral valve prolapse syndrome, and 28 chronic fatigue syndrome. These symptoms are common with diastolic dysfunction, and diastolic function is energy dependent. All patients had blood pressure, clinical status, coenzyme Q10 (CoQ10) blood levels and echocardiographic measurement of diastolic function, systolic function, and myocardial thickness recorded before and after CoQ10 replacement. At control, 63 patients were functional class III and 54 class II; all showed diastolic dysfunction; the mean CoQ10 blood level was 0.855 micrograms/ml; 65%, 15%, and 7% showed significant myocardial hypertrophy, and 87%, 30%, and 11% had elevated blood pressure readings in hypertensive disease, mitral valve prolapse and chronic fatigue syndrome respectively. Except for higher blood pressure levels and more myocardial thickening in the hypertensive patients, there was little difference between the three groups. CoQ10 administration resulted in improvement in all; reduction in high blood pressure in 80%, and improvement in diastolic function in all patients with follow-up echocardiograms to date; a reduction in myocardial thickness in 53% of hypertensives and 36% of the combined prolapse and fatigue syndrome groups; and a reduced fractional shortening in those high at control and an increase in those initially low. (ABSTRACT TRUNCATED AT 250 WORDS)


Muscle fibre types, ubiquinone content and exercise capacity in hypertension and effort angina.

Ann Med (FINLAND) Aug 1991, 23 (3) p339-44

The composition of skeletal muscle fibre expressed as a percentage of slow twitch (ST), type I or red and fast twitch (FT), type II or white were determined in patients with hypertension (HT) or with severe ischaemic heart disease (IHD) and compared to age matched controls. Similarly, exercise capacity expressed as the cycle intensity eliciting A blood lactate concentration corresponding to 2.0 mmol x 1-1 were compared with healthy controls. Both patient groups had a higher percentage of FT fibres with relatively lower exercise capacities than their controls. The exercise capacities were reduced even when the relationship of decreased capacity with the percentage of increased FT was considered. There was an increase IHD but not in HT in patients with fibre subgroup FTc, which most probably reflected fibre trauma. Both patient groups were low in the skeletal muscle mitochondrial electron carrier and unspecific antioxidant ubiquinone, coenzyme Q10 or CoQ10. Patients with IHD but not HT showed, however, a faster fall in the ratio CoQ10 over ST% the higher the percentage value of ST. The ratio reflects the antioxidant activity related to CoQ10 in the fibre hosting most of the oxidative metabolism. A low ratio indicates a risk of metabolic lesion and cell trauma. This could explain fibre plasticity and offer an alternative cause to heredity in elucidating in deviating muscle fibre composition in patients with HT and IHD.


Effect of coenzyme Q10 on structural alterations in the renal membrane of stroke-prone spontaneously hypertensive rats

Biochem Med Metab Biol (UNITED STATES) Apr 1991, 45 (2) p216-26

To test the hypothesis that structural abnormalities exist in the kidney membrane of spontaneously hypertensive rats, we examined the effect of long-term administration of coenzyme Q10 on membrane lipid alterations in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP). As compared with normotensive Wistar-Kyoto rats, renal membrane phospholipids, especially phosphatidylcholine and phosphatidylethanolamine, decreased and renal phospholipase A2 activity was enhanced with age in untreated SHRSP. Treatment with coenzyme Q10 attenuated the elevation of blood pressure, the membranous phospholipid degradation, and the enhanced phospholipase A2 activity. These results suggest that one factor contributing to the progress of hypertension is a structural membrane abnormality that alters the physical and functional properties of the cell membrane, and coenzyme Q10 might protect the renal membrane from damage due to hypertension in SHRSP.


Co-enzyme Q10: a new drug for cardiovascular disease

J Clin Pharmacol (UNITED STATES) Jul 1990, 30 (7) p596-608

Co-enzyme Q10 (ubiquinone) is a naturally occurring substance which has properties potentially beneficial for preventing cellular damage during myocardialischemia and reperfusion. It plays a role in oxidative phosphorylation and has membrane stabilizing activity. The substance has been used in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure. Its clinical importance is now being established in clinical trails worldwide. (133 Refs.)


Coenzyme Q10: a new drug for myocardial ischemia?

Med Clin North Am (UNITED STATES) Jan 1988, 72 (1) p243-58

A biochemical rationale for using CoQ in treating certain cardiovascular diseases has been established. CoQ subserves an endogenous function as an essential cofactor in several metabolic pathways, particularly oxidative respiration. As an exogenous source in supraphysiologic doses, CoQ may have pharmacologic effects that are beneficial to tissues rendered ischemic and then reperfused. Its mechanism of action appears to be that of a free radical scavenger and/or direct membrane stabilizer. Initial clinical studies performed abroad and in the United States indicate that CoQ may be effective in treating certain patients with ischemic heart disease, congestive heart failure, toxin-induced cardiotoxicity, and possibly hypertension. The most intriguing property of CoQ is its potential to protect and preserve ischemic myocardium during surgery. Currently, CoQ is still considered an experimental agent and only further studies will determine whether it will be useful therapy for human cardiovascular disease states. (105 Refs.)


Clinical study of cardiac arrhythmias using a 24-hour continuous electrocardiographic recorder (5th report)-- antiarrhythmic action of coenzyme Q10 in diabetics.

Tohoku J Exp Med (JAPAN) Dec 1983, 141 Suppl p453-63

An investigation was undertaken to evaluate the antiarrhythmic effect of CoQ10 on VPBs using the Holter ECG, in 27 patients with no clinical findings of organic cardiopathies. As a result, the effect of CoQ10 on VPBs was considered beneficial in 6 (22%) of 27 cases, consisting of 1 patient with hypertension and 5 patients with DM. Even in the remaining 2 patients with DM, the frequency of VPBs was reduced by 50% or more during treatment with CoQ10. The mean reduction of VPBs frequency in the 5 responders plus these 2 patients with DM was 85.7%. These findings suggest that CoQ10 exhibits an effective antiarrhythmic action not merely on organic heart disease but also on VPBs supervening on DM.


Bioenergetics in clinical medicine. XVI. Reduction of hypertension in patients by therapy with coenzyme Q10.

Res Commun Chem Pathol Pharmacol (UNITED STATES) Jan 1981, 31 (1) p129-40

Six untreated hypertensive patients and ten on therapy, but having elevated blood pressures, were treated with coenzyme Q10 (CoQ10); 14/16 patients showed reductions (p less than 0.05-less than 0.001) in systolic pressures; 11/16 showed reductions (p less than 0.05-less than 0.001) in diastolic pressure; 9/10 showed reductions of elevated pressures to a normal range. By impedance cardiography and electrocardiography, there were no changes in cardiac outputs, stroke volumes and Heather Indices except for a few patients with changes of doubtful biological significance. 3/16 patients had exceptionally low basal specific activities of the succinate dehydrogenase- coenzyme Q10 reductase in blood which increased to a normal range on treatment. A greater deficiency of CoQ10 in the vascular system than inblood is likely. We consider that (1) the mechanism of reduction of elevated blood pressures by CoQ10 is based upon normalization or autoregulation of peripheral resistance rather than cardiac regulation, and (2) that the therapeutic activity of CoQ10 is not pharmacodynamic, but results from a translational increase in levels of CoQ10-enzymes in vascular tissue during ca. 4-12 weeks.


Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors.

Res Commun Chem Pathol Pharmacol (UNITED STATES) May 1977, 17 (1) p157-64

Adrenergic blockers for beta-receptors were studied for inhibition of mitochrondrial CoQ10-enzymes. These enzymes are indispensable for the bioenegetics of the myocardium. Propranolol is frequently used to treat hypertension; in some patients, it depresses myocardial function as an adverse reaction. This side effect may be related to the inhibition by propranolol of CoQ10-enzymes of the myocardium. Timolol showed negligible inhibition of the CoQ10-enzyme, NADH-oxidase. Metoprolol was less inhibitory than propranolol. Five alprenolols showed inhibition which approached that of propranolol. The 1-isomer of alprenolol showed weak inhibition of another CoQ10-enzyme, succinoxidase, but the other beta-blockers were essentially non-inhibitory to this enzyme. The drug of choice is timolol, based on negligible inhibition of these bioenergetic enzymes of the heart, which correlates with its pharmacologically low cardiac depressant effects.


Bioenergetics in clinical medicine. VIII. Adminstration of coenzyme Q10 to patients with essential hypertension.

Res Commun Chem Pathol Pharmacol (UNITED STATES) Aug 1976, 14 (4) p721-7

Coenzyme Q10 has been administered to five patients having essential hypertension and deficiencies of activity of succinate dehydrogenase-co-enzyme Q10 reductase in leucocyte preparations ranging from 20-40%. For a 74-year old male, the systolic pressure was reduced (p less than 0.001), the diastolic pressure was reduced (p less than 0.05), the specific activity of the coenzyme Q10-enzyme was increased (p less than 0.001), and the deficiency of coenzyme Q10 activity was negated (p less than 0.01). Four patients receiving CoQ10 for 3-5 months showed reductions (p less than 0.05 to p less than 0.001) of diastolic pressure, and 3 of these 4 showed reductions (p less than 0.05 to p less than 0.01) of diastolic pressure. Initial deficiencies of enzyme activity were reduced (p less than 0.01 to 0.05) in two patients. Three other patients did not show the high level of deficiency on treatment as initially observed. These effects of CoQ10 on the reduction of systolic and diastolic blood pressures, increase in CoQ10-enzyme activity, and reduction of CoQ10- deficiency are presumably due to improved bioenergetics through correction of a deficiency of coenzyme Q10.


Bioenergetics in clinical medicine. III. Inhibition of coenzyme Q10-enzymes by clinically used anti-hypertensive drugs

Res Commun Chem Pathol Pharmacol (UNITED STATES) Nov 1975, 12 (3) p533-40

Background data revealed that some American and Japanese patients with essential hypertension, including many who were not being treated with any anti-hypertensive drug, had a deficiency of coenzyme Q10. Eight clinically used anti-hypertensive drugs have now been tested for inhibition of two mitochondrial coenzyme Q10-enzymes of heart tissue, succinoxidase and NADH-oxidase. Diazoxide and propranolol significantly inhibited the CoQ10- succinoxidase and CoQ10-NADH-oxidase, respectively. Metoprolol did not inhibit succinoxidase, and was one- fourth as active as propranolol for inhibition of NADH- oxidase. Hydrochlorothiazide, hydralazine, ans clonidine also inhibited CoQ10-NADH-oxidase. Reserpine did not inhibit either CoQ10-enzyme, and methyldopa was a very eak inhibitor of succinoxidase. The internationally recognized clinical side-effects of propranolol may be due, in part, to inhibition of CoQ10-enzymes which are indispensable in the bioenergetics of cardiac function. A pre-existing deficiency of coenzyme Q10 in the myocardium of hypertensive patients could be augmented by subsequent treatment with propranolol, possibly to the life- threatening state described by others.


Bioenergetics in clinical medicine. Studies on coenzyme Q10 and essential hypertension.

Res Commun Chem Pathol Pharmacol (UNITED STATES) Jun 1975, 11 (2) p273-88

The specific activities (S.A.) of the succinate dehydrogenase-coenzyme Q10 (CoQ10) reductase of a control group of 65 Japanese adults and 59 patients having essential hypertension were determined. The mean S.A. of the hypertensive group was significantly lower (p less than 0.001) and the mean % deficiency of enzyme activity was significantly higher (p less than 0.001) than the values for the control group. These data on Japanese in Osaka agree with data on Americans in Dallas. Some patients showed no CoQ10-deficiency, and others showed definite deficiencies. Emphasizing the CoQ10-enzyme for patient selection, CoQ10 was administered to hypertensive patients. Four individuals showed significant but partial reductions of blood pressure. Monitoring the CoQ10-enzyme before, during, and after administration of CoQ10 indicated responses. The maintenance of high blood pressure could be primarily due to contraction of the arterial wall. Contraction or relaxation of an arterial wall is dependent upon bioenergetics, which also provide the energy for biosynthesis of angiotensin II, renin, aldosterone, and the energy for sodium and potassium transport. A clinical benefit from administration of CoQ10 to patients with essential hypertension could be based upon correcting a deficiency in bioenergetics, and point to possible combination treatments with a form of CoQ and anti-hypertensive drugs.


Plasma ubiquinol-10 is decreased in patients with hyperlipidaemia

Atherosclerosis (Ireland), 1997, 129/1 (119-126)

Ubiquinol-10, the reduced form of ubiquinone-10 (coenzyme Q10), is a potent lipophilic antioxidant present in nearly all human tissues. The exceptional oxidative lability of ubiquinol-10 implies that it may represent a sensitive index of oxidative stress. The present study was undertaken to assess the hypothesis that the level of ubiquinol-10 in human plasma can discriminate between healthy subjects and patients who are expected to be subjected to an increased oxidative stress in vivo. Using a newly developed method, we measured plasma ubiquinol-10 in 38 hyperlipidaemic patients with and without further complications, such as coronary heart disease, hypertension, or liver disease, and in 30 healthy subjects. The oxidizability of plasma samples obtained from hyperlipidaemic patients was found to be increased in comparison with control subjects, suggesting that the patients were subjected to a higher oxidative stress in vivo than the controls. Plasma ubiquinol-10, expressed as a percentage of total ubiquinol-10 + ubiquinone-10 or normalized to plasma lipids, was lower in the patients than in controls (P = 0.001 and 0.008, respectively). The proportion of ubiquinol-10 decreased in the order young controls aged controls hyperlipidaemic patients without complications hyperlipidaemic patients with complications (P = 0.003). A negative correlation was found between the proportion of ubiquinol-10 and plasma triglycerides. The hyperlipidaemic patients with hypertension had a lower proportion of ubiquinol-10 than subjects without. When the study population was divided into smokers and non-smokers, plasma ubiquinol-10 was found to be reduced amongst smokers, independently of whether it was expressed as a percentage of total ubiquinol-10 + ubiquinone-10 (P = 0.006) or normalized to plasma lipids (P = 0.009). These data suggest that the level of ubiquinol-10 in human plasma may represent a sensitive index of oxidative stress in vivo especially indicative of early oxidative damage. Measuring plasma ubiquinol-10 can be proposed as a practical approach to assess oxidative stress in humans.


Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex

BIOCHEM. BIOPHYS. RES. COMMUN. (USA), 1991, 176/2 (786-791)

Coenzyme Q10 (CoQ10) is indispensable to biochemical mechanisms of bioenergetics, and it has a non-specific role as an antioxidant. CoQ10 has shown a hematological activity for the human and has shown an influence on the host defense system. The T4/T8 ratios of lymphocytes are known to be low in patients with AIDS, ARC and malignancies. Our two patients with ARC have survived four- five years without any symptoms of adenopathy or infection on continuous treatment with CoQ10. We have newly found that 14 ordinary subjects responded to CoQ10 by increases in the T4/T8 ratios and an increase in blood levels of CoQ10; both by p < 0.001. This knowledge and survival of two ARC patients for four-five years on CoQ10 without symptoms, and new data on increasing ratios of T4/T8 lymphocytes in the human by treatment with CoQ10 constitute a rationale for new double blind clinical trials on treating patients with AIDS, ARC and diverse malignancies with CoQ10.


The clinical and hemodynamic effects of Coenzyme Q10 in congestive cardiomyopathy

American Journal of Therapeutics (USA), 1997, 4/2-3 (66-72)

Despite major advances in treatment congestive heart failure (CHF) is still one of the major causes of morbidity and mortality. Coenzyme Q10 is a naturally occurring substance that has antioxidant and membrane stabilizing properties. Administration of coenzyme Q10 in conjunction with standard medical therapy has been reported to augment myocardial kinetics, increase cardiac output, elevate the ischemic threshold, and enhance functional capacity in patients with congestive heart failure. The aim of this study was to investigate some of these claims. Seventeen patients (mean New York Heart Association functional class 3.0 plus or minus 0.4) were enrolled in an open-label study. After 4 months of coenzyme Q10 therapy, functional class improved 20% (3.0 plus or minus 0.4 to 2.4 plus or minus 0.6, p < 0.001) and there was a 27% improvement in mean CHF score (2.8 plus or minus 0.4 to 2.2 plus or minus 0.4, p < 0.001). Percent change in the resting variables included the following: left ventricular ejection fraction (LVEF), +34.8%; cardiac output, +15.7%; stroke volume index, +18.9%; end- diastolic volume area, -8.4%; systolic blood pressure (SBP), -4.4%; and E (max), (SBP + end-systolic volume index (ESVI)) +11.7%. MV (O2) decreased by 5.3% (31.9 plus or minus 2.6 to 30.2 plus or minus 2.4, p = NS). Therapy with coenzyme Q10 was associated with a mean 25.4% increase in exercise duration and a 14.3% increase in workload. Percent changes after therapy include the following: exercise LVEF, +24.6%; cardiac output, +19.1%; stroke volume index, +13.2%; heart rate, +6.5%; SBP, - 4.3%; SBP + ESVI, +18.6%; end-diastolic volume (EDV) area, -6.0%; MV (O2), -7.0%; and ventricular compliance (% Delta SV + EDV) improved 100%. In


Summary

, coenzyme Q10 therapy is associated with significant functional, clinical, and hemodynamic improvements within the context of an extremely favorable benefit-to-risk ratio. Coenzyme Q10 enhances cardiac output by exerting a positive inotropic effect upon the myocardium as well as mild vasodilatation.


NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings.

J Inherit Metab Dis (NETHERLANDS) 1996, 19 (5) p675-86

Twelve patient cell lines with biochemically proven complex I deficiency were compared for clinical presentation and outcome, together with their sensitivity to galactose and menadione toxicity. Each patient had elevated lactate to pyruvate ratios demonstrable in fibroblast cultures. Each patient also had decreased rotenone-sensitive NADH-cytochrome c reductase (complexes I and III) with normal succinate cytochrome c reductase (complexes II and III) and cytochrome oxidase (complex IV) activity in cultured skin fibroblasts, indicating a deficient NADH-coenzyme Q reductase (complex I) activity. The patients fell into five categories: severe neonatal lactic acidosis; Leigh disease; cardiomyopathy and cataracts; hepatopathy and tubulopathy; and mild symptoms with lactic acidaemia. Cell lines from 4 out of the 12 patients were susceptible to both galactose and menadione toxicity and 3 of these also displayed low levels of ATP synthesis in digitonin-permeabilized skin fibroblasts from a number of substrates. This study highlights the heterogeneity of complex I deficiency at the clinical and biochemical level.


Effect of protection and repair of injury of mitochondrial membrane-phospholipid on prognosis in patients with dilated cardiomyopathy.

Blood Press Suppl (NORWAY) 1996, 3 p53-5

We have already proved that the mitochondrial membrane- phospholipid (MMP) injury changes of peripheral lymphocytes in patients with heart failure can be used as an injury indicator of myocardia, and are related to the long-term prognosis. In the present study, MMP localization of the peripheral lymphocytes was performed by modified Demer's tricomplex flocculation method, and we compared the changes, after classification, between the pre-treatment and the 12-week post-treatment, of coenzyme Q10 (Co.Q10) and captopril in 61 hospitalized patients with dilated cardiomyopathy (DCM). They were followed up for 16.1 +/- 7.8 months (mean). The results showed that compared with the placebo, Co.Q10 and captopril could significantly protect against and repair MMP injury and improve the heart function of patients with DCM after 12 weeks, and the 2-year survival rate rose significantly by 72.7% for Co.Q10, and 64.0% for captopril, vs 24.7% for placebo. As for Longrank test, X2 equals 4.660 and 6.318, respectively, with both p < 0.05. The aforementioned results indicate that MMP injury of peripheral lymphocytes can predict the prognosis of the patients with DCM, thus the protection and repairment of MMP injury can improve the life-quality and prolong the life-span of thepatients.


[Therapeutic effects of coenzyme Q10 on dilated cardiomyopathy: assessment by 123I-BMIPP myocardial single photon emission computed tomography (SPECT): a multicenter trial in Osaka University Medical School Group]

Kaku Igaku (JAPAN) Jan 1996, 33 (1) p27-32

To evaluate therapeutic effects of Cenzyme Q10 (CoQ10), 15 patients with dilated cardiomyopathy were investigated by 123I-BMIPP myocardial single photon emission computed tomography (SPECT). The BMIPP defect score was determined semiquantitatively by using representative short and long axial SPECT images. Mean BMIPP defect score with CoQ10 treatment was significantly low, 7.7 +/- 6.1 compared to 12.7 +/- 7.4 without CoQ10 treatment. On the other hand, in 8 patients of dilated cardiomyopathy, % fractional shortening using echocardiography was not different before and after CoQ10 treatment. In conclusion, 123I-BMIPP myocardial SPECT was proved to be sensitive to evaluate the therapeutic effects of CoQ10, which improve myocardial mitochondrial function, in the cases of dilated cardiomyopathy.


Italian multicenter study on the safety and efficacy of COENZYME Q10 as adjunctive therapy in heart failure.

Mol Aspects Med (ENGLAND) 1994, 15 Suppl ps287-94

Digitalis, diuretics and vasodilators are considered the standard therapy for patients with congestive heart failure, for which treatment is tailored according to the severity of the syndrome and the patient profile. Apart from the clinical seriousness, heart failure is always characterized by an energy depletion status, as indicated by low intramyocardial ATP and coenzyme Q10 levels. We investigated safety and clinical efficacy of COENZYME Q10 (CoQ10) adjunctive treatment in congestive heart failure that had been diagnosed at least 6 months previously and treated with standard therapy. A total of 2664 patients in NYHA classes II and III were enrolled in this open noncomparative 3-month postmarketing study in 173 Italian centers. The daily dosage of CoQ10 was 50-150 mg orally, with the majority of patients (78%) receiving 100 mg/day. Clinical and laboratory parameters were evaluated at the entry into the study and on day 90; the assessment of clinical signs and symptoms was made using from two-to seven-point scales. The results show a low incidence of side effects: 38 adverse effects were reported in 36 patients (1.5%) of which 22 events were considered as correlated to the test treatment. After three months of test treatment the proportions of patients with improvement in clinical signs and symptoms were as follows: cyanosis 78.1%, oedema 78.6%, pulmonary rales77.8%, enlargement of liver area 49.3%, jugular reflux 71.81%, dyspnoea 52.7%, palpitations 75.4%, sweating 79.8%, subjective arrhytmia 63.4%, insomnia 662.8%, vertigo 73.1% and nocturia 53.6%. Moreover we observed a contemporary improvement of at least three symptoms in 54% of patients; this could be interpreted as an index of improved quality of life.

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