Whole Body Health Sale

COENZYME Q10



Table of Contents
image Refractory congestive heart failure successfully managed with high dose coenzyme Q10 administration
image Effects of oral supplementation of coenzyme Q10 on 31P-NMR detected skeletal muscle energy metabolism in middle-aged post-polio subjects and normal volunteers
image The effect of coenzyme Q10 on the exercise performance of cross-country skiers
image T-2 toxin-induced DNA damage in mouse livers: The effect of pretreatment with coenzyme Q10 and alpha-tocopherol
image The mechanisms of coenzyme Q10 as therapy for myocardial ischemia reperfusion injury
image Usefulness of coenzyme Q10 in clinical cardiology: a long-term study
image Perspectives on therapy of cardiovascular diseases with coenzyme Q10 (ubiquinone)
image Coenzyme Q10: a new drug for cardiovascular disease
image Treatment of essential hypertension with coenzyme Q10
image Coenzyme Q10 in essential hypertension
image The effect of coenzyme Q10 on infarct size in a rabbit model of ischemia/reperfusion.
image Protection by coenzyme Q10 of tissue reperfusion injury during abdominal aortic cross-clamping.
image Isoprenoid (coQ10) biosynthesis in multiple sclerosis.
image Two successful double-blind trials with coenzyme Q10 (vitamin Q10) on muscular dystrophies and neurogenic atrophies.
image Biochemical rationale and the cardiac response of patients with muscle disease to therapy with coenzyme Q10.
image [Some indices of energy metabolism in the tissues of mice with progressive muscular dystrophy under the action of ubiquinone]
image The activities of coenzyme Q10 and vitamin B6 for immune responses.
image Research on coenzyme Q10 in clinical medicine and in immunomodulation.
image A modified determination of coenzyme Q10 in human blood and CoQ10 blood levels in diverse patients with allergies.
image Biochemical deficiencies of coenzyme Q10 in HIV-infection and exploratory treatment.
image Immunological senescence in mice and its reversal by coenzyme Q10.
image Treatment of essential hypertension with coenzyme Q10
image Coenzyme Q10 in essential hypertension
image Usefulness of coenzyme Q10 in clinical cardiology: a long-term study
image Influence of coenzyme Q-10 on the hypotensive effects of enalapril and nitrendipine in spontaneously hypertensive rats.
image Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment.
image Muscle fibre types, ubiquinone content and exercise capacity in hypertension and effort angina.
image Effect of coenzyme Q10 on structural alterations in the renal membrane of stroke-prone spontaneously hypertensive rats
image Co-enzyme Q10: a new drug for cardiovascular disease
image Coenzyme Q10: a new drug for myocardial ischemia?
image Clinical study of cardiac arrhythmias using a 24-hour continuous electrocardiographic recorder (5th report)--antiarrhythmic action of coenzyme Q10 in diabetics.
image Bioenergetics in clinical medicine. XVI. Reduction of hypertension in patients by therapy with coenzyme Q10.
image Prospects for nutritional control of hypertension
image Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors.
image Bioenergetics in clinical medicine. VIII. Adminstration of coenzyme Q10 to patients with essential hypertension.
image Bioenergetics in clinical medicine. III. Inhibition of coenzyme Q10-enzymes by clinically used anti-hypertensive drugs
image Bioenergetics in clinical medicine. Studies on coenzyme Q10 and essential hypertension.
image Plasma ubiquinol-10 is decreased in patients with hyperlipidaemia
image Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex
image The clinical and hemodynamic effects of Coenzyme Q10 in congestive cardiomyopathy
image Fish oil and other nutritional adjuvants for treatment of congestive heart failure
image NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings.
image Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase.
image Effect of protection and repair of injury of mitochondrial membrane-phospholipid on prognosis in patients with dilated cardiomyopathy.
image [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]
image Italian multicenter study on the safety and efficacy of COENZYME Q10 as adjunctive therapy in heart failure.
image [Coenzyme Q10 (ubiquinone) in the treatment of heart failure. Are any positive effects documented?]
image Italian multicenter study on the safety and efficacy of COENZYME Q10 as adjunctive therapy in heart failure (interim analysis). The CoQ10 Drug Surveillance Investigators.
image Effect of COENZYME Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study.
image Role of metabolic therapy in cardiovascular disease.
image Cardiac performance and COENZYME Q10 in thyroid disorders
image A clinical study of the effect of COENZYME Q on congestive heart failure.
image Effects of coenzyme Q10 administration on pulmonary function and exercise performance in patients with chronic lung diseases.
image Unrecognized pandemic subclinical diabetes of the affluent nations: Causes, cost and prevention
image [Effect of biological membrane stabilizing drugs (coenzyme Q10, dextran sulfate and reduced glutathione) on adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice]
image Coenzyme Q10, plasma membrane oxidase and growth control.
image Protective effects of various drugs on adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice and rats.
image Tissue concentration of doxorubicin (adriamycin) in mouse pretreated with alpha-tocopherol or coenzyme Q10.
image [Electrocardiogram analysis of adriamycin cardiotoxicity in 160 cases]
image Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases.
image Apparent partial remission of breast cancer in 'high risk' patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10.
image Effects of isoprenoids (coQ10) on growth of normal human mammary epithelial cells and breast cancer cells in vitro.
image Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10.
image An expanded concept of "insurance" supplementation--broad-spectrum protection from cardiovascular disease.
image Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure (interim analysis)
image [Effects of 2,3-dimethoxy-5-methyl-6-(10'-hydroxydecyl)-1,4-benzoquinone (CV-2619) on adriamycin-induced ECG abnormalities and myocardial energy metabolism in spontaneously hypertensive rats]
image Effects of short-term supplementation with coenzyme Q10 on myocardial protection during cardiac operations
image Myocardial preservation by therapy with coenzyme Q10 during heart surgery
image Effect of CoQ10 on myocardial ischemia/reperfusion injury in the isolated rat heart
image Measurement of the ratio between the reduced and oxidized forms of coenzyme Q10 in human plasma as a possible marker of oxidative stress.
image The role of free radicals in disease
image Coenzyme Q10 and coronary artery disease
image Isoprenoids (coQ10) in aging and neurodegeneration.
image Muscle biopsy in Alzheimer's disease: Morphological and biochemical findings
image 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
image Natural products and their derivatives as cancer chemopreventive agents
image Thesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy
image Anti-atherogenic effect of coenzyme Q10 in apolipoprotein E gene knockout mice.
image Coenzyme Q10 enrichment decreases oxidative DNA damage in human lymphocytes.
image A role for reduced coenzyme Q in atherosclerosis?
image Oxidation and antioxidation of human low-density lipoprotein and plasma exposed to 3-morpholinosydnonimine and reagent peroxynitrite.
image Oxidation of high density lipoproteins. I. Formation of methionine sulfoxide in apolipoproteins AI and AII is an early event that accompanies lipid peroxidation and can be enhanced by alpha-tocopherol.
image Oxidation of free fatty acids in low density lipoprotein by 15-lipoxygenase stimulates nonenzymic, alpha-tocopherol-mediated peroxidation of cholesteryl esters.
image Alpha-tocopheryl hydroquinone is an efficient multifunctional inhibitor of radical-initiated oxidation of low density lipoprotein lipids.
image Plasma and LDL levels of major lipophilic antioxidants are similar in patients with advanced atherosclerosis and age-matched controls.
image Inhibition of LDL oxidation by ubiquinol-10. A protective mechanism for coenzyme Q in atherogenesis?
image 3-Hydroxyanthranilic acid is an efficient, cell-derived co-antioxidant for alpha-tocopherol, inhibiting human low density lipoprotein and plasma lipid peroxidation.
image Radical-initiated lipid peroxidation in low density lipoproteins: insights obtained from kinetic modeling.
image Cosupplementation with coenzyme Q prevents the prooxidant effect of alpha-tocopherol and increases the resistance of LDL to transition metal-dependent oxidation initiation.
image Coantioxidants make alpha-tocopherol an efficient antioxidant for low-density lipoprotein.
image Inverse deuterium kinetic isotope effect for peroxidation in human low-density lipoprotein (LDL): a simple test for tocopherol-mediated peroxidation of LDL lipids.
image Prevention of tocopherol-mediated peroxidation in ubiquinol-10-free human low density lipoprotein.
image Radical-mediated oxidation of isolated human very-low-density lipoprotein.
image Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation.
image The oxidation of blood plasma and low density lipoprotein components by chemically generated singlet oxygen.
image Extracellular reduction of ubiquinone-1 and -10 by human Hep G2 and blood cells.
image Circulating lipid hydroperoxide levels in human hyperhomocysteinemia. Relevance to development of arteriosclerosis.
image Comparative antioxidant activity of tocotrienols and other natural lipid-soluble antioxidants in a homogeneous system, and in rat and human lipoproteins.
image Oxidation of low-density lipoprotein with hypochlorite causes transformation of the lipoprotein into a high-uptake form for macrophages.
image Autoxidation of lipids and antioxidation by alpha-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids: unrecognized consequences of lipid particle size as exemplified by oxidation of human low density lipoprotein.
image Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant.
image High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors.
image The participation of nitric oxide in cell free- and its restriction of macrophage-mediated oxidation of low-density lipoprotein.
image Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation.
image Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol.
image Oxidative stress and abnormal cholesterol metabolism in patients with adult respiratory distress syndrome.

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Refractory congestive heart failure successfully managed with high dose coenzyme Q10 administration

Sinatra S.T., Molecular Aspects of Medicine (United Kingdom), 1997, 18/SUPPL. (S299-S305)

Coenzyme Q10 (CoQ10) is a critical adjuvant therapy for patients with congestive heart failure (CHF), even when traditional medical therapy is successful. Adjunctive therapy with Q10 may allow for a reduction of other pharmacological therapies, improvement in quality of life, and a decrease in the incidence of cardiac complications in congestive heart failure.

However, dosing, clinical application, bioavailability and dissolution of CoQ10 deserve careful scrutiny whenever employing the nutrient. The assessment of blood levels in 'therapeutic failures' appears warranted.



Effects of oral supplementation of coenzyme Q10 on 31P-NMR detected skeletal muscle energy metabolism in middle-aged post-polio subjects and normal volunteers

Mizuno M.; Quistorff B.; Theorell H.; Theorell M.; Chance B.,
Molecular Aspects of Medicine (United Kingdom), 1997, 18/SUPPL. (S291-S298)

The effects of oral supplementation of 100 mg coenzyme Q10 (CoQ10) for 6 months on muscle energy metabolism during exercise and recovery were evaluated in middle-aged post-polio (n=3) and healthy subjects (n=4) by the use of phosphorus-31 nuclear magnetic resonance spectroscopy. The metabolic response to isometric plantar flexion at 60% of maximal voluntary contraction force (MVC) for 1.5 minutes was determined in gastrocnemius muscles before, after 3 months and 6 months of CoQ10 supplementation.

The MVC of plantar flexion was unchanged following CoQ10 supplementation. The resting P(i)/PCr ratio in gastrocnemius muscles of all subjects decreased after 3 months and 6 months CoQ10 (P < 0.05). The post-polio individuals showed a progressive decrease in this ratio, while less pronounced changes were observed in the control subjects.

Similarly, the post-polio individuals showed a lower P(i)/PCr ratio at the end of 60% MVC in both 3 month and 6 month CoQ10, whereas no change in the ratio was observed in the control subjects. A less pronounced decrease in muscle pH was observed at the end of 60% MVC in both 3 month and 6 month CoQ10 in the post-polio individuals, but not in the control subjects. No systematic difference in end-exercise ATP was observed between the three phases in both groups. The half-time of recovery for PCr decreased in all subjects after 6 months of CoQ10 supplementation (P < 0.05).

The results suggest that CoQ10 supplementation affects muscle energy metabolism in post-polio individuals to a greater extent than in control subjects. The mechanism for this effect is not clear, but may involve an effect of CoQ10 on peripheral circulation in the calf muscles, its action in mitochondrial oxidative phosphorylation and/or its antioxidant potential.



The effect of coenzyme Q10 on the exercise performance of cross-country skiers

Ylikoski T.; Piirainen J.; Hanninen O.; Penttinen J.
Molecular Aspects of Medicine (United Kingdom), 1997, 18/SUPPL. (S283-S290)

Coenzyme Q10, supplementation (Bio-Qinon Pharma Nord, 90 mg/day) was studied in a double-blind cross-over study of 25 Finnish top-level cross-country skiers. With CoQ10 supplementation, all measured indexes of physical performance (AET, ANT and VO2Max) improved significantly.

During verum supplementation, 94% of the athletes felt that the preparation had been beneficial in improving their performance and recovery time vs. only 33% in the placebo periods.



T-2 toxin-induced DNA damage in mouse livers: The effect of pretreatment with coenzyme Q10 and alpha-tocopherol

Atroshi F.; Rizzo A.; Biese I.; Veijalainen P.; Antila E.; Westermarck T.,
Molecular Aspects of Medicine (United Kingdom), 1997, 18/SUPPL. (S255-S258)

Active oxygen species are reported to cause organ damage. This study was therefore designed to determine whether oxidative stress contributed to the initiation or progression of hepatic DNA damage produced by T-2 toxin. The aim of the study was also to investigate the behavior of the antioxidants coenzyme Q10 (CoQ10), and alpha-tocopherol (vitamin E) against DNA damage in the livers of mice fed T-2 toxin. Treatment of fasted mice with a single dose of T-2 toxin (1.8 or 2.8 mg/kg body weight) by oral gavage led to 76% hepatic DNA fragmentation. T-2 toxin also decreased hepatic glutathione (GSH) levels markedly. Pretreatment with CoQ10 (6 mg/kg) together with alpha-tocopherol (6 mg/kg) decreased DNA damage. The CoQ10 and vitamin E showed some protection against toxic cell death and glutathione depletion caused by T-2 toxin. Oxidative damage caused by T-2 toxin may be one of the underlying mechanisms for T-2 toxin-induced cell injury and DNA damage, which eventually lead to tumorigenesis.



The mechanisms of coenzyme Q10 as therapy for myocardial ischemia reperfusion injury

Whitman G.J.R.; Niibori K.; Yokoyama H.; Crestanello J.A.; Lingle D.M.; Momeni R. G.J.R. Whitman.
Molecular Aspects of Medicine (United Kingdom), 1997, 18/SUPPL. (S195-S203)

It has been hypothesized that CoQ10 pretreatment protects myocardium from ischemia reperfusion (I/R) injury by its ability to increase aerobic energy production as well as its activity as an antioxidant. Isolated hearts from rats pretreated with either CoQ10 20 mg/kg i.m. and 10 mg/kg i.p. or vehicle 24 hours and 2 hours prior to the experiment, were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and 40 min of reperfusion (RP).

Developed pressure, plus or minus dp/dt, myocardial oxygen consumption, and myocardial aerobic efficiency (DP/MVO2) were measured. 31P NMR spectroscopy was used to determine ATP and PCr concentrations. Lucigenin-enhanced chemiluminescence of the coronary sinus effluent was utilized to determine oxidative stress through the protocol.

CoQ10 pretreatment improved myocardial function after ischemia reperfusion. CoQ10 pretreatment improved tolerance to myocardial ischemia reperfusion injury by its ability to increase aerobic energy production, and by preserving myocardial aerobic efficiency during reperfusion. Furthermore, the oxidative burst during RP was diminished with CoQ10. Similarly it was hypothesized that CoQ10 protected coronary vascular reactivity after I/R via an antioxidant mechanism. Utilizing a newly developed liposomal CoQ10 preparation given i.v. 15 min prior to ischemia, ischemia reperfusion was carried out on Langendorff apparatus as previously described. Just prior to ischemia and after RP, hearts were challenged with bradykinin (BK) and sodium nitroprusside (SNP) and change in coronary flow was measured. CoQ10 pretreatment protected endothelial-dependent and endothelial-independent vasodilation after I/R.

We conclude that CoQ10 pretreatment protects coronary vascular reactivity after I/R via OH radical scavenger action.



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

Langsjoen H; Langsjoen P; Langsjoen P; Willis R; Folkers K
University of Texas Medical Branch, Galveston 77551, USA.
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, overall medication 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.



Perspectives on therapy of cardiovascular diseases with coenzyme Q10 (ubiquinone)

Mortensen SA
Department of Cardiology and Internal Medicine, Rigshospitalet B 2142, State University Hospital, Copenhagen
Clin Investig (GERMANY) 1993, 71 (8 Suppl) pS116-23,

A defective myocardial energy supply-due to lack of substrates and/or essential cofactors and a poor utilization efficiency of oxygen-may be a common final pathway in the progression of myocardial diseases of various etiologies. The vitamin-like essential substance coenzyme Q10, or ubiquinone, is a natural antioxidant and has a key role in oxidative phosphorylation. A biochemical rationale for using coenzyme Q10 as a therapy in heart disease was established years ago by Folkers and associates; however, this has been further strengthened by investigations of viable myocardial tissue from the author's series of 45 patients with various cardiomyopathies. Myocardial tissue levels of coenzyme Q10 determined by high-performance lipid chromatography were found to be significantly lower in patients with more advanced heart failure compared with those in the milder stages of heart failure. Furthermore, the myocardial tissue coenzyme Q10 deficiency might be restored significantly by oral supplementation in selected cases. In the author's open clinical protocol study with coenzyme Q10 therapy (100 mg daily) nearly two-thirds of patients revealed clinical improvement, most pronounced in those with dilated cardiomyopathy. Double-blind placebo-controlled trials have definitely confirmed that coenzyme Q10 has a place as adjunctive treatment in heart failure with beneficial effects on the clinical outcome, the patients' physical activity, and their quality of life. The positive results have been above and beyond the clinical status obtained from treatment with traditional principles-including angiotensin-converting enzyme inhibitors.



Coenzyme Q10: a new drug for cardiovascular disease

Greenberg S; Frishman WH
Department of Medicine, Mt. Sinai Hospital and Medical Center, New York, New York
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 myocardial ischemia 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.



Treatment of essential hypertension with coenzyme Q10

Langsjoen P; Langsjoen P; Willis R; Folkers K
Institute for Biomedical Research, University of Texas, Austin 78712, USA.
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.



Coenzyme Q10 in essential hypertension

Digiesi V; Cantini F; Oradei A; Bisi G; Guarino GC; Brocchi A; Bellandi F; Mancini M; Littarru GP
Third institute of Clinical Medicine and Medical Therapy, University of Florence Medical School, Italy
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.



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 change or 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 improved quality 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 have established 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 ratios 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, overall medication 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 a 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 myocardial ischemia 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 in blood 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.



Prospects for nutritional control of hypertension

Med Hypotheses (ENGLAND) Mar 1981, 7 (3) p271-83

Sodium restriction is not the only nutritional measure likely to prove valuable in the treatment and prevention of hypertension. The hypotensive effects of central adrenergic stimulation can be promoted by supplementary tyrosine, insulin potentiation (as with GTF), and (possibly) high-dose pyridoxine. Insulin potentiators (GTF) and prostaglandin precursors (essential fatty acids) should have direct relaxant effects on vascular muscle. A high potassium, low sodium diet, coenzyme Q, and prevention of cadmium toxicity (as with dietary selenium) may act to offset renally-mediated pressor influences. Functional combinations of these measures might prove to be substantially effective, in which case they would offer considerable advantages over potentially toxic drug therapies.



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.



Fish oil and other nutritional adjuvants for treatment of congestive heart failure

Medical Hypotheses (United Kingdom), 1996, 46/4 (400-406)

Published clinical research, as well as various theoretical considerations, suggest that supplemental intakes of the 'metavitamins' taurine, coenzyme Q10, and L-carnitine, as well as of the minerals magnesium, potassium, and chromium, may be of therapeutic benefit in congestive heart failure. High intakes of fish oil may likewise be beneficial in this syndrome. Fish oil may decrease cardiac afterload by an antivasopressor action and by reducing blood viscosity, may reduce arrhythmic risk despite supporting the heart's beta-adrenergic responsiveness, may decrease fibrotic cardiac remodeling by impeding the action of angiotensin II and, in patients with coronary disease, may reduce the risk of atherothrombotic ischemic complications. Since the measures recommended here are nutritional and carry little if any toxic risk, there is no reason why their joint application should not be studied as a comprehensive nutritional therapy for congestive heart failure.



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.

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