Research & Case History Support

1. Stocker R, Bowry VW, Frei B. .Ubiquinol-10 protects human low density lipoprotein more

efficiently against lipid peroxidation than does alpha-tocopherol. .Proc Natl Acad Sci

1991;88:1646-1650.

2. Langsjoen PH, Langsjoen PH, Folkers K..Long-term efficacy and safety of coenzyme

Q10 therapy for idiopathic dilated cardiomyopathy..Am J Cardiol 1990;65:521-523.

3. Littarru GP, Ho L, Folkers K. Deficiency of coenzyme Q10 in human heart disease. Part I.

Int J Vitam Nutr Res 1972;42:291-305.

4. Folkers K, Littarru GP, Ho L, Runge TM, Havanonda S, Cooley D. .Evidence for a

deficiency of coenzyme Q10 in human heart disease. .Int J Vitam Nutr Res 1970;40:380-

390.

5. Folkers K, Vadhanavikit S, Mortensen SA. .Biochemical rationale and myocardial tissue

data on the effective therapy of cardiomyopathy. with coenzyme Q10.. Proc Natl Acad Sci

1985;82:901-904.

6. Langsjoen PH, Vadhanavikit S, Folkers K., .Effective treatment with coenzyme Q10 of

patients with chronic myocardial disease.. Drugs Exptl Clin Res 1985;11:577-579.

7. Yamamura Y, Ishiyama T, Yamagami T, Morita Y, Ishio S, Kashiwamura S, et. al.

.Clinical use of coenzyme-Q for treatment of cardiovascular disease. Jpn Circ J

1967;31:168. (In this study, CoQ7 was used;

however, this compound is apparently

converted by the body into CoQ10.)

8. Ishiyama T, Morita Y, Toyama S, Yamagami T, Tsukamoto N, Wada N, et. al. A clinical study

of the effect of coenzyme Q on congestive heart failure.. Jpn Heart J 1976;17:32-42.

9. Mortensen SA, Vadhanavikit S, Baandrup U, Folkers K. .Long-term coenzyme Q10 therapy:

a major advance in the management of resistant myocardial failure.. Drugs Exptl Clin

Res 1985;11:581-593.

10. Morisco C, Trimarco B, Condorelli M. .Effect of coenzyme Q10 in patients with congestive

heart failure: a long-term multicenter randomized study.. Clin Invest 1993;71:S134-S136.

11. Kamikawa T, Kobayashi A, Yamashita T, Hayashi H, Yamazaki N. .Effects of coenzyme

Q10 on exercise tolerance in chronic stable angina pectoris. .Am J Cardiol 1985;56:247-

251.

12. Fujioka T, Sakamoto Y, Mimura G. .Clinical study of cardiac arrhythmias using a 24-hour

continuous electrocardiographic recorder (5^th report) - antiarrhythmic action of coenzyme

Q10 in diabetics.. Tohoku J Exp Med 1983;141(Suppl):453-463.

13. Ogura R, Toyama H, Shimada T, Murakami M. .The role of ubiquinone (coenzyme Q10) in

preventing adriamycin-induced mitochondrial disorders in rat heart.. J Appl Biochem

1979;1:325-335.

14. Karlsson J, Folkers K, Astrum H, Jansson E, Pernow B, et al. .Effect of adriamycin on heart

and skeletal muscle coenzyme Q (CoQ10) in man. . In Folkers K and Yamamura Y (eds.).

Biomedical and Clinical Aspects of Coenzyme Q, volume 5, Elsevier, 1986.

15. Tanaka J, Tominaga R, Yoshitoshi M, Matsui K, Komori M, Sese A, et. al. .Coenzyme Q10:

the prophylactic effect on low cardiac output following cardiac valve replacement. .Ann

Thorac Surg 1982;33:145-151.

16. Yamagami T, Iwamoto Y, Folkers K, Blomqvist CG. .Reduction by coenzyme Q10

of hypertension induced by deoxycorticosterone and saline in rats.. Int J Vitam Nutr Res

1974;44:487-496.

17. Iwamoto Y, Yamagami T, Folkers K, Blomqvist CG. .Deficiency of coenzyme Q10

in hypertensive rats and reduction of deficiency by treatment with coenzyme Q10..

Biochem Biophys Res Commun 1974;58:743-748.

18. Digiesi V, Cantini F, Oradei A, Bisi G, Guarino GC, et al. .Coenzyme Q10 in essential

hypertension. Molec Aspects Med 1994;15(Suppl):S257-S263..

19. Langsjoen P, Langsjoen P, Willis R, Folkers K. .Treatment of essential hypertension with

coenzyme Q10.. Molec Aspects Med1994;15(Suppl):S265-S272.

20. Shigeta Y, Izumi K, Abe H. .Effect of coenzyme Q7 treatment on blood sugar and ketone

bodies of diabetics.. J Vitaminol 1966;12:293-298.

21. Kishi T, Kishi H, Folkers K. .Inhibition of cardiac CoQ10-enzymes by clinically used

drugs and possible prevention.. In: Folkers K, Yamamura Y (eds.). Biomedical and Clinical

Aspects of Coenzyme Q, Vol. 1, Elsevier/ North-Holland Biomedical Press, Amsterdam,

1977, pp. 47-62.

22. Hamada M, Kazatani Y, Ochi T, Ito T, Kokubu T. .Correlation between serum CoQ10 level

and myocardial contractility in hypertensive patients.. In: Folkers K, Yamamura Y (eds.).

Biomedical and Clinical Aspects of Coenzyme Q, Vol. 4, Elsevier Science Publishers,

Amsterdam, 1984, pp. 263-270.

Am J Health Syst Pharm 2005 Aug 1;62(15):1574-81.

Vitamin K in the treatment and prevention of osteoporosis and arterial calcification.

Adams J, Pepping J

Castle Medical Center, Kailua, HI 96814, USA.

Vitamin K is essential for the activation of vitamin K-dependent proteins, which are involved not only in blood coagulation but in bone metabolism and the inhibition of arterial calcification. Arterial calcification is an active, cell-controlled process that shares many similarities with bone metabolism. Concurrent arterial calcification and osteoporosis have been called the "calcification paradox" and occur frequently in postmenopausal women. The results of two dose-response studies have indicated that the amount of vitamin K needed for optimal gamma-carboxylation of osteocalcin is significantly higher than what is provided through diet alone and that current dosage recommendations should be increased to optimize bone mineralization. Few adverse effects have been reported from oral vitamin K. CONCLUSION: Phytonadione and menaquinone may be effective for the prevention and treatment of osteoporosis and arterial calcification.

J Card Fail 2006 Aug;12(6):464-72.

The impact of coenzyme Q10 on systolic function in patients with chronic heart failure.

Sander S, et al

University of Connecticut School of Pharmacy, Storrs, Connecticut 06269, USA.

BACKGROUND: Coenzyme Q10 (CoQ10) is an endogenous cofactor in the mitochondrial energy production. CoQ10 has been touted to improve heart failure, but its effect on systolic function is controversial. Several small, randomized controlled trials evaluating CoQ10 showed variable results and were largely underpowered. We conducted a meta-analysis of these trials to evaluate the impact of CoQ10 therapy on ejection fraction and cardiac output. METHODS AND RESULTS: A systematic literature search was conducted to identify randomized, controlled trials of CoQ10 in heart failure between 1966 and June 2005. Subgroup analysis was conducted to assess clinical heterogeneity between trials. Of the 11 trials identified, 10 evaluated ejection fraction (n = 277) and 2 evaluated cardiac output (n = 42). Doses ranged from 60 to 200 mg/day with treatment periods ranging from 1 to 6 months. There was a 3.7% net improvement in ejection fraction (95% CI 1.59-5.77; P < .00001 for statistical heterogeneity). A more profound effect among patients not receiving angiotensin-converting enzyme inhibitors was observed (6.74% [95% CI 2.63-10.86]). Cardiac output increased an average of 0.28 L/minute (95% CI 0.03-0.53; P = .96 for statistical heterogeneity). CONCLUSION: CoQ10 enhances systolic function in chronic heart failure, but its effectiveness may be reduced with concomitant use of current standard therapies.

PMID: 16911914

Diabetes Res Clin Practice 2006 Apr;72(1):100-3. Epub 2005 Oct 25.

Myocardial dysfunction in mitochondrial diabetes treated with Coenzyme Q10.

Salles JE, et al

Division of Endocrinology, Department of Medicine, Federal University of SãPaulo, Rua Botucatu, 740 0434-970 SãPaulo, SP, Brazil.

Maternally-inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. Although some previous articles have reported that this mutation may be a cause of cardiomyopathy in diabetes, the degree of cardiac involvement and a specific treatment has not been established. Here, we reported a case of a patient with MIDD who developed congestive heart failure and the therapeutic usefulness of Coenzyme Q10 (CoQ10). In our patient, after the introduction of Coenzyme Q10 150 mg/day, there was a gradual improvement on left ventricular function evaluated by echocardiography. The fractional shortening (FS) and ejection fraction (EF) increased from 26 to 34% and from 49 to 64%, respectively. No side effects were noted. Three months after CoQ10 discontinuation, the parameters of systolic function evaluated by echocardiography decreased, suggesting that CoQ10 had a beneficial effect. Identification of diabetes and cardiomyopathy due to mitochondrial gene mutation may have therapeutic implications and Coenzyme Q10 is a possible adjunctive treatment in such patients.

Ann Pharmacother 2005 Sep;39(9):1522-6. Epub 2005 Jul 26.

The role of coenzyme Q10 in heart failure.

Weant KA, Smith KM

University of Kentucky Chandler Medical Center, Lexington, KY 40536-0293, USA.

OBJECTIVE: To review the clinical data demonstrating the safety and efficacy of coenzyme Q10 (CoQ10) in heart failure (HF). DATA SOURCES: Pertinent literature was identified through MEDLINE (1966-January 2005) using the search terms coenzyme Q10, heart failure, antioxidants, and oxidative stress. Only articles written in the English language and evaluating human subjects were used. DATA SYNTHESIS: HF impairs the ability of the heart to maintain its normal cardiac output. Following an initial insult, cardiac remodeling ensues, resulting in left ventricular dilation and hypertrophy. Oxidative stress is also increased, while CoQ10 levels are decreased in patients with HF. This has led to the hypothesis that CoQ10, an antioxidant, may decrease oxidative stress, impair remodeling, and improve cardiac function. CONCLUSIONS: Large, well-designed studies on this topic are lacking. The limited data from well-designed trials indicate there may be some minor benefits with CoQ10 therapy in ejection fraction and end diastolic volume. CoQ10 therapy has been shown to be relatively safe with a low incidence of adverse effects.

Pediatric Cardiology 2005 Jul-Aug;26(4):361-6.

The effect of coenzyme Q10 on idiopathic chronic dilated cardiomyopathy in children.

Soongswang J, et al

on of Cardiology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, 10700 Bangkok, Thailand. sijsw@mahidol.ac.th

The objective of this study was to assess the effect of coenzyme Q10 (CoQ10) as supplementation to conventional antifailure drugs on quality of life and cardiac function in children with chronic heart failure due to dilated cardiomyopathy (DCM). The study was an open-label prospective study performed in two of the largest pediatric centers in Thailand from August 2000 to June 2003. A total of 15 patients with idiopathic chronic DCM were included, with the median age of 4.4 years (range, 0.6-16.3). Presenting symptoms were congestive heart failure in 12 cases (80%), cardiogenic shock in 2 cases (13.3%), and cardiac arrhythmia in 1 case (6.7%). Sixty-one percent of patients were in the New York Heart Association functional class 2 (NYHA 2), 31% in NYHA 3, and 8% in NYHA 4. Cardiothoracic ratio from chest x-ray, left ventricular ejection fraction, and left ventricular end diastolic dimension in echocardiogram were 0.62 (range, 0.55-0.78), 30% (range, 20-40), and 5.2 cm (range, 3.8-6.5), respectively. CoQ10 was given at a dosage of 3.1 ? 0.6 mg/kg/day for 9 months as a supplementation to a fixed amount of conventional antifailure drugs throughout the study. At follow-up periods of 1, 3, 6, and 9 months, NYHA functional class was significantly improved, as was CT ratio and QRS duration at 3 and 9 months follow-up with CoQ10 when compared to the baseline and post-discontinuation of CoQ10 at 9 months (range, 4.8-10.8). However, when multiple comparisons were taken into consideration, there was no statistical significant improvement. In addition to the conventional antifailure drugs, CoQ10 may improve NYHA class and CT ratio and shorten ventricular depolarization in children with chronic idiopathic DCM.

PMID: 16374685

Integr Cancer Ther, 2005 Jun;4(2):110-30.

Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity.

Conklin KA

Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1778, USA. kconklin@mednet.ucla.edu

Preclinical and clinical studies suggest that anthracycline-induced cardiotoxicity can be prevented by administering coenzyme Q10 during cancer chemotherapy that includes drugs such as doxorubicin and daunorubicin. Studies further suggest that coenzyme Q10 does not interfere with the antineoplastic action of anthracyclines and might even enhance their anticancer effects. Preventing cardiotoxicity might allow for escalation of the anthracycline dose, which would further enhance the anticancer effects. Based on clinical investigation, although limited, a cumulative dose of doxorubicin of up to 900 mg/m2, and possibly higher, can be administered safely during chemotherapy as long as coenzyme Q10 is administered concurrently. The etiology of the dose-limiting cardiomyopathy that is induced by anthracyclines can be explained by irreversible damage to heart cell mitochondria, which differ from mitochondria of other cells in that they possess a unique enzyme on the inner mitochondrial membrane. This enzyme reduces anthracyclines to their semiquinones, resulting in severe oxidative stress, disruption of mitochondrial energetics, and irreversible damage to mitochondrial DNA. Damage to mitochondrial DNA blocks the regenerative capability of the organelle and ultimately leads to apoptosis or necrosis of myocytes. Coenzyme Q10, an essential component of the electron transport system and a potent intracellular antioxidant, appears to prevent damage to the mitochondria of the heart, thus preventing the development of anthracycline-induced cardiomyopathy.

PMID: 15911925

Biofactors 2005;25(1-4):137-45.

Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failure.

Beladinelli R

Department of Cardiology and Cardiac Surgery, Ancona, Italy. r.belardinelli@fastnet.it

BACKGROUND: There is evidence that plasma CoQ(10) levels decrease in patients with advanced chronic heart failure (CHF). OBJECTIVE: To investigate whether oral CoQ(10) supplementation could improve cardiocirculatory efficiency in patients with CHF. METHODS: We studied 21 patients in NYHA class II and III (18M, 3W, mean age 59 +/- 9 years) with stable CHF secondary to ischemic heart disease (ejection fraction 37 +/- 7%), using a double-blind, placebo-controlled cross-over design. Patients were assigned to oral CoQ(10) (100 mg tid) and to placebo for 4 weeks, respectively. RESULTS: CoQ(10) supplementation resulted in a threefold increase in plasma CoQ(10) level (P < 0.0001 vs placebo). Systolic wall thickening score index (SWTI) was improved both at rest and peak dobutamine stress echo after CoQ(10) supplementation (+12.1 and 15.6%, respectively, P < 0.05 vs placebo). Left ventricular ejection fraction improved significantly also at peak dobutamine (15% from study entry P < 0.0001) in relation to a decrease in LV end-systolic volume index (from 57 +/- 7 mL/m(2) to 45 mL/m(2), P < 0.001). Improvement in the contractile response was more evident among initially akinetic (+33%) and hypokinetic (+25%) segments than dyskinetic ones (+6%). Improvement in SWTI was correlated with changes in plasma CoQ(10) levels (r = -0.52, P < 0.005). Peak VO(2) was also improved after CoQ(10) as compared with placebo (+13%, <0.005). No side effects were reported with CoQ(10). CONCLUSIONS: Oral CoQ(10) improves LV contractility in CHF without any side effects. This improvement is associated with an enhanced functional capacity.

PMID: 16873938

Georgian Med News 2005 Jan;(118):20-5.

Prevention of coronary atherosclerosis by the use of combination therapy with antioxidant coenzyme Q10 and statins.

Chapidze G, et al

The goal of the present research was to assess the efficacy of combination treatment with antioxidant coenzyme Q10 and simvastatin as well as coenzyme Q10 without statin therapy in order to prevent coronary atherosclerosis. 42 outpatients were divided into 2 groups: receiving coenzyme Q10 (Hasco-Lek, Poland) 60mg daily and its combination with simvastatin (zocor, vasilip) 10mg daily for an 8-week period. The treatment with coenzyme Q10 demonstrated its potential independent role in positive modification of oxidative stress, antiatherogenic fraction of lipid profile, atherogenic ratio, platelet aggregability. Taking into consideration the obtained results the study supports the use of coenzyme Q10 in combination with statins. Suggested attractive approach may result in complete correction of dislipidemia, reverse of endothelial dysfunction, reduce degree of oxidative stress and platelet aggregability. Consequently such a combination may be beneficial in preventing of further development of atherosclerosis in native coronary arteries as well as in bypass grafts in all coronary heart disease patients with or without myocardial revascularization.

J Thorac Cardiovascul Surgery 2005 Jan;129(1):25-32.

Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue.

Rosenfeldt F, et al

Cardiac Surgical Research Unit, Department of Cardiothoracic Surgery, Alfred Hospital, Baker Heart Research Institute, Melbourne, Australia.

OBJECTIVES: Previous clinical trials suggest that coenzyme Q(10) might afford myocardial protection during cardiac surgery. We sought to measure the effect of coenzyme Q(10) therapy on coenzyme Q(10) levels in serum, atrial trabeculae, and mitochondria; to assess the effect of coenzyme Q(10) on mitochondrial function; to test the effect of coenzyme Q(10) in protecting cardiac myocardium against a standard hypoxia-reoxygentation stress in vitro; and to determine whether coenzyme Q(10) therapy improves recovery of the heart after cardiac surgery. METHODS: Patients undergoing elective cardiac surgery were randomized to receive oral coenzyme Q(10) (300 mg/d) or placebo for 2 weeks preoperatively. Pectinate trabeculae from right atrial appendages were excised, and mitochondria were isolated and studied. Trabeculae were subjected to 30 minutes of hypoxia, and contractile recovery was measured. Postoperative cardiac function and troponin I release were assessed. RESULTS: Patients receiving coenzyme Q(10) (n = 62) had increased coenzyme Q(10) levels in serum (P = .001), atrial trabeculae (P = .0001), and isolated mitochondria (P = .0002) compared with levels seen in patients receiving placebo (n = 59). Mitochondrial respiration (adenosine diphosphate/oxygen ratio) was more efficient (P = .012), and mitochondrial malondialdehyde content was lower (P = .002) with coenzyme Q(10) than with placebo. After 30 minutes of hypoxia in vitro, pectinate trabeculae isolated from patients receiving coenzyme Q(10) exhibited a greater recovery of developed force compared with those in patients receiving placebo (46.3% +/- 4.3% vs 64.0% +/- 2.9%, P = .001). There was no between-treatment difference in preoperative or postoperative hemodynamics or in release of troponin I. CONCLUSIONS: Preoperative oral coenzyme Q(10) therapy in patients undergoing cardiac surgery increases myocardial and cardiac mitochondrial coenzyme Q(10) levels, improves mitochondrial efficiency, and increases myocardial tolerance to in vitro hypoxia-reoxygenation stress.

PMID: 15632821

Clin Cardiology 2004 May;27(5):295-9.

Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study.

Berman M, et al

Department of Cardiothoracic Surgery, Heart-Lung Transplant Unit, Rabin Medical Center, Beilinson Campus, Potah Tikva, Israel. mariusby@yahoo.com

BACKGROUND: The number of patients awaiting heart transplantation is increasing in proportion to the waiting period for a donor. Studies have shown that coenzyme Q10 (CoQ10) has a beneficial effect on patients with heart failure. HYPOTHESIS: The purpose of the present double-blind, placebo-controlled, randomized study was to assess the effect of CoQ10 on patients with end-stage heart failure and to determine if CoQ10 can improve the pharmacological bridge to heart transplantation. METHODS: A prospective double-blind design was used. Thirty-two patients with end-stage heart failure awaiting heart transplantation were randomly allocated to receive either 60 mg U/day of Ultrasome--CoQ10 (special preparation to increase intestinal absorption) or placebo for 3 months. All patients continued their regular medication regimen. Assessments included anamnesis with an extended questionnaire based partially on the Minnesota Living with Heart Failure Questionnaire, 6-min walk test, blood tests for atrial natriuretic factor (ANF) and tumor necrosis factor (TNF), and echocardiography. RESULTS: Twenty-seven patients completed the study. The study group showed significant improvement in the 6-min walk test and a decrease in dyspnea, New York Heart Association (NYHA) classification, nocturia, and fatigue. No significant changes were noted after 3 months of treatment in echocardiography parameters (dimensions and contractility of cardiac chambers) or ANF and TNF blood levels. CONCLUSIONS: The administration of CoQ10 to heart transplant candidates led to a significant improvement in functional status, clinical symptoms, and quality of life. However, there were no objective changes in echo measurements or ANF and TNF blood levels. Coenzyme Q10 may serve as an optional addition to the pharmacologic armamentarium of patients with end-stage heart failure. The apparent discrepancy between significant clinical improvement and unchanged cardiac status requires further investigation.

PMID: 15188947

Mol Cell Biochem 2003 Apr;246(1-2):75-82.

Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction.

Singh RB, et al

Medical Hospital and Research Centre, Moradabad, India. icn@mickyonline.com

In a randomized, double-blind, controlled trial, the effects of oral treatment with coenzyme Q10 (CoQ10, 120 mg/day), a bioenergetic and antioxidant cytoprotective agent, were compared for 1 year, on the risk factors of atherosclerosis, in 73 (CoQ, group A) and 71 (B vitamin group B) patients after acute myocardial infarction (AMI). After 1 year, total cardiac events (24.6 vs. 45.0%, p < 0.02) including non-fatal infarction (13.7 vs. 25.3%, p < 0.05) and cardiac deaths were significantly lower in the intervention group compared to control group. The extent of cardiac disease, elevation in cardiac enzymes, left ventricular enlargement, previous coronary artery disease and elapsed time from symptom onset to infarction at entry to study showed no significant differences between the two groups. Plasma level of vitamin E (32.4 +/- 4.3 vs. 22.1 +/- 3.6 umol/L) and high density lipoprotein cholesterol (1.26 +/- 0.43 vs. 1.12 +/- 0.32 mmol/L) showed significant (p < 0.05) increase whereas thiobarbituric acid reactive substances, malondialdehyde (1.9 + 0.31 vs. 3.1 + 0.32 pmol/L) and diene conjugates showed significant reduction respectively in the CoQ group compared to control group. Approximately half of the patients in each group (n = 36 vs. 31) were receiving lovastatin (10 mg/day) and both groups had a significant reduction in total and low density lipoprotein cholesterol compared to baseline levels. It is possible that treatment with CoQ10 in patients with recent MI may be beneficial in patients with high risk of atherothrombosis, despite optimal lipid lowering therapy during a follow-up of 1 year. Adverse effect of treatments showed that fatigue (40.8 vs. 6.8%, p < 0.01) was more common in the control group than CoQ group.

PMID: 12841346

J Hum Hypertension 1999 Mar;13(3):203-8.

Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease.

Singh RB, et al

NKP Salve Institute of Medical Science, Nagpur, India.

In a randomised, double-blind trial among patients receiving antihypertensive medication, the effects of the oral treatment with coenzyme Q10 (60 mg twice daily) were compared for 8 weeks in 30 (coenzyme Q10: group A) and 29 (B vitamin complex: group B) patients known to have essential hypertension and presenting with coronary artery disease (CAD). After 8 weeks of follow-up, the following indices were reduced in the coenzyme Q10 group: systolic and diastolic blood pressure, fasting and 2-h plasma insulin, glucose, triglycerides, lipid peroxides, malondialdehyde and diene conjugates. The following indices were increased: HDL-cholesterol, vitamins A, C, E and beta-carotene (all changes P<0.05). The only changes in the group taking the B vitamin complex were increases in vitamin C and beta-carotene (P<0.05). These findings indicate that treatment with coenzyme Q10 decreases blood pressure possibly by decreasing oxidative stress and insulin response in patients with known hypertension receiving conventional antihypertensive drugs.

PMID: 10204818

Cardiovasc Drugs Ther 1998 Sep;12(4):347-53.

Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction.

Singh RB, et al

Heart Research Laboratory, Centre of Nutrition Medical Hospital and Research Centre, Moradabad, India.

The effects of oral treatment with coenzyme Q10 (120 mg/d) were compared for 28 days in 73 (intervention group A) and 71 (placebo group B) patients with acute myocardial infarction (AMI). After treatment, angina pectoris (9.5 vs. 28.1), total arrhythmias (9.5% vs. 25.3%), and poor left ventricular function (8.2% vs. 22.5%) were significantly (P < 0.05) reduced in the coenzyme Q group than placebo group. Total cardiac events, including cardiac deaths and nonfatal infarction, were also significantly reduced in the coenzyme Q10 group compared with the placebo group (15.0% vs. 30.9%, P < 0.02). The extent of cardiac disease, elevation in cardiac enzymes, and oxidative stress at entry to the study were comparable between the two groups. Lipid peroxides, diene conjugates, and malondialdehyde, which are indicators of oxidative stress, showed a greater reduction in the treatment group than in the placebo group. The antioxidants vitamin A, E, and C and beta-carotene, which were lower initially after AMI, increased more in the coenzyme Q10 group than in the placebo group. These findings suggest that coenzyme Q10 can provide rapid protective effects in patients with AMI if administered within 3 days of the onset of symptoms. More studies in a larger number of patients and long-term follow-up are needed to confirm our results.

PMID: 9825179

J Card Fail, 1995 Mar;1(2):101-7.

Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group.

Hofman-Bang C, et al

Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.

Seventy-nine patients with stable chronic congestive heart failure were randomized into a double-blind, crossover placebo controlled study with 3-month treatment periods, where either 100 mg coenzyme Q10 (CoQ10) or placebo was added to conventional therapy. Mean patient age was 61 +/- 10 years, ejection fraction at rest was 22% +/- 10%, and maximal exercise tolerance was 91 +/- 30 W. The follow-up examinations included ejection fraction (primary objective), exercise test, and quality of life questions. Ejection fraction at rest, during a slight volume load, and during a submaximal supine exercise increased slightly compared with placebo: 24% +/- 12% versus 23% +/- 12% (NS), 25% +/- 13% versus 23% +/- 12% (P < .05), and 23% +/- 11% versus 22% +/- 11% (NS). Maximal exercise capacity increased from 94 +/- 31 W during the placebo period to 100 +/- 34 W during the CoQ10 period (P < .05). Total score for the quality of life assessment increased significantly from 107 +/- 23 during the placebo period to 113 +/- 22 during the CoQ10 period (P < .05). The results indicate that oral long-term treatment with 100 mg CoQ10 in patients with congestive heart failure only slightly improves maximal exercise capacity and the quality of life and that the clinical importance of this needs to be further evaluated.

PMID: 9420639 [

Mol Aspects Med 1994;15 Suppl:s287-94.

Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators.

Baggio E, et al

Department of Internal Medicine, V. Buzzi Hospital, Reggio Emilia.

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 which 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 rales 77.8%, 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.

PMID: 7752841

Clin Investig, 1993;71(8 Suppl):S134-6.

Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study.

Morisco C., et al

Facoltài Medicina e Chiruriga, Universitàegli Studi di Napoli Federico II.

The improved cardiac function in patients with congestive heart failure treated with coenzyme Q10 supports the hypothesis that this condition is characterized by mitochondrial dysfunction and energy starvation, so that it may be ameliorated by coenzyme Q10 supplementation. However, the main clinical problems in patients with congestive heart failure are the frequent need of hospitalization and the high incidence of life-threatening arrhythmias, pulmonary edema, and other serious complications. Thus, we studied the influence of coenzyme Q10 long-term treatment on these events in patients with chronic congestive heart failure (New York Heart Association functional class III and IV) receiving conventional treatment for heart failure. They were randomly assigned to receive either placebo (n = 322, mean age 67 years, range 30-88 years) or coenzyme Q10 (n = 319, mean age 67 years, range 26-89 years) at the dosage of 2 mg/kg per day in a 1-year double-blind trial. The number of patients who required hospitalization for worsening heart failure was smaller in the coenzyme Q10 treated group (n = 73) than in the control group (n = 118, P < 0.001). Similarly, the episodes of pulmonary edema or cardiac asthma were reduced in the control group (20 versus 51 and 97 versus 198, respectively; both P < 0.001) as compared to the placebo group. Our results demonstrate that the addition of coenzyme Q10 to conventional therapy significantly reduces hospitalization for worsening of heart failure and the incidence of serious complications in patients with chronic congestive heart failure.

PMID: 8241697

Klin Wochenschr, 1988 Jul 1;66(13):583-90.

Effective and safe therapy with coenzyme Q10 for cardiomyopathy.

Langsioen Ph, et al

Department of Medicine, Scott and White Clinic, Temple, Texas.

Coenzyme Q10 (CoQ10) is indispensable in mitochondrial bioenergetics and for human life to exist. 88/115 patients completed a trial of therapy with CoQ10 for cardiomyopathy. Patients were selected on the basis of clinical criteria, X-rays, electrocardiograms, echocardiography, and coronary angiography. Responses were monitored by ejection fractions, cardiac output, and improvements in functional classifications (NYHA). Of the 88 patients 75%-85% showed statistically significant increases in two monitored cardiac parameters. Patients with the lowest ejection fractions (approx. 10%-30%) showed the highest increases (115 delta %-210 delta %) and those with higher ejection fractions (50%-80%) showed increases of approx. 10 delta %-25 delta % on therapy. By functional classification, 17/21 in class IV, 52/62 in class III, and 4/5 in class II improved to lower classes. Clinical responses appeared over variable times, and are presumably based on mechanisms of DNA-RNA-protein synthesis of apoenzymes which restore levels of CoQ10 enzymes in a deficiency state. 10/21 (48%) of patients in class IV, 26/62 (42%) in class III, and 2/5 (40%) in class II had exceptionally low control blood levels of CoQ10. Clinical responses on therapy with CoQ10 appear maximal with blood levels of approx. 2.5 micrograms CoQ10/ml and higher during therapy.

PMID: 3062263

J Mol Cell Cardiology, 1987 Jan;19(1):63-71.

The effect of treatment with coenzyme Q10 on the mitochondrial function and superoxide radical formation in cardiac muscle hypertrophied by mild aortic stenosis.

Guarnieri C, et al

A 40% reduction of the diameter of the ascending aorta maintained for 60 days induced the formation of a compensate cardiac hypertrophy in rabbits without changing the value of the azide insensitive Ca2+-ATPase activity in comparison to control hearts. The cardiac mitochondria isolated from constricted animals assayed in presence of glutamate and succinate did not show a change in the R.C.I. and ADP/O values in comparison to the controls, whilst the QO2 value enhanced or decreased respectively when determined with glutamate or succinate. The intramuscular injections of CoQ10 (12 mg/kg body weight/48 h) enhanced the mitochondrial CoQ10 concentrations both in the control and in the constricted animals and further increased the QO2 value determined in both groups of animals when glutamate was used as the substrate. The production of O2.- radicals by the level of the complexes I and III of the respiratory chain, did not change in the constricted animals, nor in the animals administered with CoQ10 in comparison to the control. CoQ10 augmented the rate of oxygen consumption by the submitochondrial particles only in the constricted animals. Moreover, the treatment with the coenzyme or the constriction of the aorta, did not modify the cardiac superoxide dismutase activity, but increased the glutathione peroxidase activity only in the banded animals. In addition, in the CoQ10 treated animals there was a reduction of NADH-diaphorase activity both in the control and constricted animals, while the malondialdehyde, generated during the thiobarbituric acid test, and the cardiac content of lipofuscin were decreased.

PMID: 3031317

Drugs Exp Clin Res. 1985;11(8):581-93.

Long-term coenzyme Q10 therapy: a major advance in the management of resistant myocardial failure.

Mortensen SA, et al

Coenzyme Q10 (CoQ10) treatment, orally administered as 100 mg daily dose, was initiated in a series of patients with advanced heart failure in an open, controlled design. They were all showing an insufficient response to classical therapy with diuretics and digitalis. Twelve patients with various causes of heart failure, classified clinically by echocardiography (ECHO), (12/12), and heart catheterization with endomyocardial biopsy, (10/12), were followed prospectively for a mean period of seven months. Serial assessments: Clinical examination (with questionnaire), ECG, chest X-ray, ECHO, systolic time intervals (STI) and blood levels of CoQ10 were performed. With a mean latency period of 30 days, eight out of 12 patients (67%) showed definite clinical improvement. Subjectively, the patients felt less tired, their general activity tolerance increased and dyspnoea at rest disappeared. There were obvious signs of decreased right-sided stasis (hepatic congestion). The heart rate fell significantly, and the heart volume (chest X-ray) decreased in the eight responders (although n.s.). A significant reduction in the left atrial size (ECHO) was registered, suggesting a reduced preload of the left ventricle, Furthermore, a significant decline in the PEP/LVET ratio (STI) was indicative of an improved myocardial performance. Preliminary CoQ10 withdrawal results showed severe clinical relapse with subsequent improvement on CoQ10 reinstatement, supporting the interpretation that treatment of these patients corrected a myocardial deficiency of CoQ10 and increased contractility. Hence CoQ10 appears to be an effective therapeutic agent in advanced cases of heart failure. This is an attractive circumvention of the traditional principles of therapy: supporting the myocardium directly by ameliorating a supposed underlying mitochondrial dysfunction (exhausted bioenergetics).

PMID: 3836876

Drugs Exp Clin Res. 1985;11(8):539-45.

Research on coenzyme Q10 in clinical medicine and in immunomodulation.

Folkers K, Wolaniuk A

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.

PMID: 3836873