續上篇
4.5.G Hypercholesterolemia; Adjunct
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Limited data available
Concomitant use with HMG-CoA reductase inhibitors resulted in increased concentrations of coenzyme Q10 with no reduction in hypocholesterolemic effect
Concomitant use with HMG-CoA reductase inhibitors resulted in increased concentrations of coenzyme Q10 with no reduction in hypocholesterolemic effect
3) Adult:
a) DIETARY SUPPLEMENTATION with coenzyme Q10 for adjunctive use with hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors resulted in increased plasma and platelet concentrations of coenzyme Q10 without reducing the efficacy of the cholesterol-lowering agent (Bargossi et al, 1994; Bargossi et al, 1994a). Patients were treated with daily doses of simvastatin 20 milligrams (mg) or simvastatin 20 mg and coenzyme Q10 100 mg for 3- and 6-month study periods. In patients treated with simvastatin alone, there was a marked decrease in total cholesterol and low density lipoprotein cholesterol as well as coenzyme Q10. In patients treated with coenzyme Q10 and simvastatin, the hypocholesterolemic effect was similar to that observed in the other group, but coenzyme Q10 concentrations in plasma and platelet were significantly increased.
4.5.H Hypertension
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Limited data indicate possible efficacy
3) Adult:
a) A deficiency of coenzyme Q10 has been demonstrated in hypertensive patients in some studies (Yamagami et al, 1975), and it has been suggested that the drug may effectively reduce blood pressure due to improved bioenergetics via correction of a deficiency state (Yamagami et al, 1976; Greenberg & Frishman, 1990b).
b) Significant decreases in systolic and diastolic blood pressure have been observed with coenzyme Q10 therapy (30 to 90 milligrams daily) in patients with essential or renovascular hypertension in uncontrolled studies, but these responses have not been consistent (Greenberg & Frishman, 1990b; Folkers et al, 1981; Yamagami et al, 1976; Yamagami et al, 1975). One small 12-week double-blind study (n=20) reported significant reductions in diastolic and systolic pressure with coenzyme Q10 (33.3 milligrams three times daily) but not placebo in hypertensive patients with low serum levels of the coenzyme and low succinate dehydrogenase coenzyme Q10 reductase activity (Greenberg & Frishman, 1990b).
c) A large multicenter, randomized trial will be needed to further assess the efficacy of coenzyme Q10 in hypertension.
b) Significant decreases in systolic and diastolic blood pressure have been observed with coenzyme Q10 therapy (30 to 90 milligrams daily) in patients with essential or renovascular hypertension in uncontrolled studies, but these responses have not been consistent (Greenberg & Frishman, 1990b; Folkers et al, 1981; Yamagami et al, 1976; Yamagami et al, 1975). One small 12-week double-blind study (n=20) reported significant reductions in diastolic and systolic pressure with coenzyme Q10 (33.3 milligrams three times daily) but not placebo in hypertensive patients with low serum levels of the coenzyme and low succinate dehydrogenase coenzyme Q10 reductase activity (Greenberg & Frishman, 1990b).
c) A large multicenter, randomized trial will be needed to further assess the efficacy of coenzyme Q10 in hypertension.
4.5.I Juvenile myopathy, encephalopathy, lactic acidosis AND stroke
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Possible minimal clinical benefit
Limited data available, disorder rare
Limited data available, disorder rare
3) Adult:
a) In an evaluation of supplementation with coenzyme Q10 in 2 patients with a syndrome consisting of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) using tissue oximetry to measure the degree of impairment, oral doses of 200 milligrams/day resulted in improvement in one of the patients. The syndrome was classified as severe in 1 of the patients and mild in the other; the patient having the severe form demonstrated a shift to the mild pattern after 2 weeks of treatment, but disease severity the patient with the mild form was unchanged. Disease severity was assessed with a tissue oximetry pattern obtained during exercise on a bicycle ergometer and by using a measurement called the "L+P area" during exercise, defined as the area under the curve formed by the combined serum lactate and pyruvate concentrations on the vertical axis and time on the horizontal axis (Abe et al, 1999).
b) Despite evidence of efficacy in case reports of patients with MITOCHONDRIAL ENCEPHALOMYOPATHY (Nishikawa et al, 1989a; Ogasahara et al, 1986a), studies involving patients with a variety of mitochondrial diseases have not reported significant benefits of treatment with doses of up 300 milligrams (mg) daily for up to nine months (Matthews et al, 1993b; Scarlato et al, 1991). In one study, a response was seen in 16 of 44 patients with mitochondrial myopathy (25% reduction in exercise-induced lactate concentrations) during 6 months of therapy with coenzyme Q10 2 mg/kilogram/day; however, this change was not reproduced in responding patients during the 3-month double-blind, placebo-controlled phase of the trial that followed (Scarlato et al, 1991). Improvements seen in the open phase of this trial may have been due to variability in the natural course of the disease. One study essentially demonstrated no clinical benefit or improvement of oxidative metabolism with coenzyme Q10 given in combination with vitamins in patients (n=16) with Kearns-Sayre syndrome, myoclonic epilepsy and ragged-red fiber syndrome, mitochondrial myopathy, or combined myopathy and demyelinating neuropathy (Matthews et al, 1993b).
c) A decrease in mitochondrial ATP-generating capacity, with subsequent bioenergetic failure and tissue cell death, may be responsible for the syndromes of mitochondrial disease, including MITOCHONDRIAL MYOPATHY and encephalomyopathy (eg, KEARNS-SAYRE SYNDROME) (Matthews et al, 1993b). Due to the endogenous actions of coenzyme Q10, and reports of a relative deficiency of the coenzyme in some patients with mitochondrial disease (Ogasahara et al, 1986a), it has been suggested as rational treatment.
b) Despite evidence of efficacy in case reports of patients with MITOCHONDRIAL ENCEPHALOMYOPATHY (Nishikawa et al, 1989a; Ogasahara et al, 1986a), studies involving patients with a variety of mitochondrial diseases have not reported significant benefits of treatment with doses of up 300 milligrams (mg) daily for up to nine months (Matthews et al, 1993b; Scarlato et al, 1991). In one study, a response was seen in 16 of 44 patients with mitochondrial myopathy (25% reduction in exercise-induced lactate concentrations) during 6 months of therapy with coenzyme Q10 2 mg/kilogram/day; however, this change was not reproduced in responding patients during the 3-month double-blind, placebo-controlled phase of the trial that followed (Scarlato et al, 1991). Improvements seen in the open phase of this trial may have been due to variability in the natural course of the disease. One study essentially demonstrated no clinical benefit or improvement of oxidative metabolism with coenzyme Q10 given in combination with vitamins in patients (n=16) with Kearns-Sayre syndrome, myoclonic epilepsy and ragged-red fiber syndrome, mitochondrial myopathy, or combined myopathy and demyelinating neuropathy (Matthews et al, 1993b).
c) A decrease in mitochondrial ATP-generating capacity, with subsequent bioenergetic failure and tissue cell death, may be responsible for the syndromes of mitochondrial disease, including MITOCHONDRIAL MYOPATHY and encephalomyopathy (eg, KEARNS-SAYRE SYNDROME) (Matthews et al, 1993b). Due to the endogenous actions of coenzyme Q10, and reports of a relative deficiency of the coenzyme in some patients with mitochondrial disease (Ogasahara et al, 1986a), it has been suggested as rational treatment.
4.5.J Male infertility
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Coenzyme Q10 levels improved sperm motility but not sperm concentration or morphology in infertile men with idiopathic asthenozoospermia following 6 months of treatment with coenzyme Q10
3) Adult:
a) Coenzyme Q10 improved sperm motility but not sperm concentration or morphology in infertile men with idiopathic asthenozoospermia following 6 months of treatment with coenzyme Q10 in an open, uncontrolled trial. Twenty-two men (mean age, 31 years) received coenzyme Q10 100 milligrams twice daily orally for 6 months. Motility improved after 6 months (p less than 0.05). Neither sperm concentration nor morphology improved after 6 months. The authors concluded that coenzyme Q10's role in the treatment of asthenozoospermia may be related to its antioxidation and mitochondrial respiratory chain roles (Balercia et al, 2004a).
4.5.K Migraine; Prophylaxis
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Reduced headache frequency in patients with episodic migraine
Did not affect headache severity
Did not affect headache severity
3) Adult:
a) Daily use of supplemental coenzyme Q10 reduced migraine frequency in 29 of 31 patients with episodic migraine (with or without aura) in an open-label study. Subjects took oral coenzyme Q10 150 milligrams (mg) daily with breakfast for 3 months after a 1-month baseline period. Sixty-one percent of the patients had a 50% or greater reduction in number of days with migraine headache. Two patients showed no improvement in migraine frequency. Average headache frequency was reduced from 7.34 days during the 30-day baseline to 2.95 days during the last 60 days of treatment (p less than 0.002). Headache intensity was not affected. No side effects were observed (Rozen et al, 2002).
4.5.L Operation on heart
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Variable efficacy in preventing a low output state and preserving ischemic myocardium in patients undergoing heart surgery
All studies involve small subject groups
All studies involve small subject groups
3) Adult:
a) A placebo-controlled study reported less dramatic benefits of coenzyme Q10 in patients undergoing bypass surgery than reported previously. Oral coenzyme Q10 150 to 200 milligrams daily was given for 5 to 7 days presurgery, and except for a wider pulse pressure with coenzyme Q10, postoperative hemodynamics did not differ significantly between groups; however, a trend toward a lower frequency of low cardiac output and lower left atrial pressure was seen in the coenzyme Q10 group. Ultrastructural studies demonstrated better preservation of right and left ventricular myocardium with coenzyme Q10, although there was no significant effect of the drug on the atrial myocardium (Chen et al, 1994).
b) Administration of oral coenzyme Q10 100 milligrams daily for two weeks prior to surgery and one month postoperatively was demonstrated to produce beneficial effects on myocardial preservation in high-risk patients with low blood coenzyme Q10 levels undergoing coronary artery-vein graft or valvular plus vein graft bypass surgery in a double-blind study. Significant increases in blood and myocardial coenzyme Q10 levels as well as myocardial adenosine triphosphate (ATP) were observed after presurgical treatment, which were preserved during surgery. Compared to the placebo control group, significant increases in cardiac index and left-ventricular ejection fraction were evident postsurgery in patients treated with coenzyme Q10, corresponding to maintenance of blood and tissue coenzyme Q10 levels and ATP tissue levels. The recovery course was shorter in the coenzyme Q10 group (3 to 5 days versus 15 to 30 days); recovery complications were seen only in the placebo group (Judy et al, 1993a).
c) Other open studies have shown benefits of oral coenzyme Q10 in protecting against low cardiac output in the postoperative period after bypass grafting or valve replacement surgery. Less creatine kinase MB loss during extracorporeal circulation and a tendency toward lower requirements for inotropic support have been observed (Mortensen, 1993a; Greenberg & Frishman, 1990b).
b) Administration of oral coenzyme Q10 100 milligrams daily for two weeks prior to surgery and one month postoperatively was demonstrated to produce beneficial effects on myocardial preservation in high-risk patients with low blood coenzyme Q10 levels undergoing coronary artery-vein graft or valvular plus vein graft bypass surgery in a double-blind study. Significant increases in blood and myocardial coenzyme Q10 levels as well as myocardial adenosine triphosphate (ATP) were observed after presurgical treatment, which were preserved during surgery. Compared to the placebo control group, significant increases in cardiac index and left-ventricular ejection fraction were evident postsurgery in patients treated with coenzyme Q10, corresponding to maintenance of blood and tissue coenzyme Q10 levels and ATP tissue levels. The recovery course was shorter in the coenzyme Q10 group (3 to 5 days versus 15 to 30 days); recovery complications were seen only in the placebo group (Judy et al, 1993a).
c) Other open studies have shown benefits of oral coenzyme Q10 in protecting against low cardiac output in the postoperative period after bypass grafting or valve replacement surgery. Less creatine kinase MB loss during extracorporeal circulation and a tendency toward lower requirements for inotropic support have been observed (Mortensen, 1993a; Greenberg & Frishman, 1990b).
4.5.M Parkinson's disease
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
- Coenzyme Q10 1200 milligrams/day may slow the progression of early Parkinson disease; larger studies are needed.
3) Adult:
a) Coenzyme Q10 1200 milligrams (mg)/day appeared to reduce measures of functional decline in Parkinson disease in a double-blind, placebo- controlled, randomized, multicenter, dose-ranging trial designed to detect a trend toward efficacy. Eighty patients with early Parkinson disease were divided into four treatment groups: placebo (n=16), coenzyme Q10 300 mg/day (n=21), coenzyme Q10 600 mg/day (n=20), and coenzyme Q10 1200 mg/day (n=23). All subjects received vitamin E 1200 international units daily to aid in the absorption of coenzyme Q10 and were followed for 16 months. The primary response variable was the change in the total score on the Unified Parkinson Disease Rating Scale (UPDRS) from baseline to last visit. Only coenzyme Q10 1200 mg reduced the UPDRS score compared with placebo (UPDRS 6.69 and 11.99, respectively, a difference of 5.3 points (95% CI 0.21 to 10.39), p=0.09), determined to be statistically significant to detect a trend toward efficacy by the authors. Coenzyme Q10 did not affect the time until patients required levodopa therapy. Coenzyme Q10 increased the activity of the electron transport chain as measured by mitochondrial assay (p=0.04). The authors speculate that an increase in the electron transport chain of complex I (mediated by coenzyme Q10) inside the mitochondria may be the mechanism of action. This study had a power of 73% to detect a change in the UPDRS score of 6 points (Shults et al, 2002).
4.5.N Periodontal disease
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Limited data show some efficacy in producing improvements in periodontal disease
3) Adult:
a) A gingival and leukocyte deficiency of coenzyme Q10 has been reported in patients with periodontal disease (Hansen et al, 1976; Nakamura et al, 1974; Littarru et al, 1971). Oral therapy with this agent has been effective in producing improvements in periodontal disease patients in case reports and small studies (one controlled) (Wilkinson et al, 1976a; Iwamoto et al, 1975; Wilkinson et al, 1975).
b) In a small study, coenzyme Q10 appeared to effect improvement in periodontal disease. Coenzyme Q10 25 milligrams twice daily or placebo was randomly administered to 18 patients with severe periodontal disease and measurable pockets for 3 weeks. All 8 patients receiving oral coenzyme Q10 displayed a significant improvement in periodontal disease. Seven of ten placebo-treated patients did not improve clinically. Of the remaining 3 placebo-treated patients, 2 patients improved due to better oral hygiene and 1 patient was clinically marginal and could have been assigned to either outcome group (Wilkinson et al, 1976a).
c) In a small study, patients with advanced periodontitis received coenzyme Q10 50 milligrams (mg) per day orally (7 patients) or hexahydrocoenzyme Q4 1000 mg/day (1 patient) for 21 days. The hexahydrocoenzyme Q4 was formulated as a dragee and was allowed to slowly dissolve in the mouth. Plaque control was maintained during therapy. Extraordinary healing of the diseased tissues occurred 5 to 7 days post-biopsy. An unexpected finding was a significant reduction in the periodontal pocket depth. No adverse effects were reported with either drug. The investigators concluded that coenzyme Q10 could be useful in treating periodontal disease (Wilkinson et al, 1975).
b) In a small study, coenzyme Q10 appeared to effect improvement in periodontal disease. Coenzyme Q10 25 milligrams twice daily or placebo was randomly administered to 18 patients with severe periodontal disease and measurable pockets for 3 weeks. All 8 patients receiving oral coenzyme Q10 displayed a significant improvement in periodontal disease. Seven of ten placebo-treated patients did not improve clinically. Of the remaining 3 placebo-treated patients, 2 patients improved due to better oral hygiene and 1 patient was clinically marginal and could have been assigned to either outcome group (Wilkinson et al, 1976a).
c) In a small study, patients with advanced periodontitis received coenzyme Q10 50 milligrams (mg) per day orally (7 patients) or hexahydrocoenzyme Q4 1000 mg/day (1 patient) for 21 days. The hexahydrocoenzyme Q4 was formulated as a dragee and was allowed to slowly dissolve in the mouth. Plaque control was maintained during therapy. Extraordinary healing of the diseased tissues occurred 5 to 7 days post-biopsy. An unexpected finding was a significant reduction in the periodontal pocket depth. No adverse effects were reported with either drug. The investigators concluded that coenzyme Q10 could be useful in treating periodontal disease (Wilkinson et al, 1975).
4.5.O Pulmonary fibrosis
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Possible improvement in pulmonary function, but data is limited and not reliable
3) Adult:
a) Therapy with coenzyme Q10 appears to improve pulmonary function and exercise performance in patients with chronic lung disease (Fujimoto et al, 1993). The effects of CoQ10 treatment (ie ventilatory capacity, arterial oxygen (PaO2), and exercise performance) were evaluated in 21 patients with CHRONIC OBSTRUCTIVE LUNG DISEASE (COPD) and 9 patients with IDIOPATHIC PULMONARY FIBROSIS (IPF). Patients were given 90 milligrams daily for 8 weeks. Patients with hypoxemia at rest tended to have lower CoQ10 levels, (0.56 micrograms/milliliter (mcg/mL) for COPD patients and 0.45 mcg/mL for IPF patients) and those with exercise-induced hypoxemia also had reduced levels. After 8 weeks of treatment, the blood levels of CoQ10 had risen from 0.33 mcg/mL at baseline to 0.90 mcg/mL (P less than 0.01). Ventilatory capacity had also risen from 2.54 to 2.71 liters, the PaO2 increased from 74.5 to 81.5 torr (P less than 0.05), and the treadmill time increased from 12 to 14 minutes (P less than 0.02), respectively. Under these low level conditions, some organs, including the heart, liver, and skeletal muscles, may become hypoxic. During treatment, however, there was no significant difference in oxygen consumption compared to baseline. Heart rate during exercise was significantly decreased and PaO2 was significantly improved. Another result of CoQ10 administration was improved oxygen transport to muscles during exercise, due to the improved PaO2 and increased cardiac output. This study suggests that CoQ10 has a favorable effect on the energy production of exercising muscles in patients with chronic lung diseases who have hypoxemia at rest or during exercise.
b) Coenzyme Q10 50 milligrams daily was superior to placebo in increasing maximal oxygen consumption and expired volume in patients with chronic obstructive pulmonary disease (COPD) in a double-blind study (Satta et al, 1991). However, deficiencies were apparent in this study (eg, interpretation of results with respect to statistical analysis) and its results require confirmation.
b) Coenzyme Q10 50 milligrams daily was superior to placebo in increasing maximal oxygen consumption and expired volume in patients with chronic obstructive pulmonary disease (COPD) in a double-blind study (Satta et al, 1991). However, deficiencies were apparent in this study (eg, interpretation of results with respect to statistical analysis) and its results require confirmation.
4.5.P Ventricular arrhythmia
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Limited data demonstrate shortening of QT interval
3) Adult:
a) Therapy with coenzyme Q10 has shown efficacy in treating VENTRICULAR ARRHYTHMIAS (premature ventricular contractions (PVCs)) in limited studies, producing response rates of up to 25%. A shortening of the QT interval was seen consistently in these studies (Greenberg & Frishman, 1990b). Antiarrhythmic efficacy requires further evaluation in controlled trials.
6.0 References
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