Medically reviewed by Drugs.com. Last updated on Dec 20, 2018.
Scientific Name(s): Coenzyme Q-10, Mitoquinone, Ubidecarenone
Common Name(s): Adelir, Coenzyme Q10, Heartcin, Inokiton, Neuquinone, Taidecanone, Ubiquinone, Udekinon
Ubiquinone may have applications in cardiovascular disease, especially congestive heart failure (CHF), although there is a lack of consensus. Studies in neurological disorders are less promising. Limited clinical trials have been conducted to support widespread use for other conditions.
Cardiovascular and neurologic trials predominantly use ubiquinone dosages of 300 mg/day or idebenone dosages of 5 mg/kg/day. Higher dosages of ubiquinone (up to 3,000 mg/day) have been used. Pharmacokinetic studies suggest split dosing is superior to single daily dosing.
Absolute contraindications have not been identified.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Findings are conflicting.
Adverse effects are rare and include diarrhea, GI discomfort, headache, loss of appetite, and nausea. Allergic reactions have been reported.
An observed intake safety level of 1,200 mg/day is based on clinical data; however, dosages exceeding this amount have been used with no apparent adverse effect. No accumulation in plasma or tissue following cessation of coenzyme Q10 consumption has been noted.
Ubiquinones are a class of lipid-soluble benzoquinones that are involved in mitochondrial electron transport. They are found in the majority of aerobic organisms, from bacteria to mammals, hence the name ubiquinone ("ubiquitous quinone").
The first ubiquinone was isolated in 1957. Since that time, ubiquinones have been studied extensively in Japan, Russia, and Europe, with research in the United States beginning more recently. Popular press accounts claim that roughly 12 million Japanese people use ubiquinones as the medication of choice for management of cardiovascular diseases, supplied via more than 250 commercially available preparations. Ubiquinone is touted as an effective treatment for CHF, cardiac arrhythmias, hypertension, and in reducing hypoxic injury to the myocardium. Other claims include increases in exercise tolerance, stimulation of the immune system, and counteraction of the aging process. Ubiquinone has not been approved for therapeutic use in the United States; however, it is available as a food supplement.1
Ubiquinones participate in oxidation-reduction reactions in the mitochondrial respiratory chain. They also have properties of hydrogen carriers, providing a coupling of proton translocation to respiration by means of a chemiosmotic mechanism. Ubiquinol (the reduced form of ubiquinone), present in all cellular membranes, is a recognized antioxidant that can reduce oxidized tocopherol and ascorbate after free radicals have been removed. Other membrane-related functions have been identified for coenzyme Q10, including the activation of the sodium/hydrogen ion antiporter, apoptosis control, and nicotinamide adenine dinucleotide/nicotinamide/adenine dinucleotide hydrogen ratio control. Reviews of the actions of coenzymes have been published.1, 2
Laboratory monitoring of coenzyme Q10 is possible using high-performance liquid chromatography with ultraviolet, coulometric assay or electrochemical detection.3
Uses and Pharmacology
The American College of Cardiology does not support the use of coenzyme Q10 in cardiovascular disease because a mortality benefit has not been established4 while the Agency for Healthcare Research and Quality finds no convincing evidence to either support or refute coenzyme Q10's place in therapy.5 Likewise, the clinical practice guideline from the American College of Physicians/American College of Cardiology Foundation/American Heart Association/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons regarding management of stable ischemic heart disease (2012) recommend that treatment with garlic, coenzyme Q10, selenium, or chromium should not be used with the intent of reducing cardiovascular risk or improving outcomes in patients with stable ischemic heart disease (strong recommendation; low-quality evidence).58
The widespread use of coenzyme Q10 as a supplement and the availability of numerous trial data suggesting the relative nontoxicity of the compound makes data derived from animal experiments less important.
Cardiac risk in renal disease
Patients with end-stage renal disease have a high prevalence of oxidative stress that increases their cardiovascular risk. Ubiquinone was administered for 4 months at 2 doses in a double-blind, randomized, placebo-controlled trial (n=65) to patients undergoing maintenance hemodialysis 3 times weekly to assess the effects on biomarkers of oxidative stress and cardiac function. A significantly higher mean redox ratio (reduced to oxidized CoQ10) was observed in the CoQ10 1,200 mg/day (P<0.001) but not the 600 mg/day group after adjusting for baseline values. Similarly, the mean plasma concentration of the oxidative stress biomarker F2-isoprstanes was significantly improved in the higher dose group (P=0.002) compared to placebo, which held true at 2 (P=0.005) and 4 months (P<0.001) after adjusting for baseline values. Cardiac function markers were not significantly different in either intervention group in the intent-to-treat analysis, however patients in the 1,200 mg/day CoQ10 group had significantly improved isofurans, troponin T, and N-terminal pro-brain natriuretic peptide in the per-protocol analyses (n=58; P<0.05). Treatment was generally well tolerated with overall adverse event rates of 1.3 and 0.45 for the 600-mg and 1,200-mg groups, respectively, and 0.25 for placebo. Gastrointestinal discomfort and difficulty chewing the wafer doseform were reported by 3 patients in the CoQ10 groups.63
Cardiac surgery/Cardiac arrest
The use of coenzyme Q10 in improving mitochondrial function has been evaluated in cardiac surgery. A review was published of 8 studies, in which improvements in contractility of the myocardial tissue were demonstrated in association with increases in serum coenzyme Q10.6, 7 Doses of coenzyme Q10 300 mg daily for 2 weeks prior to surgery were evaluated versus placebo.6 A randomized, placebo-controlled trial evaluated coenzyme Q10 450 mg in divided doses in conjunction with hypothermia after cardiac arrest. Increased survival was shown for the coenzyme Q10 group.8
Congestive heart failure
Several meta-analyses and systematic reviews of clinical trials in CHF have been published, with results generally being more consistent for CHF than with other disease states.4, 7, 9, 10, 11, 12, 13, 14, 66 The inclusion of 2 trials in which coenzyme Q10 failed to show an effect greater than placebo in these analyses, results in only a trend in favor of ubiquinone in improving cardiac function (an increase in resting ejection fraction of 1.9% [95% confidence interval [CI], −0.13% to 3.9%]).4, 7, 9, 12 In a meta-analysis that included trials with a crossover or parallel-arm design, a 3.7% absolute difference in resting ejection fraction was found for coenzyme Q10 (95% CI, 1.59 to 5.77).7, 11 The studies, however, either do not evaluate or are underpowered to evaluate mortality outcomes.7, 11, 15 Because differing ubiquinone preparations were used in the studies, both the bioavailability of the compound7, 16 and the adequacy of dosing to reach sufficient plasma coenzyme Q10 levels for effect have been questioned.13, 14 A systematic review that included 7 randomized trials and 914 patients who had received coenzyme Q10 or placebo demonstrated no significant effect on left ventricular ejection fraction or exercise capacity.66
In the Q-SYMBIO trial, 420 patients with chronic NYHA functional class III or IV heart failure were randomized to receive either coenzyme Q10 (100 mg 3 times daily) or placebo, in addition to standard therapy. Patients in coenzyme Q10 group had lower rates of cardiovascular mortality (9% vs 16%), all-cause mortality (10% vs18%), and incidence of hospitalization for heart failure at 2 years. NYHA class was improved in the coenzyme Q10 group.67
Coenzyme Q10 is not recommended as a therapy for heart failure in the 2013 American College of Cardiology/American Heart Association guidelines.68
The effect of a combination of red yeast rice plus ubiquinone on endothelial function and arterial stiffness was investigated in a double-blind, randomized, placebo-controlled trial in pharmacologically untreated hypercholesterolemic adults (n=40). Total and low-density lipoprotein-cholesterol levels improved significantly, starting after 2 months of administration, in patients randomized to treatment (10 mg monacolins from Monascus purpureus and 30 mg emulsioned coenzyme Q10) compared to placebo (P<0.05). Significant improvements were also seen in the vascular parameters; endothelial reactivity improved +6% with treatment and changed −0.3% with placebo (P<0.05). Additionally, a significant benefit was observed in arterial stiffness measurements with red yeast rice-coenzyme Q10 (P<0.05). No significant changes were documented between groups in triglycerides, high-density lipoprotein-cholesterol, glucose, transaminases, creatine, or creatine phosphokinase.62
Systematic reviews and meta-analyses have been conducted evaluating coenzyme Q10 in hypertension versus placebo. Trials comparing coenzyme Q10 with conventional therapy are lacking.7, 12, 17 Decreases in systolic pressure were found in some patients. However, confounding variables, small trial size, and variable study designs make extrapolation of the data difficult.7, 12
Friedreich ataxia (hypertrophic cardiomyopathy)
Most studies used an open-label design.7, 18 Idebenone, an analog of coenzyme Q10, was commonly employed in these trials at dosages of 5 mg/kg/day to a maximum of 300 mg/day19 and used for periods of 6 months to 5 years.19, 20, 21, 22, 23 Increases in heart and skeletal muscle bioenergetics are reported for all the studies, as well as decreases in ventricular hypertrophy (left ventricular mass index).19, 20, 21, 22, 23 Results for fractional shortening and ejection fraction are mixed, with 1 study reporting a deterioration23 and another citing improvement in cardiac function.22
Reversal of statin-induced myopathy
Statins (HMG-CoA reductase inhibitors) deplete circulating coenzyme Q10 levels by interfering with its biosynthesis.7, 10, 24 Most studies indicate a correlation between the decrease in serum coenzyme Q10 and decreases of total and low-density lipoprotein cholesterol levels. This effect may be particularly important in elderly patients, in whom coenzyme Q10 levels are already compromised, and is also associated with higher dosages (lower dosages do not seem to affect intramuscular levels of coenzyme Q10).24, 25 The use of ezetimibe alone or in combination with a statin does not offer protection against depletion of coenzyme Q10.10, 24 No correlation has been established for decreased serum coenzyme Q10 and cardiovascular events.7, 24 Supplemental coenzyme Q10 increased circulating levels of the compound. However, results from randomized clinical trials are inconsistent in showing an effect on statin-associated myopathy.3, 16, 24, 26 Results of a meta-analysis of high-quality randomized, controlled trials (6 studies, N=226) found no benefit of supplemental coenzyme Q10 on plasma creatine kinase levels and equivocal results for muscle pain. Dosages ranged from 100 to 400 mg/day given for 30 to 90 days.69
Deficiencies of coenzyme Q10
Deficiencies of coenzyme Q10 have been described, predominantly affecting children, in a spectrum of diseases including infantile-onset, multisystem diseases, as well as adult-onset cerebellar ataxia and pure myopathies.28, 29 Lymphocyte and platelet coenzyme Q10 levels were lower in Down syndrome41 while lower serum levels are associated with phenylketonuria and mevalonic aciduria.42
A systematic review and meta-analysis of 7 randomized controlled trials conducted in diabetic patients (n = 356) treated with ubiquinone (coenzyme Q10) for at least 12 weeks found that neither coenzyme Q10 alone or in combination with fenofibrate improved glycemic control, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, or blood pressure. However, triglycerides were significantly improved with coenzyme Q10 monotherapy (mean difference, −0.26 mmol/L; P = 0.02). When combined with fenofibrate, triglycerides (−0.72 mmol/L; P = 0.0004) and cholesterol were significantly reduced (mean difference, −0.45 mmol/L, P = 0.02). Treatment ranged from 100 to 200 mg for 3 to 6 months.61
A 2014 Cochrane systematic review and meta-analysis on antioxidants for use in male subfertility identified 3 trials (N=479) that investigated coenzyme Q10; however, extremely high heterogeneity prevented pooling of the results. The authors suggested that compared to placebo, an effect was evident at 6 months for coenzyme Q10 on sperm motility and concentration, but data were unsuitable to draw a clear conclusion.64
Coenzyme Q10 has been evaluated in migraine versus placebo in small trials. Decreases in attack frequency, days with headache, and days with nausea were found for a daily dose of 300 mg.38 The coadministration of ubiquinone with tamoxifen mitigated the hyperlipidemia associated with tamoxifen, and tumor marker levels indicated an antiangiogenesis effect.39 An Agency for Healthcare Research and Quality review of clinical trials reported no evidence to support the use of ubiquinone in the prevention or treatment of cancer.40
The Canadian Headache Society guidelines for migraine prophylaxis (2012) strongly recommends coenzyme Q10 (100 mg 3 times daily) to eligible patients for migraine prophylaxis based on one low quality controlled trial, as does the European Federation of Neurological Societies guidelines (2009) on the treatment of migraines, considering coenzyme Q10 (300 mg daily) as third line therapy (probable efficacy) for migraine prophylaxis based on one placebo-controlled trial. 55, 56 The Scottish Intercollegiate Guidelines on headache (2008) also discusses the use of coenzyme Q10 as superior to placebo in a single small study. No recommendation regarding use is provided.57
The case for coenzyme Q10 as a treatment option in neurological (mitochondrial-related) disease is not as strong.27 The role of coenzyme Q10 in Parkinson, Alzheimer, and Huntington diseases; amyotrophic lateral sclerosis; and Friedreich ataxia is postulated but not established.2, 28, 29 The European Federation of Neurological Sciences guidelines on the clinical management of amyotrophic lateral sclerosis (2012) mention that evidence from controlled trials with coenzyme Q10 demonstrated no therapeutic benefit. No recommendation regarding its use is provided.52
Studies in Friedreich and non-Friedreich ataxia have largely shown a continued worsening of disease, as measured by the International Cooperative Ataxia Group rating scale, irrespective of idebenone use (5 mg/kg/day).19, 20, 23, 30, 31
A link between mitochondrial dysfunction and Parkinson disease has been established, but the relationship with coenzyme Q10 has not.32 A multicenter clinical trial found a decrease in worsening of symptoms in patients with early Parkinson disease receiving coenzyme Q10 1,200 mg/day, but not at lower dosages.33 Effects were not apparent at 1 month, but were evident at 8 months. Changes in daily living factors were more pronounced than clinical disease progression changes.32, 34 Increases in plasma coenzyme Q10 were recorded.33 A larger trial using higher dosages (coenzyme Q10 600 mg chewable wafers 4 times a day) found a mean change in total rating score high enough to warrant a phase 3 trial35; however, the trial was not designed to evaluate efficacy.34, 35 A phase 3, multicenter, double-blind randomized clinical trial (n = 600) found no evidence of benefit of coenzyme Q10 1,200 or 2,400 mg/day versus placebo in adults with early Parkinson disease not yet requiring dopaminergic therapy.60 The study was terminated early due to futility analysis; mean follow-up time was 10.4 months. Treatment was well tolerated.60 A multicenter trial of patients receiving anti-Parkinson medication found no difference in symptoms over placebo.36
The role of mitochondrial stress in Alzheimer disease led to more studies of coenzyme Q10.31 Multicenter clinical trials using idebenone dosages of up to 360 mg 3 times a day found no effect on the rate of decline over placebo. Analyses using various rating scales showed some differences that were not considered clinically important, mirroring other older trials.37 Similarly, no slowing of decline was noted in Huntington disease.3 The American Academy of Neurology evidence-based guidelines regarding the treatment of chorea in Huntington disease (2012) conclude that coenzyme Q10 (300 mg twice daily) is likely ineffective in moderately improving Huntington disease chorea based on a well-controlled, randomized trial. Modest benefit can not be excluded.53
Ubiquinone 400 mg once daily was evaluated for treatment of diabetic polyneuropathy in a small randomized, double-blind, 12-week study in adults with type 2 diabetes mellitus and hemoglobin A1c levels less than 12. Ubiquinone was significantly better than placebo for outcomes including neuropathy symptom and impairment scores, nerve conduction velocities, and lipid peroxidation.59
In infants with Prader-Willi syndrome, coenzyme Q10 had no effect on lean mass versus growth hormone.43
Several dosage forms exist, including compressed and chewable tablets, powder-filled and gel-filled capsules, liquid syrups, wafers, and newer solubilized formulations. The reduced form of coenzyme Q10, ubiquinol, is also commercially available.44
Pharmacokinetic studies suggest split dosing is superior to single daily dosing; for tissue uptake and crossing the blood-brain barrier, plasma coenzyme Q10 levels need to be higher than normal.44
Cardiovascular and neurologic trials predominately use ubiquinone dosages of 300 mg/day4, 7, 9, 10, 11, 12, 13, 14 or idebenone dosages of 5 mg/kg/day.19, 20, 21, 22, 23 A dose of 1,200 mg/day (but not 600 mg/day) showed promise in patients with end-stage renal disease at high cardiac risk.63 A diabetic neuropathy study used a daily dose of 400 mg.59
High-dose ubiquinone (1,200 mg/day) was used in patients with early Parkinson disease33 while dosages of 2,700 to 3,000 mg/day were used in amyotrophic lateral sclerosis trials.45, 46 An open-label study that included children evaluated tolerability of high-dose idebenone. Daily dosages of 60 mg/kg given in 3 divided doses were used for 1 month.47
Pregnancy / Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Vitamin K Antagonists: Coenzyme Q-10 may diminish the anticoagulant effect of Vitamin K Antagonists. Coenzyme Q-10 may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy.48, 65
One serious adverse event, severe gastrointestinal bleeding associated with angiodysplasia, has been considered to be possibly associated with the use of ubiquinone.60 Allergic reactions, including tongue swelling, were reported in a clinical trial.35 One open-label clinical trial involving severely affected patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome reported 2 deaths.49 On autopsy, fibrotic changes in the myocardium were observed, but a causal relationship with coenzyme Q10 was not established.50
Clinical trials evaluating high-dose idebenone found only mild GI effects, headache, and fatigue.47 Similarly, clinical trials reported mild GI effects (dyspepsia, loose stools, nausea, vomiting) for ubiquinone.45, 46, 47, 50 Urine discoloration has also been noted, with no abnormalities in urine laboratory indices.47
Potential adverse effects include abdominal discomfort, headache, nausea, and vomiting. Use with caution in patients with hepatic dysfunction.51
A review of animal experiments and clinical trials has estimated an acceptable daily intake for coenzyme Q10 to be 12 mg/kg (ie, 720 mg/day for a 60 kg person) based on a no-observed-adverse-effect level in rats of 1,200 mg/kg/day. An observed safety level based on clinical data is given as 1,200 mg/day. No accumulation in plasma or tissue following cessation of coenzyme Q10 consumption was noted and endogenous biosynthesis was not affected.51
- Ubiquitous quinone
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