Coenzyme Q10

K K Jain MD†

Neuropharmacology & Neurotherapeutics

Updated 09.04.2021
Released 12.02.2003
Expires For CME 09.04.2024

Coenzyme Q10

Author: K K Jain MD†

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Coenzyme Q10

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Introduction

Historical note and terminology

Coenzyme Q10 (ubiquinone), a vitamin, was discovered in 1957 by Frederick Crane at Purdue University in Indiana. Four years later, Peter Mitchell of the University of Edinburgh figured out how coenzyme Q10 produces energy at the cellular level and won the Nobel Prize for chemistry for this discovery in 1978. By the mid-1960s, Japanese researchers recognized that coenzyme Q10 concentrated in the myocardium. In the early 1980s, the first study of coenzyme Q10 was conducted in the treatment of cardiomyopathy. It is currently under investigation for the treatment of neurodegenerative disorders. Although not yet approved by the FDA, the product is available from health food stores. Idebenone, a synthetic analog of coenzyme Q10, has been tested in phase III clinical trials in the treatment of neurodegenerative diseases but has not been approved for use in any of these in the United States. In 2008, Health Canada approved Catena (a proprietary preparation of idebenone) for use in the symptomatic management of patients with Friedreich ataxia based on the promising nature of the clinical evidence. Market authorization was issued with a condition for need of a confirmatory study.

In 2013, the European Medicines Agency (EMA) denied an application originating in Switzerland for the approval of Raxone, a synthetic CoQ10 derivative for Leber hereditary optic neuropathy, because too few patients had been investigated during clinical development; however, there were no safety concerns. Later, this indication was approved by the EMA. In 2007, the FDA granted orphan drug designation to idebenone for the treatment of Duchenne muscular dystrophy, and phase 3 clinical trials were conducted, but approval for this indication was rejected in 2017. An application by the manufacturer for extension of CoQ10 use in patients with Duchenne muscular dystrophy was rejected by the EMA and confirmed after a review in 2018.

Pharmacology

Pharmacodynamics. Coenzyme Q10 serves as the electron acceptor for complexes I and II of the mitochondrial electron transport chain and acts as an antioxidant and is neuroprotective. Water-soluble coenzyme Q10 acts by stabilizing the mitochondrial membrane when neuronal cells are subjected to oxidative stress. It would be an effective plasma antioxidant because it can regenerate plasma vitamin E. Whole-genome sequencing studies have shown that variants in the COQ2 gene, which encodes an enzyme that participates in the synthetic pathway of CoQ10, can be linked to clinically diagnosed multisystem atrophy. Although the role of COQ2 variants in causation of multisystem atrophy remains debatable, data from another study suggest that a deficiency in cerebellar CoQ10 status may be involved in the pathophysiology of this disease (16). Serum CoQ10 can be used as a biomarker in the diagnosis of multisystem atrophy (05). It may be worthwhile to conduct further studies to evaluate the efficacy of CoQ10 in the treatment of multisystem atrophy.

Coenzyme Q10 has the potential to be a beneficial agent in neurodegenerative diseases in which there is impaired mitochondrial function and excessive oxidative damage. The following are some of the effects that have been demonstrated in experimental studies:

In animal models of Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease, coenzyme Q10 can protect against striatal lesions produced by the mitochondrial toxins malonate, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, and 3-nitropropionic acid.

Coenzyme Q10 significantly extended survival in a transgenic mouse model of amyotrophic lateral sclerosis.

Coenzyme Q10 has been shown to ameliorate most of the biochemical changes induced by ischemia/reperfusion in irradiated rat brains.

Pharmacokinetics. Because of its hydrophobicity and large molecular weight, absorption of dietary coenzyme Q10 is slow and limited. Solubilized coenzyme Q10 formulations show enhanced bioavailability with Tmax of approximately 6 hours and an elimination half-life of approximately 33 hours.

Oral preparations of coenzyme Q10 are used in human therapeutics. Various preparations include fast-melting, effervescent, soft gelatin, and powder-filled hard shell. Area under the curve for various formulations is not significantly different. Maximum drug concentration for the various formulations ranges between 0.70 and 0.86 µg/mL. Tmax for the fast-melting and effervescent formulations is 1.3 and 2 hours, respectively. This is significantly shorter compared with the Tmax of soft gel and powder-filled forms, which is 3.7 and 4.1 hours, respectively. Q-Gel, a solubilized form of coenzyme Q10, is superior to tablets and capsules regarding bioavailability. Therefore, lower doses of Q-Gel are required to rapidly reach and maintain adequate blood coenzyme Q10 levels. A colloidal-Q10 preparation using oxa acids improves the intestinal absorption and the bioavailability of coenzyme Q10 (15).

Clinical laboratory monitoring is available for measurement of total coenzyme Q10 in plasma and tissue and for measurement of redox status, ie, the ratio of reduced and oxidized forms of coenzyme Q10. It is recommended that laboratory monitoring should be correlated with effects of treatment.

Indications

CoQ10 is approved for the treatment of Leber hereditary optic neuropathy by the European Medicines Agency, but not the FDA.

Off-label uses

Other uses of coenzyme Q10 are considered investigational. Diseases affecting the retina and brain, such as age-related macular degeneration, glaucoma, Alzheimer disease, and Parkinson disease, have shown defects in cellular biochemical reactions attributed to reduced levels of CoQ10, which can be counteracted through early detection and supplementation, but further research is required (07). Controlled clinical trials have been conducted in neurodegenerative disorders: Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease. Open clinical trials with some beneficial effects include:

	• As a migraine preventive
	• Mitochondrial encephalomyopathies

Potential uses of coenzyme Q10 include:

	• Coenzyme Q10 may be a potential treatment of drug-induced myopathy but has not been tested for this condition. The basis for this is that simvastatin and other HMG-CoA reductase inhibitors have been documented to lower serum concentrations of coenzyme Q10 by blocking the production of an intermediate in the mevalonate pathway that leads to the production of CoQ10. In a clinical study, decreased CoQ10 content in the skeletal muscles was accompanied by a decreased maximal oxidative phosphorylation capacity in the simvastatin-treated patients (06). This finding may explain the muscle pain and exercise intolerance that many patients experience with their statin treatment and provide a new rationale for CoQ10 supplementation. Results of metaanalysis of available randomized controlled trials do not suggest any significant benefit of coenzyme Q10 supplementation in improving statin-induced myopathy (01). Efficacy of CoQ10 supplements in the prevention and treatment of statin-associated muscle symptoms remains controversial, and the effect of oral CoQ10 supplementation in increasing mitochondrial CoQ10 in human skeletal muscle is not well established (20).
	• Administration of coenzyme Q10 combined with mild hypothermia increases survival and can improve neurologic outcome following cardiac arrest and cardiopulmonary resuscitation.
	• Clinical improvement after coenzyme Q10 supplementation has been reported in cerebellar ataxia with coenzyme Q10 deficiency.
	• To reduce the neuropathy caused by the toxic effect of drugs used in the treatment of AIDS
	• High-dose CoQ10 therapy may improve the prognosis of subacute visual impairment in hereditary motor sensory neuropathy type VI (19).
	• A trial of prolonged administration of CoQ10 in Down syndrome reduced oxidative stress, a factor in the progression of neurodegeneration, by modulating DNA repair mechanisms (21).
	• CoQ10 treatment has been shown to restore mitochondrial dysfunction and decreased oxidative stress, which are factors in the pathogenesis of fibromyalgia (03).
	• CoQ10 improves performance during exercise and, thus, may have potential use in management of exercise intolerance and exhaustion in myalgic encephalomyelitis/chronic fatigue syndrome (10). However, a randomized controlled trial showed that CoQ10 does not alleviate the fatigue of the late-onset sequelae of poliomyelitis (12).
	• Results of an open-label study suggests that CoQ10 supplementation might reduce the severity, frequency, and duration of migraine headaches (17).
	• Human glioblastoma cells treated with CoQ10 in vitro have shown 2-fold more sensitivity than control cells to radiation-induced DNA damage as well as potentiation of temozolomide-induced cytotoxicity with no effect on nontreated astrocytes (04). CoQ10 may have value as an adjunct in the treatment of glioblastoma, which should be investigated in a clinical study.
	• A randomized trial is investigating a combination of CoQ10 in combination with meclofenoxate, a cholinergic nootropic drug, for the treatment hepatic encephalopathy associated with liver cirrhosis (NCT03961087).
	• In a randomized controlled trial, CoQ10 was added to standard treatment of sepsis, a condition where CoQ10 levels are decreased and worsening of mitochondrial dysfunction is observed (18). The results suggested that CoQ10 has a positive effect on clinical parameters as well as mitochondrial dysfunction when administered in the early phase of sepsis.

References

01: Banach M, Serban C, Sahebkar A, et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin Proc 2015;90(1):24-34. PMID 25440725
02: Biglan KM, Dorsey ER, Evans RV, et al. Plasma 8-hydroxy-2-deoxyguanosine Levels in Huntington Disease and Healthy Controls Treated with Coenzyme Q10. Journal of Huntington’s Disease 2012;1:73-7. PMID 25063191
03: Cordero MD, Cotán D, del-Pozo-Martín Y, et al. Oral coenzyme Q10 supplementation improves clinical symptoms and recovers pathologic alterations in blood mononuclear cells in a fibromyalgia patient. Nutrition 2012;28(11-12):1200-3. PMID 22898267
04: Frontiñán-Rubio J, Santiago-Mora RM, Nieva-Velasco CM, et al. Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide. Radiother Oncol 2018;128(2):236-44. PMID 29784452
05: Kasai T, Tokuda T, Ohmichi T, et al. Serum levels of coenzyme Q10 in patients with multiple system atrophy. PLoS One 2016;11(1):e0147574. PMID 26812605
06: Larsen S, Stride N, Hey-Mogensen M, et al. Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance. J Am Coll Cardiol 2013;61(1):44-53. PMID 23287371
07: Manzar H, Abdulhussein D, Yap TE, Cordeiro MF. Cellular consequences of coenzyme q10 deficiency in neurodegeneration of the retina and brain. Int J Mol Sci 2020;21(23):9299. PMID 33291255
08: McGarry A, McDermott M, Kieburtz K, et al. A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology 2017;88(2):152-9.** PMID 27913695
09: Montero R, Sánchez-Alcázar JA, Briones P, et al. Analysis of coenzyme Q10 in muscle and fibroblasts for the diagnosis of CoQ10 deficiency syndromes. Clin Biochem 2008;41(9):697-700. PMID 18387363
10: Morris G, Anderson G, Berk M, Maes M. Coenzyme Q10 depletion in medical and neuropsychiatric disorders: potential repercussions and therapeutic implications. Mol Neurobiol 2013;48(3):883-903. PMID 23761046
11: Parkinson Study Group QE3 Investigators, Beal MF, Oakes D, et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol 2014;71(5):543-52. PMID 24664227
12: Peel MM, Cooke M, Lewis-Peel HJ, Lea RA, Moyle W. A randomized controlled trial of coenzyme Q10 for fatigue in the late-onset sequelae of poliomyelitis. Complement Ther Med 2015;23(6):789-93. PMID 26645517
13: Potgieter M, Pretorius E, Pepper MS. Primary and secondary coenzyme Q10 deficiency: the role of therapeutic supplementation. Nutr Rev 2013;71(3):180-8. PMID 23452285
14: Sanoobar M, Eghtesadi S, Azimi A, Khalili M, Jazayeri S, Reza Gohari M. Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with relapsing-remitting multiple sclerosis. Int J Neurosci 2013;123(11):776-82. PMID 23659338
15: Sato Y, Yokoyama S, Yamaki Y, et al. Enhancement of intestinal absorption of coenzyme Q10 using emulsions containing oleyl polyethylene acetic acids. Eur J Pharm Sci 2020;142:105144. PMID 31730802
16: Schottlaender LV, Bettencourt C, Kiely AP, et al. Coenzyme Q10 levels are decreased in the cerebellum of multiple-system atrophy patients. PLoS One 2016;11(2):e0149557. PMID 26894433
17: Shoeibi A, Olfati N, Soltani Sabi M, Salehi M, Mali S, Akbari Oryani M. Effectiveness of coenzyme Q10 in prophylactic treatment of migraine headache: an open-label, add-on, controlled trial. Acta Neurol Belg 2017;117(1):103-9. PMID 27670440
18: Soltani R, Alikiaie B, Shafiee F, Amiri H, Mousavi S. Coenzyme Q10 improves the survival and reduces inflammatory markers in septic patients. Bratisl Lek Listy 2020;121(2):154-8. PMID 32115970
19: Takahashi R, Ikeda T, Hamaguchi A, Iwasa K, Yamada M. Coenzyme Q10 therapy in hereditary motor sensory neuropathy type VI with novel mitofusin 2 mutation. Intern Med 2012;51(7):791-3. PMID 22466841
20: Taylor BA. Does coenzyme Q10 supplementation mitigate statin-associated muscle symptoms? Pharmacological and methodological considerations. Am J Cardiovasc Drugs 2018;18(2):75-82. PMID 29027135
21: Tiano L, Padella L, Santoro L, et al. Prolonged coenzyme Q10 treatment in Down syndrome patients: effect on DNA oxidation. Neurobiol Aging 2012;33(3):626.e1-8. PMID 21601315
22: Yamagishi K, Ikeda A, Moriyama Y, et al. Serum coenzyme Q10 and risk of disabling dementia: the Circulatory Risk in Communities Study (CIRCS). Atherosclerosis 2014;237(2):400-3. PMID 25463064

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Coenzyme Q10

Also Relevant

Amyotrophic lateral sclerosis
Ataxia
Complex II deficiency
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Huntington disease
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- Leber hereditary optic neuropathy
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- Migraine
- Neuropharmacology
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- Parkinson disease
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Coenzyme Q10

Coenzyme Q10

Introduction

Historical note and terminology

Pharmacology

Clinical trials

Indications

Off-label uses

Contraindications

Goals and duration of treatment

Dosing

Special considerations

Interactions

Adverse effects

References

Contributors

Author

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Neurogenetics and genetic and genomic testing

Acute traumatic spinal cord injury

Tumors of the skull base

Toxic and nutritional deficiency optic neuropathies

Third nerve palsy

Nystagmus

Brain death/death by neurologic criteria

Outpatient rehabilitation of chronic neurologic conditions

Coenzyme Q10

Introduction

Historical note and terminology

Pharmacology

Clinical trials

Indications

Off-label uses

Contraindications

Goals and duration of treatment

Dosing

Special considerations

Interactions

Adverse effects

References

Contributors

Author

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Neurogenetics and genetic and genomic testing

Acute traumatic spinal cord injury

Tumors of the skull base

Toxic and nutritional deficiency optic neuropathies

Third nerve palsy

Nystagmus

Brain death/death by neurologic criteria

Outpatient rehabilitation of chronic neurologic conditions

This is an article preview.
Start a Free Account
to access the full version.