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.

Clinical trials

A randomized, double-blind, placebo-controlled trial on patients with Parkinson disease using doses of 1200 mg/day or 2400 mg/day of CoQ10 showed no adverse effects, but there was no evidence of clinical benefit (11).

In the open-label clinical trial known as Pre-2Care, Huntington disease patients and healthy controls were given CoQ10 daily for 20 weeks (02). Serum 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative stress due to mitochondrial dysfunction that is elevated in Huntington disease, was reduced by 20% along with symptomatic improvement.

A randomized, double-blinded, placebo-controlled trial has shown that CoQ10 supplements at a dose of 500 mg/day can decrease oxidative stress and increase antioxidant enzyme activity in patients with relapsing-remitting multiple sclerosis (14). Effect on the course of the disease was not studied.

A multicenter randomized, double-blind, placebo-controlled trial has shown that use of high dose CoQ10 for 60 months did not slow functional decline in Huntington disease (08).

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:

Potential uses of coenzyme Q10 include:

Contraindications

None identified yet.

Goals and duration of treatment

The aim of coenzyme Q10 therapy is neuroprotection and slowing the progression of neurodegenerative disorders. For these indications, long-term therapy is anticipated. If the decision to use coenzyme Q10 is based on deficiency of the enzyme, this can be determined in both muscle and fibroblasts by biochemical methods (09). Primary deficiency has been well described and results from mutations in genes involved in CoQ10 biosynthesis (13). A case-control study in Japan has shown that serum coenzyme Q10 levels are inversely associated with risk of disabling dementia (22).

Dosing

Therapeutic dosages of coenzyme Q10 for serious diseases range from 200 to 400 mg. Preventive dose ranges from 10 to 30 mg daily as recommended by various manufacturers.

Coenzyme Q10 has been used safely at a dosage of 2400 mg/day in clinical trials on Huntington disease patients and up to 3000 mg/day on patients with amyotrophic lateral sclerosis.

Special considerations

Pediatric. No use has been reported in the pediatric population.

Geriatric. No special precautions.

Pregnancy. The normal curve of plasma coenzyme Q10 levels rises during each trimester of pregnancy, and an association between low coenzyme Q10 level and spontaneous abortion has been observed. Maternal coenzyme Q10 plasma levels can be considered as a biomarker of pathological uterine contractile activity. There is a substantial increase in coenzyme Q10 fetal plasma levels in fetuses affected by hypoxic hypoxia and in those affected by nonimmune fetal hydrops.

Coenzyme Q10 has been incorporated in multivitamin/mineral supplement during pregnancy and no complications have been reported from this use.

Anesthesia. No interaction has been reported between anesthetics and coenzyme Q10.

Interactions

Interactions of coenzyme Q10 with other drugs have not been reported. Interaction with warfarin is well known.

Adverse effects

No serious adverse events have been reported with coenzyme Q10. Gastrointestinal disturbances have been reported after oral intake of large doses of coenzyme Q10.