Is CoQ10 Beneficial for Mitochondrial Muscle Disorders?

Abstract & Commentary

By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports no financial relationships relevant to this field of study.

Synopsis: In this small clinical trial, supplementation with CoQ 10 did not result in any clinical improvement for patients with mitochondrial disorders.

Source: Glover EI, et al. A randomized trial of coenzyme Q10 in mitochondrial disorders. Muscle Nerve 2010;42:739-748.

Located in the inner mitochondrial membrane, coenzyme Q10, (CoQ10) is a mitochondrial respiratory chain electron carrier whose absence disrupts the flow of electrons from complexes I and II to complex III. Safe and free of any significant adverse side effects, supplementation with CoQ10 may be beneficial in primary CoQ10 deficiency1 but its role in other mitochondrial disorders has not been studied previously in randomized clinical trials.

Glover et al enrolled 30 patients with mitochondrial cytopathy, including mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS, n = 15, 6 males, 9 females); chronic progressive external encephalopathy (CPEO, n = 11, 4 males, 7 females); and 1 patient each with mitochondrial myopathy due to complex I deficiency; neuropathy, ataxia, and retinitis pigmentosa (NARP); ataxia-neuropathy; and Leber's hereditary optic neuropathy (LHON). Subjects were recruited from the McMaster University Neuromuscular/Neurometabolic Clinic and enrolled in a randomized, double-blind, crossover trial to determine the efficacy of 1,200 mg CoQ10/day for 60 days. Diagnosis was confirmed by clinical symptomatology, fasting serum lactate levels, muscle biopsy, and mitochondrial DNA analysis. Outcome measures included urinary analysis for oxidative stress markers (creatinine, 8-isoprostane, 8-hydroxy-2-deoxyguanosine), whole blood lactate level, plasma CoQ10 concentration, forearm isometric fatigue test, near-infrared spectroscopy, dual-energy X-ray absorptiometry, cycle ergometry testing, magnetic resonance spectroscopy, quality of life, and activities of daily living. Statistical analysis comprised the paired t-test and Tukey's post hoc test, and P < 0.05 was considered significant.

Oral administration of CoQ10 raised blood CoQ10 concentrations, but other blood and urine measures were unchanged. No significant differences were appreciated between treatment phases with the forearm isometric fatigue test, post-exercise lactate level, near-infrared spectroscopy, or cycle ergometry at 5 minutes. At 15 minutes, VO2 was increased, and lactate rise was attenuated, in the CoQ10 group. Magnetic resonance spectroscopy was comparable in both groups, but grey matter choline-containing compound measurements were lower during CoQ10 treatment. Responses to questionnaires regarding quality of life and activities of daily living were similar between both groups. In this trial, CoQ10 supplementation produced no tangible clinical benefit in patients with mitochondrial cytopathy.

Commentary

Although CoQ10 appears to lack clinical efficacy for mitochondrial cytopathy in this study, all hope is not lost. Exercise training, including both resistance and endurance training, appears to benefit patients with mitochondrial myopathies. Intravenous L-arginine, a nitric oxide donor, may attenuate stroke-like episodes in MELAS by inducing vasodilatation. Cysteine donor supplementation will reduce oxidative stress levels but, like CoQ10, do not modify lactate concentration, clinical scale, or quality of life. Preliminary studies indicate that increased ketone bodies lead to increased mitochondrial biogenesis, supporting the notion that a ketogenic diet, high in lipids and low in glucose, may be beneficial. Lastly, activation of the peroxisome proliferator-activated receptor (PPAR/PGC-1a) pathway may increase mitochondrial biogenesis and perhaps holds the most promise for future research.2

References

1. Montini G, et al. Early coenzyme Q10 supplementation in primary coenzyme Q10 deficiency. N Engl J Med 2008;358: 2849-2850.

2. Hassani A, et al. Mitochondrial myopathies: developments in treatment. Curr Opin Neurol 2010;23;459-465.