Thirty-two patients (26 women, 6 men) with a history of episodic migraine with or without aura were treated with coenzyme Q10 at a dose of 150 mg per day. Thirty-one of 32 patients completed the study; 61.3% of patients had a greater than 50% reduction in number of days with migraine headache. The average number of days with migraine during the baseline period was 7.34 and this decreased to 2.95 after 3 months of therapy, which was a statistically significant response.

Mean reduction in migraine frequency after 1 month of treatment was 13.1% and this increased to 55.3% by the end of 3 months. Mean migraine attack frequency was 4.85 during the baseline period and this decreased to 2.81 attacks by the end of the study period, which was a statistically significant response (P<0.001).

There were no side-effects noted with coenzyme Q10. From this open label investigation coenzyme Q10 appears to be a good migraine preventive.

Rozen TD, Oshinsky ML, Gebeline CA, Bradley KC, Young WB, Shechter AL & Silberstein SD. Open label trial of coenzyme Q10 as a migraine preventive. Cephalalgia 2002; 22:137–141. London. ISSN 0333-1024

Introduction

At present there are very few efficacious migraine preventives and fewer without significant side-effects. In medicine there has been a trend towards the developmentof natural therapies that can be safely taken by all who suffer with a disease regardless of age and past medical history.

Migraine in particular is a disorder of young people and this patient population is very resistant to taking any form of medication, especially when it needs to be used on a daily basis. Migraine can be a disabling disorder and migraine preventives have been shown to not only reduce headache frequency, intensity and duration but also improve quality of life.

Coenzyme Q10 is a naturally occurring substance and essential element of the mitochondrial electron transport chain. It has been the most extensively studied agent for

the treatment of mitochondrial disorders and has been shown to have almost no identifiable side-effects in humans.

There has been a recent interest in the role that mitochondria may play in migraine pathogenesis. Clues from magnetic resonance spectroscopy (1) studies and DNA analysis (2) suggest that migraine, at least in a subset of individuals, may be the result of mitochondrial impairment. If indeed migraine results from mitochondrial dysfunction, then coenzyme Q10 could be used as a successful migraine preventive.

The objective of this investigation is to assess the efficacy of coenzyme Q10 as a preventive treatment for migraine headaches.

Coenzyme Q10

Coenzyme Q10 is an essential element of the mitochondrial electron transport chain. It is a naturally occurring, small hydrophobic substance, that freely moves throughout the inner mitochondrial membrane transferring electrons from the NADH dehydrogenase complex (complex I) and the succinate-Q-reductase complex (complex II) to cytochrome C.

In addition to its actions as an electron carrier, coenzyme Q10 may also act as an antioxidant and help protect the myocardium from post-ischaemic re-perfusion injury.

The treatment of mitochondrial cytopathies has focused on improving defects in respiratory metabolism. 

Coenzyme Q10 has been the most extensively studied agent in this setting. Coenzyme Q10 therapy has led to improvement of cardiac conduction defects in a patient with Kearns–Sayre syndrome. Muscle weakness and fatigue has been improved in patients with chronic muscular dystrophies and neurogenic atrophies after coenzyme Q10 therapy. Coenzyme Q10 administration has improved exercize tolerance, strengthened muscle weakness, lowered serum pyruvate and lactate levels, and quickened post-exercize recovery of phosphocreatine in patients with mitochondrial encephalomyopathies.

Exogenous coenzyme Q10 also appears to act on the central nervous system directly by causing a marked reduction in CSF lactate and pyruvate levels, as well as an improvement in somatosensory evoked potential latencies in patients with mitochondrial cytopathies.

Iimprovement in both brain and muscle energy metabolism after coenzyme Q10 administration has been obsereved.

Coenzyme Q10 has not only been used in the treatment of mitochondrial disorders, but has also found success in the treatment of chronic congestive heart failure and as an aid for myocardial preservation in patients undergoing cardiac surgery. Coenzyme Q10 can be administered orally or parenterally. Peak blood levels occur 5–10 h after oral

administration. Elimination half-life is 34 h.

Endogenous coenzyme Q10 levels normally range from 0.7 to 1 mcg/ml and can usually be increased to two times normal levels with oral doses of 200 mg per day. Coenzyme Q10 administration has been very well tolerated in doses up to 2400 mg per day, with an excellent side-effect profile.

The most common side-effects pertain to the gastrointestinal system and include nausea, diarrhoea, appetite suppression, heartburn and epigastric discomfort. In large studies the incidence of gastrointestinal side-effects is less than 1%.

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Discussion

There has been a recent explosion in the number of new migraine abortive treatments but novel, safe and efficacious migraine preventive therapies have been lacking.Knowledge about migraine pathogenesis has helped in the development of the triptans and a better understanding of migraine pathophysiology will lead to the discovery of newer preventives. There has been recent interest in the role that mitochondria may play in migraine pathogenesis. It is clear from MRS studies that at least a subset of migraineurs have a dysfunction in mitochondrial energy metabolism. Coenzyme Q10 has been shown to improve mitochondrial oxidative phosphorylation in humans. If mitochondrial dysfunction is

playing a role in migraine genesis then coenzyme Q10 could improve mitochondrial function and thus prevent migraine headaches. This belief is not without precedence as riboflavin, in an open label pilot study and a placebo controlled trial has been shown to reduce migraine frequency.

Riboflavin is indirectly involved in the electron transport chain as a precursor of flavin mononucleotides. Coenzyme Q10 is an essential element of the electron transport chain, suggesting that it could also work as a migraine preventive. From this open-label investigation coenzyme Q10 appears to be a good migraine preventive.

Over 60% of coenzyme Q10-treated patients had a greater than 50% reduction in number of days with migraine headache.

Our data suggest that coenzyme Q10 starts to work within 4 weeks of initiation of therapy (mean reduction in days with migraine was 13.1% after 1 month of therapy) but usually takes 5 to 12 weeks to yield a greater than 50% reduction in days with migraine (by the end of 3 months of therapy mean reduction in days with migraine was 55.3%). From this small sample population coenzyme Q10 appears to work equally well in migraineurs with and without a history of aura.

A very important finding from this open label study is that coenzyme Q10 administration appears to be associated with no significant adverse events and is extremely well-tolerated. Dose ranging studies lwould be useful. Higher doses of coenzyme Q10 (up to 3000 mg) have been utilized in mitochondrial encephalomyopathy patients without adverse events, so dosages above 150 mg may yield even higher 50% reduction rates than was demonstrated in this study.

Coenzyme Q10 looks to be an excellent choice for initial

therapy for prevention of episodic migraine if confirmed

by controlled studies of efficacy. It can be given to almost

any age group without fear of significant side-effects.