Further Evidence that Mitochondrial Dysfunction May Play a Critical Role With Migraine Pathogenesis

Abstract & Commentary

Commentary by M. Flint Beal, MD, Professor and Chairman, Department of Neurology, Cornell University Medical College, New York, NY, Editor, Neurology Alert.

Synopsis: CoQ10 significantly reduced the number of days with migraine attacks and significantly reduced in the number of days with nausea.

Source: Sandor PS, et al. Efficacy of Coenzyme Q10 in Migraine Prophylaxis: A Randomized, Controlled Trial. Neurology. 2005;64:713-715.

There is a substantial body of evidence, using 31 phosphorous NMR spectroscopy, that there are abnormalities in brain energy metabolism in migraine. This has been reported by at least 2 or 3 investigators. In addition, elevation of cerebral lactate has also been reported in migraine during the inter-ictal period. Further evidence in favor of the potential role of mitochondrial dysfunction in migraine is the observation that patients with MELAS syndrome have increased migraine headaches. This is caused by a mitochondrial transfer-RNA leucine mutation. In a previous controlled clinical trial, riboflavin produced a significant beneficial effect in preventing migraine headaches (Schoenen, et al. 1998).

In the present trial, Sandor and colleagues carried out a doubleblind, controlled clinical trial of coenzyme Q10 (CoQ10) for migraine prophylaxis. They examined CoQ10 administered as 100 mg 3 times a day, as compared to placebo in 42 migraine patients. Patients were examined with placebo for a 1-month baseline. On the second visit, they were randomized to CoQ10 or placebo if they had at least 1 migraine attack in the preceding month. The primary outcome variable was change in attack frequency by month 4, as compared with baseline. Secondary outcome variables included reduction in migraine days, mean headache duration per day, mean severity per day, and days with nausea and vomiting. Sandor et al observed that CoQ10 significantly reduced the number of days with migraine attacks. This became apparent at the 1, 2, and 3 month after time points. This was a significant effect. In addition, the 50% responder rate for headache frequency was higher in patients treated with CoQ10 than with placebo. The response rate was 47.6% for CoQ10 treated patients, as compared to 14.4% for placebo. This rate in the placebo group is comparable to that previously observed in other clinical trials. Sandor et al also found that there was a significant reduction in the number of days with nausea in the patients treated with CoQ10.

Commentary

As noted above, there is substantial evidence that there may be links between mitochondrial dysfunction and migraine headaches. Mitochondrial dysfunction may result in increased membrane excitability, which could lead to spreading cortical depolarization response. The spreading cortical depolarization of Leão has been linked to migraine aura. One would expect that it might be more readily activated in patients who had reduced membrane potential due to mitochondrial defects.

This is the second control trial which shows that administration of agents, which can improve mitochondrial function, may have activity in preventing migraine headaches. This is certainly an area which needs further investigation. Administration of CoQ10 is associated with virtually no side effects of the doses utilized in the present study. Similarly, riboflavin treatment is relatively benign. This, therefore, might lead to a new treatment for migraines, which would be relatively free of side effects. CoQ10 is an excellent candidate for children or women of child bearing age due to its excellent tolerability.