Mitochondrial energy production is impaired in people suffering from recurrent migraines.1 2 This impairment appears to play a role in the pathogenesis of migraines, since two different nutrients that are essential for mitochondrial energy production (i.e., riboflavin3 and magnesium4 ) were each shown in randomized controlled trials in the 1990s to be effective for migraine prophylaxis. The effectiveness of riboflavin and magnesium led researchers to investigate whether Coenzyme Q10 (CoQ10) would also be beneficial. As a component of the electron-transport chain, CoQ10 is also essential for mitochondrial energy production. Below is a brief review of the clinical trials that have been published to date on CoQ10.

 

Randomized, placebo-controlled trials


Forty-two migraine patients (mean age, 39 years) were randomly assigned to receive, in double-blind fashion, 100 mg of CoQ10 3 times per day or placebo for 4 months. The primary outcome measure was the change in attack frequency in month 4 compared with baseline. The proportion of patients who had a 50%-or-greater reduction in attack frequency in month 4 compared with baseline was significantly higher in the CoQ10 group than in the placebo group (47.6% vs. 14.3%; p = 0.02).5

Eighty-four patients (mean age, 34 years) with episodic migraine were randomly assigned to receive, in double-blind fashion, 400 mg per day of CoQ10 or placebo for 12 weeks. Compared with placebo, CoQ10 significantly decreased the mean frequency, severity, and duration of migraines (p < 0.001 for each comparison).6

Fifty patients (mean age, 32 years) with episodic migraine were randomly assigned to receive, in double-blind fashion, 100 mg of CoQ10 3 times per day or placebo for 8 weeks. Compared with placebo, CoQ10 had no significant effect on the frequency, severity, or duration of migraines, although there was a nonsignificant trend in favor of CoQ10.7

One hundred twenty children and adolescents with recurrent migraines were randomly assigned to receive, in double-blind fashion, 100 mg per day of CoQ10 or placebo for 16 weeks and were then switched to the other treatment (CoQ10 or placebo) for an additional 16 weeks. Significant improvements were seen both with CoQ10 and with placebo, but there was no significant difference between treatments.8

 

kids headache

 

Uncontrolled trials

Thirty-two adults with episodic migraine received 150 mg of CoQ10 per day for 3 months. During the last two treatment months, 61.3% of patients had a greater-than-50% reduction in the number of days with migraine (compared with baseline).9

Forty adults with episodic migraine were randomly assigned to receive 300 mg or 600 mg per day of CoQ10 for 3 months. Sixty-three percent of the patients had a reduction of more than 50% in the frequency and intensity of migraines, and 25% of patients had a reduction of more than 50% in the intensity but not the frequency of migraines.

Forty adults with at least 4 migraines per month who had been receiving medications for migraine prophylaxis were assigned (without randomization) to receive 100 mg of CoQ10 per day or no CoQ10 for 3 months, while continuing their medications. Compared with the group that did not receive CoQ10, the group that received CoQ10 had a significant decrease in the frequency and severity of migraines.11

Five hundred ten children and adolescents received CoQ10 at a dose of 1 to 3 mg per kg per day for a mean duration of 97 days. The mean number of headache days per month decreased by 35% compared with baseline (p < 0.001).12

 

CoQ10 used in combination with other treatments

Fifty-six adults with recurrent migraines received the combination of 30 mg per day of CoQ10 and 500 mg per day of L-carnitine or placebo for 8 weeks. Compared with placebo, CoQ10/L-carnitine significantly decreased the frequency, severity, and duration of migraines.13

One hundred thirty adults (mean age, 38 years) with at least 3 migraines per month were randomly assigned to receive, in double-blind fashion, a daily proprietary nutritional supplement or placebo for 3 months. The supplement provided 400 mg of riboflavin, 600 mg of magnesium, 150 mg of CoQ10, and a multivitamin with trace minerals. Patients rated the nutritional supplement as significantly more effective than placebo (p = 0.01).14

 

Discussion

Three randomized trials in adults compared CoQ10 (300 to 400 mg per day) with placebo. In 2 of those trials, CoQ10 was significantly more effective than placebo for migraine prophylaxis. In the other trial, CoQ10 was nonsignificantly more effective than placebo. CoQ10 was not beneficial in the one randomized study of children and adolescents.

In 3 uncontrolled trials, CoQ10 in doses of 100 to 600 mg per day was beneficial for migraine prophylaxis in adults. In an uncontrolled trial in children, CoQ10 at a dose of 1 to 3 mg per kg per day was also effective for migraine prophylaxis. Because there is a substantial placebo effect in many migraine prophylaxis studies, the results of the uncontrolled trials should be viewed with caution.

In 2 trials, CoQ10 was given in combination with other compounds. In one of these trials, the combination of 30 mg per day of CoQ10 and 500 mg per day of L-carnitine was effective. However, because 500 mg per day of L-carnitine when administered as monotherapy has also been shown in a randomized trial to prevent migraines,15 it is not clear to what extent, if any, CoQ10 contributed to the beneficial effect observed in the CoQ10/L-carnitine study. In the other trial, the daily combination of 400 mg of riboflavin, 600 mg of magnesium, 150 mg of CoQ10, and other ingredients was beneficial. However, 600 mg per day of magnesium when given alone, and 400 mg per day of riboflavin when given alone have each been shown in double-blind trials to be effective for migraine prophylaxis.3 4 Therefore, it is not clear whether the addition of CoQ10 to magnesium and riboflavin provided any additional benefit.

Conclusion

The results of randomized placebo-controlled trials indicate that CoQ10 in dosages of 300 to 400 mg per day is effective for migraine prophylaxis. To date there are no published randomized placebo controlled studies showing that CoQ10 as a monotherapy in dosages less than 300 mg per day is of value for migraine prophylaxis. Dosages less than 300 mg per day were found to be beneficial in some uncontrolled trials, but the possibility of a placebo effect cannot be ruled out. In addition, it is unclear whether the addition of CoQ10 in dosages less than 300 mg per day could increase the efficacy of treatments such as magnesium and riboflavin.

References

1 Lodi R, Montagna P, Soriani S, et al. Deficit of brain and skeletal muscle bioenergetics and low brain magnesium in juvenile migraine: an in vivo 31P magnetic resonance spectroscopy interictal study. Pediatr Res 1997;42:866-871.

2 Okada H, Araga S, Takeshima T, Nakashima K. Plasma lactic acid and pyruvic acid levels in migraine and tension-type headache. Headache 1998;38:39-42.

3 Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998;50:466-470.

4 Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 1996;16:257-263.

5 Sandor PS, Di Clemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology 2005;64:713-715.

6 Dahri M, Hashemilar M, Asghari-Jafarabadi M, Tarighat-Esfanjani A. Efficacy of coenzyme Q10 for the prevention of migraine in women: a double-blind, placebo-controlled study. Eur J Integrative Med 2017;16:8-14. Note: Preliminary data from this same study were presented in two other papers: Dahri M, Tarighat-Esfanjani A, Asghari-Jafarabadi M, Hashemilar M. Oral coenzyme Q10 supplementation in patients with migraine: Effects on clinical features and inflammatory markers. Nutr Neurosci 2019;22:607-615.; and Nattagh-Eshtivani E, Dahri M, Hashemilar M, Tarighat-Esfanjani A. The effect of coenzyme Q10 supplementation on serum levels of lactate, pyruvate, matrix metalloproteinase 9 and nitric oxide in women with migraine. A double blind, placebo, controlled randomized clinical trial. Eur J Integrative Med 2018;21:70-76.

7 Parohan M, Sarraf P, Javanbakht MH, et al. The synergistic effects of nano-curcumin and coenzyme Q10 supplementation in migraine prophylaxis: a randomized, placebo-controlled, double-blind trial. Nutr Neurosci 2021;24:317-326.

8 Slater SK, Nelson TD, Kabbouche MA, et al. A randomized, double-blinded, placebo-controlled, crossover, add-on study of coenzyme Q10 in the prevention of pediatric and adolescent migraine. Cephalalgia 2011;31:897-905.

 9 Rozen TD, Oshinsky ML, Gebeline CA, et al. Open label trial of coenzyme Q10 as a migraine preventive. Cephalalgia 2002;22:137-141.

10 Dalla Volta G, Carli D, Zavarise P, et al. P026. Pilot study on the use of coenzyme Q10 in a group of patients with episodic migraine without aura. J Headache Pain 2015;16(Suppl 1):A186.

11 Shoeibi A, Olfati N, Soltani Sabi M, et al. Effectiveness of coenzyme Q10 in prophylactic treatment of migraine headache: an open-label, add-on, controlled trial. Acta Neurol Belg 2017;117:103-109.

12 Hershey AD, Powers SW, Vockell AL, et al. Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. Headache 2007;47:73-80.

13 Hajihashemi P, Askari G, Khorvash F, et al. The effects of concurrent Coenzyme Q10, L-carnitine supplementation in migraine prophylaxis: A randomized, placebo-controlled, double-blind trial. Cephalalgia 2019;39:648-654.

14  Gaul C,  Diener HC, Danesch U, et al. Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial. J Headache Pain 2015;16:32.

15 Tarighat Esfanjani A, Mahdavi R, Ebrahimi Mameghani M, et al. The effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation in migraine prophylaxis. Biol Trace Elem Res 2012;150:42-48