CoQ10 for Migraine Prevention

Table of Contents

1. Migraine and Brain Energy Metabolism
2. Cortical Spreading Depression & the Energy Reserve Hypothesis
3. CoQ10 Levels in Migraine Patients
4. The Sandor 2005 Trial
5. Children: the Hershey 2007 Series and the Slater 2011 Trial
6. The Meta-Analyses: Parohan 2020, Zeng 2019 and Okoli 2019
7. The Sazali 2021 Meta-Analysis and Two Add-On Trials
8. The 2012 AAN / AHS Guideline (Retired in 2015)
9. CoQ10, Riboflavin and Magnesium: the Related Trials
10. Doses Used in the Trials
11. Combinations With Conventional Migraine Preventives
12. Common Questions
13. Cautions
14. Key Research Papers
15. Connections
16. Featured Videos

Migraine and Brain Energy Metabolism

Migraine research has moved away from the older idea of migraine as mainly a disorder of blood vessels toward a view of migraine as a disorder of the brain itself, with altered excitability of the cortex. One line of this research concerns energy metabolism. In a 1995 review, Welch and Ramadan summarized evidence for disordered mitochondrial oxidative phosphorylation and reduced intracellular free magnesium in the brain and body tissue of people with migraine, both between and during attacks, and proposed that these metabolic shifts make neurons less stable between attacks and so make the brain more susceptible to an attack.

This is the reasoning behind trials of CoQ10 and riboflavin: both take part in the mitochondrial respiratory chain. Riboflavin supplies the FMN cofactor of Complex I and the FAD cofactor of Complex II, and CoQ10 carries electrons from Complexes I and II to Complex III. Magnesium is studied for migraine for related reasons; ATP is biologically active largely as a magnesium-ATP complex. Whether raising CoQ10 intake raises the energy reserve of brain cells in people with migraine has not been shown directly; the trials measured headache outcomes, not brain energy metabolism.

Back to Table of Contents

Cortical Spreading Depression & the Energy Reserve Hypothesis

Cortical spreading depression (CSD) is a slowly spreading wave of depolarization of brain cells followed by a period of suppressed electrical activity. It was first described in detail by Leão in 1944. A 2009 review by Charles and Brennan notes that recent reports of CSD in people with brain injury show that it occurs in the human brain, that astrocytes and blood vessels may play an active role in it, and that animal studies of CSD can inform migraine research — but also that the exact role of CSD in migraine has not been conclusively established.

The "energy reserve" hypothesis links these ideas. In outline, it holds that:

1. migraine brains have a reduced mitochondrial energy reserve;
2. triggers raise energy demand toward that ceiling;
3. when demand outstrips supply, the brain becomes more susceptible to an attack, possibly through CSD;
4. a treatment that improves mitochondrial energy production would, if the hypothesis is right, make attacks less likely.

The last step is the basis on which CoQ10 was tested; Sandor's trial was designed on the reasoning that riboflavin, which improves energy metabolism in a similar way, had been effective. The trial results below are the test of that reasoning, and they are mixed.

Back to Table of Contents

CoQ10 Levels in Migraine Patients

The largest measurement of CoQ10 in people with migraine comes from the Cincinnati Children's Hospital headache center (Hershey et al. 2007). CoQ10 was measured in 1,550 children, adolescents and young adults (mean age 13.3, range 3 to 22) attending the center with frequent headaches. The mean total CoQ10 level was 0.60 µg/mL, and 32.9% of patients were below the reference range. The authors concluded that CoQ10 deficiency "may be common" in pediatric and adolescent migraine. The study had no healthy comparison group, so it does not show whether low levels are more common in migraine than in other children.

Similar figures for adults, and figures for riboflavin and magnesium deficiency in migraine, are often quoted, but no verified source for them is cited on this page.

Back to Table of Contents

The Sandor 2005 Trial

Sándor and colleagues, at the Headache and Pain Unit of University Hospital Zurich, published the first randomized, placebo-controlled trial of CoQ10 for migraine prevention in 2005 in Neurology.

Design

• 42 people with migraine, randomized double-blind to CoQ10 100 mg three times daily (300 mg/day) or placebo
• Outcomes were compared in the third month of treatment

Results (as reported in the abstract)

• CoQ10 was superior to placebo for attack frequency, headache days and days with nausea in the third treatment month
• The 50%-responder rate for attack frequency (the share of patients whose attacks fell by at least half) was 47.6% with CoQ10 and 14.4% with placebo; the number needed to treat was 3
• CoQ10 was well tolerated

With 42 participants, the trial is small, and its result has not been repeated in a trial of similar design and larger size.

Back to Table of Contents

Children: the Hershey 2007 Series and the Slater 2011 Trial

Hershey et al. 2007 (Headache) — an uncontrolled series

The Cincinnati study described above was not a randomized trial and had no placebo group. Patients found to have low CoQ10 were advised to start 1 to 3 mg/kg per day of CoQ10 as part of their multidisciplinary treatment plan. In the subset who returned for timely follow-up (after a mean of 97 days):

• total CoQ10 rose from 0.60 to 1.20 µg/mL
• headache frequency fell from 19.2 to 12.5 (P < .001)
• headache disability on the PedMIDAS scale fell from 47.4 to 22.8 (P < .001)

Because there was no control group and supplementation was one part of a wider treatment plan, the improvement cannot be attributed to CoQ10. The authors wrote that "more scientifically rigorous methodology will be required to confirm this observation."

Slater et al. 2011 (Cephalalgia) — the randomized pediatric trial

The same Cincinnati group then ran that more rigorous study: a randomized, double-blind, placebo-controlled crossover trial in 120 children and adolescents with migraine, who received CoQ10 100 mg/day or placebo added to standard treatment for 224 days. Data were available for 76 patients at the crossover point and 50 were analysed at the end.

• Both the CoQ10 and the placebo groups had fewer, less severe and shorter migraines over time
• There was no difference in headache outcomes between CoQ10 and placebo at day 224
• CoQ10 patients improved faster in the first 4 weeks; the authors note that, given the sample size, this needs further investigation

The authors concluded that the children improved with multidisciplinary, standardized treatment "regardless of supplementation with CoQ10 or placebo." This trial, not the 2007 series, is the controlled pediatric evidence.

Back to Table of Contents

The Meta-Analyses: Parohan 2020, Zeng 2019 and Okoli 2019

Several meta-analyses have pooled the CoQ10 migraine trials. They draw on largely the same small set of trials but chose them differently, and they reach different conclusions.

Parohan et al. 2020 (Nutritional Neuroscience)

• 4 randomized trials, 221 participants, searched to April 2018
• Attack frequency: 1.87 fewer attacks a month with CoQ10 (weighted mean difference −1.87; 95% CI −2.69 to −1.05; p < 0.001)
• Severity: no significant effect (−2.35 on a visual analog scale; 95% CI −5.19 to 0.49; p = 0.105)
• Duration: no significant effect (−6.14 hours; 95% CI −13.14 to 0.87; p = 0.086), with high heterogeneity

The authors concluded that CoQ10 "may reduce the frequency of migraine attacks per month without affecting the severity or duration of migraine attacks."

Zeng et al. 2019 (Acta Neurologica Scandinavica)

• 5 studies, 346 patients (120 pediatric and 226 adult)
• CoQ10 did not differ significantly from placebo in migraine attacks a month (P = 0.08) or severity (P = 0.08)
• CoQ10 reduced migraine days a month (P < 0.00001) and migraine duration (P = 0.009)

Okoli et al. 2019 (Canadian Journal of Neurological Sciences)

This review of vitamins and minerals for migraine prevention included 18 placebo-controlled trials. For CoQ10 in adults, only 2 trials (97 participants) could be pooled, and CoQ10 did not significantly reduce migraine frequency (mean difference −0.44; 95% CI −2.14 to 1.26), duration or severity. The authors concluded that, "based on insufficient evidence, it is unknown if coenzyme Q10 and magnesium are effective for migraine prophylaxis in adults."

Pooled attack-frequency results as reported in each meta-analysis abstract; Zeng 2019 reports only a P value for this outcome.

Back to Table of Contents

The Sazali 2021 Meta-Analysis and Two Add-On Trials

Sazali and colleagues published a meta-analysis limited to adults in 2021 in BMJ Open, searching to December 2019. It included randomized trials comparing CoQ10 with placebo or as an add-on treatment, and excluded crossover designs.

• 6 studies, 371 participants
• Severity: no statistically significant reduction
• Duration: reduced (mean difference −0.19; 95% CI −0.27 to −0.11; I² = 0%)
• Frequency: reduced (mean difference −1.52; 95% CI −2.40 to −0.65; I² = 0%)

The authors concluded that CoQ10 "appears to have beneficial effects in reducing duration and frequency of migraine attack."

Two add-on trials in adults

• Shoeibi et al. 2017 (Acta Neurologica Belgica) — an open-label (not blinded, no placebo) controlled trial in 80 adults, matched rather than randomized, comparing current preventive drugs alone with the same drugs plus CoQ10 100 mg daily. Of the 36 and 37 patients analysed, attacks a month fell by 1.6 with CoQ10 and 0.5 without (p < 0.001) and severity by 2.3 vs 0.6; the number needed to treat for a 50% fall in attacks was 1.6.
• Dahri et al. 2019 (Nutritional Neuroscience) — a randomized, double-blind, placebo-controlled trial in 45 women aged 18-50 with episodic migraine, all also on preventive medication, given CoQ10 400 mg/day (23 women) or placebo (22) for three months. Frequency, severity and duration of attacks improved more with CoQ10, and blood levels of CGRP and TNF-α fell; IL-6 and IL-10 did not differ between groups.

Back to Table of Contents

The 2012 AAN / AHS Guideline (Retired in 2015)

The 2012 evidence-based guideline of the American Academy of Neurology and the American Headache Society on NSAIDs and complementary treatments for episodic migraine prevention in adults (Holland et al.) reviewed studies published from June 1999 to May 2009 and graded:

• Level A (effective): butterbur (Petasites)
• Level B (probably effective): fenoprofen, ibuprofen, ketoprofen, naproxen, naproxen sodium, a feverfew extract, magnesium, riboflavin and subcutaneous histamine
• Level C (possibly effective): cyproheptadine, CoQ10, estrogen, mefenamic acid and flurbiprofen
• Conflicting or inadequate data: aspirin, indomethacin, omega-3 and hyperbaric oxygen

The guideline has been retired. According to the retirement notice now printed with it, the AAN Board of Directors retired the guideline on September 16, 2015, "due to serious safety concerns with a preventative treatment, butterbur, recommended by this guideline." The notice states that the recommendations and conclusions of retired guidelines are considered no longer valid and no longer supported by the AAN, and remain available for reference only. The Level C grade for CoQ10 is therefore a historical grading, not a current AAN position.

Back to Table of Contents

CoQ10, Riboflavin and Magnesium: the Related Trials

CoQ10, riboflavin and magnesium are often discussed together as a "mitochondrial" group of migraine supplements. Each has its own small placebo-controlled trials; one trial has tested a fixed combination of all three.

The riboflavin and magnesium trials

• Schoenen et al. 1998 (Neurology) — riboflavin 400 mg or placebo in 55 patients for 3 months. Riboflavin was superior for attack frequency (p = 0.005) and headache days (p = 0.012); 59% of the riboflavin group and 15% of the placebo group improved by at least 50% in headache days (number needed to treat 2.3). Three minor adverse events occurred: diarrhea and polyuria with riboflavin, abdominal cramps with placebo.
• Peikert et al. 1996 (Cephalalgia) — 81 adults with a mean of 3.6 attacks a month received 600 mg (24 mmol) magnesium as trimagnesium dicitrate daily or placebo for 12 weeks. In weeks 9-12, attack frequency fell by 41.6% with magnesium and 15.8% with placebo (p < 0.05). Diarrhea occurred in 18.6% and gastric irritation in 4.7%.

The one combination trial

In a randomized, double-blind, placebo-controlled trial (Gaul et al. 2015, Journal of Headache and Pain), 130 adults with at least three migraine attacks a month received a fixed-combination supplement of magnesium, riboflavin and CoQ10 or placebo for 3 months. Migraine days a month fell from 6.2 to 4.4 with the supplement and from 6.2 to 5.2 with placebo — a difference that was not statistically significant (p = 0.23), so the trial missed this outcome. Migraine pain intensity (p = 0.03) and the HIT-6 burden-of-disease score (down 4.8 points from 61.9 to 57.1, vs 2 points with placebo; p = 0.01) improved significantly more with the supplement. The trial tested a proprietary product, and it does not show whether the combination works better than any one of its parts.

No trial cited on this page tests whether combining the three nutrients produces a larger effect than any single one.

Back to Table of Contents

Doses Used in the Trials

The doses below are what the cited studies used. They are reported as study details, not as a regimen; questions about supplements and migraine treatment belong with a clinician.

Adults

• Sandor 2005: CoQ10 100 mg three times daily (300 mg/day), outcomes in the third month
• Dahri 2019: CoQ10 400 mg/day for three months, added to preventive medication
• Shoeibi 2017: CoQ10 100 mg daily, added to current preventive drugs (open-label)
• Gaul 2015: a fixed combination of magnesium, riboflavin and CoQ10 for 3 months
• Schoenen 1998: riboflavin 400 mg for 3 months
• Peikert 1996: magnesium 600 mg (24 mmol) as trimagnesium dicitrate daily for 12 weeks

Children and adolescents

• Hershey 2007: 1 to 3 mg/kg per day in patients with low CoQ10, as part of a multidisciplinary plan (uncontrolled)
• Slater 2011: CoQ10 100 mg/day added to standard treatment for 224 days; no difference from placebo at the end

Migraine subtypes

None of the cited trials reports separate results for menstrual migraine, migraine with aura or chronic migraine, so there is no trial evidence on this page for CoQ10 in those groups specifically.

Back to Table of Contents

Combinations With Conventional Migraine Preventives

• As an add-on in trials — in Dahri 2019 all patients were also on preventive medication, in Shoeibi 2017 CoQ10 was added to current preventive drugs, and in Slater 2011 it was added to standard treatment. These trials report headache outcomes, not drug-interaction measurements.
• Specific migraine drugs — the cited studies do not report formal interaction studies between CoQ10 and triptans, gepants, CGRP antibodies, topiramate, beta-blockers, tricyclic antidepressants, valproate, verapamil, botulinum toxin or hormonal therapies. Absence of reported interactions in these small trials is not the same as evidence of no interaction.
• Warfarin — see Cautions below; this is the interaction with the most published data.

Back to Table of Contents

Common Questions

Q: How long did the trials run?
Sandor 2005 compared outcomes in the third treatment month, and Dahri 2019 and Gaul 2015 ran for three months. The pediatric Slater trial ran for 224 days.

Q: Why was CoQ10 given three times a day in the Sandor trial?
The trial used 100 mg three times daily; its abstract does not explain the choice. Absorption of CoQ10 differs widely between products and formulations, as covered on the CoQ10 overview.

Q: Was CoQ10 tested alongside migraine medication?
Yes, in several trials (Dahri 2019, Shoeibi 2017, Slater 2011) it was added to existing preventive treatment. Those trials did not measure drug interactions.

Q: Is the evidence for riboflavin and magnesium the same as for CoQ10?
Each has its own small trials (Schoenen 1998 for riboflavin, Peikert 1996 for magnesium). The single trial of a fixed combination of the three (Gaul 2015) did not significantly reduce migraine days compared with placebo, though pain intensity and disease burden improved.

Q: Does riboflavin change urine colour?
High doses of riboflavin are known to turn urine bright yellow, because the excess vitamin is excreted in the urine. This comes from the riboflavin, not from CoQ10.

Q: Does CoQ10 treat an attack that has already started?
CoQ10 has been studied only as a preventive, taken daily over weeks to months. None of the cited trials tested it as a treatment for an attack in progress.

Q: What does the research show in children?
The uncontrolled Hershey 2007 series reported improvement in children with low CoQ10, but the randomized, placebo-controlled Slater 2011 trial found no difference between CoQ10 and placebo at day 224; children in both groups improved with standard treatment.

Q: Has CoQ10 been studied in pregnancy?
Not for migraine. In a randomized, placebo-controlled trial in 235 women at increased risk of pre-eclampsia (Teran et al. 2009), CoQ10 200 mg/day from 20 weeks to delivery was associated with less pre-eclampsia (14.4% vs 25.6%). Published safety data in pregnancy are limited to small trials of this kind. Decisions about medicines and supplements in pregnancy belong with a clinician.

Back to Table of Contents

Cautions

• Warfarin — A 1994 report described a reduced effect of warfarin caused by CoQ10 (Spigset 1994), and a few such case reports exist. In a randomized, double-blind, placebo-controlled crossover trial in 24 outpatients on stable long-term warfarin (Engelsen et al. 2003), CoQ10 100 mg/day for four weeks did not change the INR or the warfarin dose.
• Butterbur — the AAN retired its 2012 guideline because of "serious safety concerns" with butterbur, which the guideline had graded Level A.
• Magnesium — in the Peikert trial of 600 mg magnesium daily, diarrhea occurred in 18.6% of patients and gastric irritation in 4.7%.
• CoQ10 tolerability — CoQ10 was described as well tolerated in the Sandor trial, and no side effects of CoQ10 were observed in the Shoeibi trial.
• Preventive, not acute — CoQ10 has been studied only for prevention; the trials kept patients on their usual treatments.
• Warning signs — medical guidance commonly lists a new headache after age 50, a sudden "thunderclap" headache, headache with new neurological symptoms (weakness, loss of vision, confusion) or with fever and other systemic symptoms, and headaches that are steadily worsening, as reasons for prompt medical evaluation rather than self-treatment.

Back to Table of Contents

Key Research Papers

1. Sándor PS, Di Clemente L, Coppola G, et al. (2005). Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology 64(4):713-715. — PubMed PMID: 15728298
2. Hershey AD, Powers SW, Vockell AL, et al. (2007). Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. Headache 47(1):73-80. — PubMed PMID: 17355497
3. Parohan M, Sarraf P, Javanbakht MH, et al. (2020). Effect of coenzyme Q10 supplementation on clinical features of migraine: a systematic review and dose-response meta-analysis of randomized controlled trials. Nutritional Neuroscience 23(11):868-875. — PubMed PMID: 30727862
4. Sazali S, Badrin S, Norhayati MN, Idris NS (2021). Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine — a meta-analysis. BMJ Open 11(1):e039358. — PubMed PMID: 33402403
5. Holland S, Silberstein SD, Freitag F, et al. (American Academy of Neurology / American Headache Society, 2012). Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults. Neurology 78(17):1346-1353. Retired by the AAN on September 16, 2015 (retirement notice printed with the PMC copy, PMC3335449). — PubMed PMID: 22529203
6. Schoenen J, Jacquy J, Lenaerts M (1998). Effectiveness of high-dose riboflavin in migraine prophylaxis: a randomized controlled trial. Neurology 50(2):466-470. — PubMed PMID: 9484373
7. Peikert A, Wilimzig C, Köhne-Volland R (1996). Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 16(4):257-263. — PubMed PMID: 8792038
8. Slater SK, Nelson TD, Kabbouche MA, et al. (2011). A randomized, double-blinded, placebo-controlled, crossover, add-on study of CoEnzyme Q10 in the prevention of pediatric and adolescent migraine. Cephalalgia 31(8):897-905. — PubMed PMID: 21586650
9. Welch KM, Ramadan NM (1995). Mitochondria, magnesium and migraine. Journal of the Neurological Sciences 134(1-2):9-14. — PubMed PMID: 8747836
10. Dahri M, Tarighat-Esfanjani A, Asghari-Jafarabadi M, Hashemilar M (2019). Oral coenzyme Q10 supplementation in patients with migraine: effects on clinical features and inflammatory markers. Nutritional Neuroscience 22(9):607-615. — PubMed PMID: 29298622
11. Shoeibi A, Olfati N, Soltani Sabi M, et al. (2017). Effectiveness of coenzyme Q10 in prophylactic treatment of migraine headache: an open-label, add-on, controlled trial. Acta Neurologica Belgica 117(1):103-109. — PubMed PMID: 27670440
12. Charles A, Brennan K (2009). Cortical spreading depression — new insights and persistent questions. Cephalalgia 29(10):1115-1124. — PubMed PMID: 19735537
13. Zeng Z, Li Y, Lu S, Huang W, Di W (2019). Efficacy of CoQ10 as supplementation for migraine: a meta-analysis. Acta Neurologica Scandinavica 139(3):284-293. — PubMed PMID: 30428123
14. Okoli GN, Rabbani R, Kashani HH, et al. (2019). Vitamins and minerals for migraine prophylaxis: a systematic review and meta-analysis. Canadian Journal of Neurological Sciences 46(2):224-233. — PubMed PMID: 30764890
15. Gaul C, Diener HC, Danesch U (2015). Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial. Journal of Headache and Pain 16:516. — PubMed PMID: 25916335
16. Spigset O (1994). Reduced effect of warfarin caused by ubidecarenone. Lancet 344(8933):1372-1373. — PubMed PMID: 7968059
17. Engelsen J, Nielsen JD, Hansen KF (2003). Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled cross-over trial. (article in Danish, English abstract) Ugeskrift for Laeger 165(18):1868-1871. — PubMed PMID: 12772396
18. Teran E, Hernandez I, Nieto B, et al. (2009). Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia. International Journal of Gynaecology and Obstetrics 105(1):43-45. — PubMed PMID: 19154996

PubMed Topic Searches

1. PubMed: coenzyme Q10 migraine prevention
2. PubMed: riboflavin, coenzyme Q10 and magnesium in migraine
3. PubMed: cortical spreading depression mitochondria
4. PubMed: migraine mitochondria 31P-MRS
5. PubMed: pediatric migraine nutraceuticals
6. PubMed: AAN/AHS nutraceutical guideline

Back to Table of Contents

Connections

• Free Radicals & Your Antioxidant Network — interactive animation
• CoQ10 Overview
• CoQ10 Benefits Hub
• CoQ10 for Heart Failure
• CoQ10 for Statin Myopathy
• CoQ10 for Fertility
• Headache & Migraine
• Vitamin B2 (Riboflavin)
• Magnesium
• Vitamin D
• Alpha Lipoic Acid
• All Antioxidants
• L-Carnitine
• Creatine
• Oxidative Stress
• Sleep Hygiene
• Stress Management
• History

Back to Table of Contents

Featured Videos