Treating the Underlying Causes of Chronic Migraine

Flat lay of healthy fat sources, salmon, various nuts, and avocado that make up the ketogenic diet, one of the functional medicine treatments for chronic migraines.
Read Time 5 Minutes

Headache disorders have recently been ranked worldwide as the second leading cause of years lived with a disability,1 with migraine headache recognized globally as one of the highest contributors to disability for those under 50 years of age.2 Chronic migraine, specifically, has been noted as the most common type of daily headache seen by headache specialists. Chronic migraine often occurs as a typical progression from episodic migraine (less than 15 headache days per month) and displays its own unique physiology.3Approximately 2% of the global population experience chronic migraine, with a higher frequency noted for women. About 3% of those who have episodic migraine progress to chronic each year.3
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Clinical, neurophysiologic, and functional imaging studies have suggested that alterations can occur in the brains of patients with chronic migraine compared to those with episodic migraine.3 Also, patients with chronic migraine experience higher rates of comorbidities, including impaired sleep, anxiety and depression, and gastrointestinal disorders,3 all of which can greatly impact quality of life.

One challenge in the treatment and prevention of migraine is that the underlying etiology is often not clear. A range of migraine triggers has been noted; however, if the exact cause for an individual is not known, this may create difficulty in selecting an appropriate treatment intervention.


Migraine is a complex issue related to the interaction between genetic, environmental, and lifestyle factors. And this interaction may manifest differently for each individual patient. While the exact pathophysiology of migraine is unclear, some etiologies have been suggested, such as:

  • An overall pro-inflammatory and oxidative state.2
  • Mitochondrial dysfunction.4,5
  • Common migraine triggers such as stress, environmental allergens, and food allergens or sensitivities.6

Migraine has been associated with inflammatory diseases,7 and modifiable risk factors have been identified, including obesity, comorbid pain conditions, and sleep problems.8 Causes of migraine may vary for each individual patient, creating a challenge for treatment considerations and prevention.

In the following video, IFM educator Lisa Portera-Perry, DC, discusses possible chronic migraine etiologies, such as mitochondrial dysfunction, and specific nutrients that could be used as effective treatment or prevention.


(Video Time: 1 minute). Dr. Portera-Perry is an adjunct clinical faculty member of Bastyr University’s teaching clinic in San Diego, CA, as an integrative Doctor of Chiropractic. She is also a member of Bastyr’s adjunct teaching faculty, teaching courses in integrative nutrition and physical medicine.

Mitochondrial Dysfunction, Triggers, and Oxidative Stress

Some studies have reported dysfunction of mitochondrial metabolism in migraine patients,4,5,9 suggesting that mitochondria may play an important role in migraine development and progression. In addition, one survey-based study found that the prevalence of headache, including migraine, was higher in patients who had a mitochondrial disease as compared to the general population.10 A recent study further suggests that the epigenetic modifications of mitochondria in the scope of migraine is an area needing investigation.4

Oxidative stress is a factor in the development of many diseases, including the development of migraine.4,5 A recent review was conducted to determine if and to what capacity common migraine triggers such as stress, dietary nitrates, and dehydration generate oxidative stress in the brain.11 The review noted that some of these triggers are not only capable of generating oxidative stress, but, depending on the trigger, the mechanisms that cause that stress may include mitochondrial dysfunction.11

GI Disorders

Various functional gastrointestinal (GI) disorders have been shown to be frequently comorbid with migraine.12-15 A 2022 observational study (n=781,115 patients from the national South Korean health and medical database) reported that the prevalence of migraine was almost 3.5 times higher in patients with one or more GI diseases (adjusted OR=3.46, CI: 3.30-3.63), and prevalence increased with the number of GI conditions.16 A comprehensive review of health literature reported on specific GI conditions linked to migraine.17 For example, an included 2014 meta-analysis of five case-control studies found that the rate of H. pylori infection was 45% in patients with migraine versus a 33% infection rate in control groups.17,18 For irritable bowel syndrome (IBS), in population studies, 6-32% of IBS patients reported migraine-type headaches versus 2.2-18% in the control group.17 For celiac disease (CD), there was a reported 21% prevalence of migraine in the CD group versus 6% in the control group.17 The review suggested that further investigation is needed to clearly define the pathways of GI disorders and migraine and to evaluate the impact of screening and therapeutic measures that may lead to improved outcomes and a better quality of life for the patient.17

How GI disorders may impact migraine progression is unclear; however, inflammation in the GI tract and intestinal permeability have been suggested as influences.15 According to a recent review of dietary interventions for migraine, the gut microbiome is suspected to play a role in the progression of migraine via the gut-brain axis, even though this hypothesized relationship remains unsubstantiated.19,20

Treatment Considerations and Prevention

Clinicians should consider nutritional interventions to address chronic migraine and to help improve a patient’s quality of life. In particular, nutrition interventions with the inclusion of specific nutrients in the diet can help support mitochondrial function. The following are examples:

  • The ketogenic diet is a therapeutic intervention that targets cerebral metabolism and has suggested relevance in migraine prevention, according to some observational case studies.21,22 Ketogenic diets have been proposed to promote neuroprotection, improve mitochondrial function, compensate for serotoninergic dysfunction, decrease calcitonin gene-related peptide (CGRP) levels, and suppress neuroinflammation.22
  • Nutrients such as riboflavin, coenzyme Q10, and magnesium may also be beneficial in migraine prevention.23 One study suggested that a supplement combining coenzyme Q10, magnesium, and feverfew (Tanacetum parthenium ), a medicinal plant,24 may be beneficial and safe for migraine prophylaxis.25 Additionally, folate, which is involved in DNA methylation, has been shown to be beneficial in migraine; research suggests that defining a diet that can target DNA methylation—for example, a folate-rich diet—could potentially provide a future direction for migraine-related dietary studies.22

Primary goals of migraine treatments are to relieve pain, restore function, reduce frequency, and prevent progression from episodic to chronic migraine.26 From a functional medicine perspective, supporting mitochondrial function, avoiding potential triggers, and engaging patients in their treatments are strategies that may improve long-term outcomes. Functional medicine is a model that can assess an individual patient’s genetic, biochemical, and lifestyle factors to help create a personalized treatment plan for their chronic migraine diagnosis.

Learn More About Mitochondrial Function

Decreasing Migraine Frequency With Nutrition

Food Reactions, Eczema, and Migraines

Ketogenic Diet in Neurodegenerative Diseases

Mitochondrial Dysfunction and Chronic Pain Patients


  1. GBD 2016 Headache Collaborators. Global, regional and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):954-976. doi:10.1016/S1474-4422(18)30322-3
  2. Razeghi Jahromi S, Ghorbank Z, Martelletti P, Lampl C, Togha M. Association of diet and headache. J Headache Pain. 2019;20(1):106. doi:10.1186/s10194-019-1057-1
  3. Aurora SK, Brin MF. Chronic migraine: an update on physiology, imaging, and the mechanism of action of two available pharmacologic therapies. Headache. 2017;57(1):109-125. doi:10.1111/head.12999
  4. Fila M, Pawlowska E, Blasiak J. Mitochondria in migraine pathophysiology – does epigenetics play a role? Arch Med Sci. 2019;15(4):944-956. doi:10.5114/aoms.2019.86061
  5. Khan J, Asoom LIA, Sunni AA, et al. Genetics, pathophysiology, diagnosis, treatment, management, and prevention of migraine. Biomed Pharmacother. 2021;139:111557. doi:1016/j.biopha.2021.111557
  6. Kelman L. The triggers or precipitants of the acute migraine attack. Cephalalgia. 2007;27(5):394-402. doi:10.1111/j.1468-2982.2007.01303.x
  7. Min C, Lim H, Lim JS, Sim S, Choi HG. Increased risk of migraine in patients with psoriasis: a longitudinal follow up study using a national sample cohort. Medicine (Baltimore). 2019;98(17):e15370. doi:10.1097/MD.0000000000015370
  8. Scher AI, Midgette LA, Lipton RB. Risk factors for headache chronification. Headache. 2008;48(1):16-25. doi:10.1111/j.1526-4610.2007.00970.x
  9. Sarchielli P, Tarducci R, Presciutti O, et al. Functional 1H-MRS findings in migraine patients with and without aura assessed interictally. Neuroimage. 2005;24(4):1025-1031. doi:10.1016/j.neuroimage.2004.11.005
  10.  Kraya T, Deschauer M, Joshi PR, Zierz S, Gaul C. Prevalence of headache in patients with mitochondrial disease: a cross-sectional study. Headache. 2018;58(1):45-52. doi:10.1111/head.13219
  11.  Borkum JM. Migraine triggers and oxidative stress: a narrative review and synthesis. Headache. 2016;56(1):12-35. doi:10.1111/head.12725
  12.  Talafi Noghani M, Namdar H. Migraine associated with gastrointestinal disorders: a pathophysiological explanation. Med Hypotheses. 2019;125:90-93. doi:10.1016/j.mehy.2019.02.041
  13.  Martami F, Ghorbani Z, Abolhasani M, et al. Comorbidity of gastrointestinal disorders, migraine, and tension-type headache: a cross sectional study in Iran. Neurol Sci. 2018;39(1):63-70. doi:10.1007/s10072-017-3141-0
  14.  Lankarani KB, Akbari M, Tabrizi R. Association of gastrointestinal functional disorders and migraine headache: a population base study. Middle East J Dig Dis. 2017;9(3):139-145. doi:10.15171/mejdd.2017.64
  15.  van Hemert S, Breedveld AC, Rovers JMP, et al. Migraine associated with gastrointestinal disorders: review of literature and clinical implications. Front Neurol. 2014;5:241. doi:10.3389/fneur.2014.00241
  16.  Kim J, Lee S, Rhew K. Association between gastrointestinal diseases and migraine. Int J Environ Res Public Health. 2022;19(7):4018. doi:3390/ijerph19074018
  17.  Cámara-Lemarroy CR, Rodriguez-Gutierrez R, Monreal-Robles R, Marfil-Rivera A. Gastrointestinal disorders associated with migraine: a comprehensive review. World J Gastroenterol. 2016;22(36):8149-8160. doi:10.3748/wjg.v22.i36.8149
  18.  Su J, Zhou XY, Zhang GX. Association between Helicobacter pylori infection and migraine: a meta-analysis. World J Gastroenterol. 2014;20(40):14965-14972. doi:3748/wjg.v20.i40.14965
  19.  Slavin M, Li HA, Frankenfeld C, Cheskin LJ. What is needed for evidence-based dietary recommendations for migraine: a call to action for nutrition and microbiome research. Headache. 2019;59(9):1566-1581. doi:10.1111/head.13658
  20.  Arzani M, Jahromi SR, Ghorbani Z, et al. Gut-brain axis and migraine headache: a comprehensive review. J Headache Pain. 2020;21(1):15. doi:10.1186/s10194-020-1078-9
  21.  Gross EC, Klement RJ, Schoenen J, D’Agostino DP, Fischer D. Potential protective mechanisms of ketone bodies in migraine prevention. Nutrients. 2019;11(4):E811. doi:10.3390/nu11040811
  22.  Gazerani P. Migraine and diet. Nutrients. 2020;12(6):1658. doi:10.3390/nu12061658
  23.  Silberstein SD. Preventive migraine treatment. Continuum. 2015;21(4 Headache):973-989. doi:10.1212/CON.0000000000000199
  24.  Pareek A, Suthar M, Rathore GS, Bansal V. Feverfew (Tanacetum parthenium L.): a systematic review. Pharmacogn Rev. 2011;5(9):103-110. doi:10.4103/0973-7847.79105
  25.  Guilbot A, Bangratz M, Abdellah SA, Lucas C. A combination of coenzyme Q10, feverfew and magnesium for migraine prophylaxis: a prospective observational study. BMC Complement Altern Med. 2017;17(1):433. doi:10.1186/s12906-017-1933-7
  26.  Lipton RB, Silberstein SD. Episodic and chronic migraine headache: breaking down barriers to optimal treatment and prevention. Headache. 2015;55(Suppl 2):103-122. doi:10.1111/head.12505_2


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