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 headaches per month) and displays its own unique physiology.3
Approximately 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
Clinical, neurophysiologic, and functional imaging studies have suggested that alterations can occur in the brains of patients with chronic migraine compared to episodic migraine.3 Also compared to episodic migraine, patients with chronic migraine experience higher rates of co-morbidities, 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 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.
The issue is, why are they getting the migraines? What is causing them to be chronic?
-Robert Rountree, MD, IFM educator
In the following video, Robert Rountree, MD, discusses possible chronic migraine etiologies, such as mitochondrial dysfunction, and specific nutrients that could be used as effective treatment or prevention.
Migraine is a complex disease potentially determined by 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 state2
- Mitochondrial dysfunction4
- Common migraine triggers such as stress, environmental allergens, and food allergens or sensitivities5
Migraine has been associated with inflammatory diseases,6 and modifiable risk factors have been identified, including obesity, co-morbid pain conditions, and sleep problems.7 Causes of migraine vary for each individual patient, creating a challenge for treatment considerations and prevention.
Mitochondrial Dysfunction, Triggers, and Oxidative Stress
Some studies have reported dysfunction of mitochondrial metabolism in migraine patients,4,8 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.9 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 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. 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.10
Various functional gastrointestinal (GI) disorders have been shown to have a frequent comorbidity with migraine.11-14 A recent comprehensive review investigated GI disorders associated with migraine and found an increased frequency of GI disorders in patients with migraine compared with the general population.15 Specifically, in H. pylori investigations that were reviewed, there was a 45% infection rate in patients with migraine versus a 33% infection rate in control groups.15 For irritable bowel syndrome (IBS) investigations, 6–32% of IBS patients reported migraine-type headaches versus 2.2–18% in the control group.15 For celiac disease (CD) investigations, there was a reported 21% prevalence of migraine in the CD group versus 6% in the control group.15 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.15
How GI disorders may impact migraine progression is unclear; however, inflammation in the GI tract and intestinal permeability have been suggested as influences.14 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.16
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 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 observational case studies.17
- Nutrients such as riboflavin, coenzyme Q10, and magnesium may also be beneficial in the preventative treatment of migraine.18 One study suggested that a supplement that combined coenzyme Q10, magnesium, and feverfew (Tanacetum parthenium ), a medicinal plant,19 may be beneficial and safe for migraine prophylaxis.20
Primary goals of migraine treatments are to relieve pain, restore function, reduce frequency, and prevent progression from episodic to chronic migraine.21 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. For more information on migraine, please read the following IFM-authored articles.
- 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
- 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
- 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
- Fila M, Paw?owska 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
- 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
- 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
- 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
- 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
- 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
- Borkum JM. Migraine triggers and oxidative stress: a narrative review and synthesis. Headache. 2016;56(1):12-35. doi:10.1111/head.12725
- Talafi Noghani M, Namdar H. Migraine associated with gastrointestinal disorders: a pathophysiological explanation. Medical Hypotheses. 2019;125:90-93. doi:10.1016/j.mehy.2019.02.041
- 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
- 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
- van Hemert S, Breedveld AC, Rovers JM, et al. Migraine associated with gastrointestinal disorders: review of literature and clinical implications. Front Neurol. 2014;5:241. doi:10.3389/fneur.2014.00241
- 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
- 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
- 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
- Silberstein SD. Preventive migraine treatment. Continuum. 2015;21(4 Headache):973-989. doi:10.1212/CON.0000000000000199
- 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
- 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
- Lipton RB, Silberstein SD. Episodic and chronic migraine headache: breaking down barriers to optimal treatment and prevention. Headache. 2015;55(S2):103-122. doi:10.1111/head.12505_2
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