Migraine headaches are often debilitating, underdiagnosed and, unfortunately, quite common. Estimates put the prevalence of migraines at roughly 12 percent in the U.S. and slightly higher in Canada, with women affected three times more frequently than men.(1,2) Here, I’ll be reviewing both effective and safe therapies for migraine, and to also mention two key principles of naturopathic medicine applicable to individualized and public health approaches to migraine treatment. The first is prevention; currently only 12 percent of individuals with migraine (migraineurs) in the U.S. use any form of preventative therapy, while 98 percent use some form of acute treatment.(3) Given that most natural therapies are effective for migraine prophylaxis (rather than acute treatment) and without adverse effects, they may be the most appropriate choice for many migraineurs.
The second principle I’d like to mention is identifying and treating the cause, rather than only treating symptoms, which seems particularly applicable to migraines. The relevance becomes clearer after examining what migraine, or at least a diagnosis of migraine means. Because migraine does not have one specific etiology, such as an infection, tumor, etc. the pathophysiology responsible for causing symptoms is not necessarily the same between two people, nor are the symptoms necessarily the same. In fact, there is not one specific symptom unique to migraine (i.e., not found in other types of headaches), but rather the diagnosis of migraine is an amalgam of symptoms defined by convention. Another way of looking at this is that successful treatment is more likely if we attempt to determine the cause of the headaches on an individual basis, rather than prescribe treatment based solely upon a diagnosis of migraine.
Underlying Dysfunctions and Therapies
Most migraineurs are thought to have a trigger for their headaches, though these triggers are quite diverse (such as stress, lack of sleep, hormonal changes, foods, etc.) and sometimes difficult to identify.(4) Most migraineurs also seem to share some degree of cortical hyperexcitability (i.e. oversensitive nerve cells in the brain), which after being exposed to a trigger, initiate a series of neurological and vascular changes responsible for the symptoms of migraine.(5) What determines that heightened sensitivity is not well understood, but a number of metabolic and nutritional factors seem to be play an important role. Below are some examples of contributing factors, as well as therapies that may be most appropriate for each.
Histamine, Butterbur and Foods
Some migraine are likely to have an abnormal release of histamine in response to various triggers. One finding, which has helped to confirm this notion, is that other conditions with excessive histamine releases occur more commonly with migraine. For example, in people with allergic rhinitis, the incidence of migraine was found to be 14 times greater when compared to a control population, and increases have also been documented for asthma and atopic dermatitis.(6,7,8) This subset of migraineurs is thus most likely to respond to treatments limiting histamine release, such as IgE (Immunoglobulin E)-based food allergy testing, as well as the herb butterbur. For example, one study found that approximately 40 percent of children with migraines had IgE antibodies when tested, and their headaches resolved with treatments targeting histamine release.(9) Studies in adults have also shown relief after identifying food allergies, followed by avoidance of those foods.(10)
The herb butterbur was first used to treat allergic rhinitis because it prevents the release of histamine from mast cells (this release is triggered by IgE antibodies), and was found to be equally effective when compared to standard allergy medications in controlled trials.(11) When used for migraine, approximately 45 percent of children and adults experience at least a 50 percent reduction in headache frequency (a standard measure for efficacy).(12,13) Interestingly, this is approximately the same percentage of children with migraines that had elevated IgE.
Mitochondria, CoQ10, Magnesium and Riboflavin
Another contributing factor to migraines in some individuals appears to be dysfunction in the organelles responsible for energy (ATP) production, the mitochondria. Long suspected to have a role in migraine pathophysiology, recent analysis has helped confirm a role for mitochondria using a technique called phosphorus magnetic resonance spectroscopy analyses (PMRS). This non-invasive test monitors ATP production and brain energy metabolism. Researchers documented an “unstable metabolic state of the brain and a decreased ability to cope with further energy demand” among those with migraines.(14) Further confirmation has come from genomic analysis of mitochondrial DNA in migraineurs, which found two polymorphisms (genetic variants) which conferred a 3.6- and a 1-fold risk for migraine, strongly suggesting mitochondrial involvement in at least some individuals.(15)
This may help to explain the benefits of CoQ10 and riboflavin, two nutrients that have been shown to reduce headache frequency, most likely by improving mitochondrial function. For example, in a recent study of children and adolescents, roughly three-quarters were found to have suboptimal levels of CoQ10.(16) Treatment with CoQ10 was found to reduce migraines in this study, as well as in a randomized and doubleblinded trial.(17)
Riboflavin has also been shown to reduce migraine frequency in half (in both children and adults) in 60-70 percent of migraineurs (vs. 15 percent placebo) in controlled trials.(18,19) I have found two additional studies with riboflavin to be quite striking. The first compared riboflavin to a beta-blocker, a medication also used prophylactically for migraine. Researchers found that both treatments were equally effective for reducing symptoms. However, they monitored a marker of nerve cell (cortical) activity in the brain, and found that the two treatments did not have the same effect on this marker of cortical activity – thus despite equal clinical efficacy, they appear to have worked via different mechanisms. This strongly suggests not only that one treatment may work if the other does not (or must be discontinued due to adverse effects), but that if used together they may have additive effects.(20)
The second study evaluated the use of riboflavin among patients with different haplogroups, a term which indicates some commonalities in mitochondrial DNA. They found that although the overall success rate was approximately 60 percent (similar to previous trials), it did differ by haplogroup (45 percent vs. 77 percent).(21) This indicates both a mitochondrial role in migraine (in some individuals), as well as the possibility of identifying by genetic analysis those more likely to respond to specific therapies.
Finally, magnesium – a common mineral deficiency(22) – is very helpful for most people with migraine.(23) This is likely due to its support for mitochondrial function as well as muscle relaxation.
Other treatments that have shown to be effective for migraine prophylaxis include vitamin B6, folic acid, B12, melatonin, lipoic acid, feverfew, omega-3 fatty acids and possibly vitamin D supplementation. Additionally, dietary interventions that identify food triggers – either based upon IgE or IgG antibody testing, elimination diets or via restriction of biogenic amines – have a role in preventing migraines on an individual basis. The two contributing factors I have highlighted (mitochondrial dysfunction and histamine dysregulation) are examples of how two individuals who meet the same broad criteria for having a migraine might have very different underlying etiologies, and respond differently to treatment. My hope is that we continue to push in this direction, to identify the biochemically uniqueness of each individual and treat them appropriately, rather than just treating disease. Or in the case of migraine, just treating criteria for the diagnosis of disease.
To emphasise this a bit more, some migraineurs have genetic polymorphisms for the gene MTHFR, which interferes with folic acid metabolism. Not only does this make them more likely to have migraines, it also puts them at greater risk for peripheral and central cardiovascular disease.(24,25,26) Variants in this gene also appear to predict the actual symptoms that migraineurs have, again suggesting that migraine symptoms are not random, but reflective of underlying pathology.(27) Treatments targeted at improving folic acid metabolism thus not only reduce migraine, but they also may prevent stroke due to the shared pathology behind both conditions, providing a clear example of how treating underlying dysfunction has so much broader benefit than treating symptoms alone.(28,29)
1. Cooke LJ, Becker WJ. Migraine prevalence, treatment and impact: the Canadian women and migraine study. Can J Neurol Sci. 2010 Sep;37(5):580-7.
2. Lipton RB, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007 Jan 30;68(5):343-9.
3. Diamond S, Bigal ME et al. Patterns of diagnosis and acute and preventive treatment for migraine in the United States: results from the American Migraine Prevalence and Prevention study. Headache. 2007 Mar;47(3):355-63.
4. Levy D, et al. A critical view on the role of migraine triggers in the genesis of migraine pain. Headache. 2009 Jun;49(6):953-7.
5. Goadsby PJ. The vascular theory of migraine–a great story wrecked by the facts. Brain. 2009 Jan;132(Pt 1):6-7.
6. Ku M, et al. Prevalence of migraine headaches in patients with allergic rhinitis. Ann Allergy Asthma Immunol. 2006 Aug;97(2):226-30.
7. Aamodt AH, et al., Is headache related to asthma, hay fever, and chronic bronchitis? The Head-HUNT Study. Headache. 2007 Feb;47(2):204-12.
8. Mortimer MJ, et al. The prevalence of headache and migraine in atopic children: an epidemiological study in general practice. Headache. 1993 Sep;33(8):427-31.
9. Wendorff J, et al. [Allergy effect on migraine course in older children and adolescents]. Neurol Neurochir Pol. 1999;33 Suppl 5:55-65.
10. Mansfield LE, et al. Food allergy and adult migraine: double-blind and mediator confirmation of an allergic etiology. Ann Allergy. 1985 Aug;55(2):126-9.
11. Schapowal A; Study Group. Treating intermittent allergic rhinitis: a prospective, randomized, placebo and antihistamine-controlled study of Butterbur extract Ze 339. Phytother Res. 2005 Jun;19(6):530-7.
12. Diener HC, et al. The first placebo-controlled trial of a special butterbur root extract for the prevention of migraine: reanalysis of efficacy criteria. Eur Neurol. 2004;51(2):89-97. Epub 2004 Jan 28.
13. Agosti R, et al. Effectiveness of Petasites hybridus preparations in the prophylaxis of migraine: a systematic review. Phytomedicine. 2006 Nov;13(9-10):743-6. Epub 2006 Sep 20.
14. Sparaco M, et al. Mitochondrial dysfunction and migraine: evidence and hypotheses. Cephalalgia. 2006 Apr;26(4):361-72.
15. Zaki EA, et al. Two common mitochondrial DNA polymorphisms are highly associated with migraine headache and cyclic vomiting syndrome. Cephalalgia. 2009 Jul;29(7):719-28.
16. Hershey AD, et al. Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. Headache. 2007 Jan;47(1):73-80.
17. Sándor PS, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology. 2005 Feb 22;64(4):713-5.
18. Schoenen J, et al. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology. 1998 Feb;50(2):466-70.
19. Condò M, et al. Riboflavin prophylaxis in pediatric and adolescent migraine. J Headache Pain. 2009 Oct;10(5):361-5.
20. Sándor PS, et al. Prophylactic treatment of migraine with beta-blockers and riboflavin: differential effects on the intensity dependence of auditory evoked cortical potentials. Headache. 2000 Jan;40(1):30-5.
21. Di Lorenzo C, et al. Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs. Neurology. 2009 May 5;72(18):1588-94.
22. Ramadan NM, Halvorson H, Vande-Linde A, et al. Low brain magnesiumin migraine. Headache. 1989;29:590-593
23. Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine – a double-blind placebo-controlled study. Cephalalgia. 1996;16:436-440
24. Khandanpour N, et al. Peripheral arterial disease and methylenetetrahydrofolate reductase (MTHFR) C677T mutations: A case-control study and meta-analysis. J Vasc Surg. 2009 Mar;49(3):711-8.
25. Durga J, et al. Homocysteine and carotid intima-media thickness: a critical appraisal of the evidence. Atherosclerosis. 2004 Sep;176(1):1-19.
26. Schürks M, et al. MTHFR 677C>T and ACE D/I polymorphisms in migraine: a systematic review and meta-analysis. Headache. 2010 Apr;50(4):588-99.
27. Liu A, et al. Analysis of the MTHFR C677T variant with migraine phenotypes. BMC Res Notes. 2010 Jul 28;3:213.
28. Lea R, et al. The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. Pharmacogenet Genomics. 2009 Jun;19(6):422-8.
29. Di Rosa G, et al. Efficacy of folic acid in children with migraine, hyperhomocysteinemia and MTHFR polymorphisms. Headache. 2007 Oct;47(9):1342-4.
Dr. Joseph Pizzorno, ND Chair, Scientific Advisory Board; Bioclinic Naturals POB 25801
Seattle, WA 98165-1301
p: (206) 368-5403
f: (206) 368-8570