Nourishing a migraine brain
One in seven people in the UK suffer migraines, an annual financial burden of over £3.5bn to the economy in respect of the costs of health care and missed work (1).
This article considers some of current thinking relating to genetic differences in sufferers who potentially share common risk factors and proposes that nutritional therapy may be able to support sufferers instead of opting for conventional treatment.
What is a Migraine?
Migraine is a highly debilitating condition, and is more prevalent in women than men by a ratio of 3:1, although prior to puberty, the prevalence is higher in boys than girls (2). Women are more likely to have migraines around their menstrual cycles and headaches seem to happen in response to hormonal changes in men too.
There are many variations of migraine and all types have yet to be determined. Migraines normally manifest themselves as painful headaches lasting from 4 to 72 hours, consisting of three parts. Typically there is a prelude (prodrome), varying from individual to individual often involving symptoms such as nausea, vomiting, diarrhoea, vertigo, anxiety, cravings (3). Next, the migraine itself can last between 48 and 72 hours, usually with severe head pain, and may include an aura, where brain cells become hypersensitive and begin chemical changes in the brain, causing visual effects (4). Thirdly, postdrome follows, where sufferers have extreme exhaustion, possible brain fog or memory block.
What causes Migraine?
Migraine can be caused by many factors, varying from individual to individual, eg, genetics, hormones, age, poor diet, stress, other medical conditions, and environmental factors (5). Triggers such as foods, light, sound, stress, weather changes and sleep disturbance create an abnormal event in an area of the brain where some of the cells are unable to generate sufficient electrical activity, and therefore do not function normally. This leads to a slow-moving wave of abnormal electrical activity in the brain (called cortical spreading depression - which produces the visual and sensory changes that are the common forms of aura), which eventually reaches certain nerve pathways that get stimulated more easily in sufferers. This stimulation causes the pain and inflammation. The inflammation leads to the release of a series of chemicals and a cascade of inflammatory responses (6, 7).
The underlying causes of this spread of inflammation and subsequent pain are not fully understood. Once thought to be due to blood vessels both constricting and dilating in the brain, the thinking has shifted - it is now considered primarily a neurological syndrome having subsequent consequences on blood vessels in the brain (8).
Migraine is akin to chasing a moving target; what works to alleviate the condition for one person may not work for another.
Medications such as NSAID’s, paracetamol, opioids, anti-emetics and preventative medications are typically prescribed for the relief of the pain rather than the underlying cause. The mainstay acute treatment for migraines are a class of drugs called triptans, which act on serotonin receptors and can be highly effective (9), but if the timing of taking the medications does not work alongside the balance of other chemicals present in the brain then medication may be ineffective (10).
The Role of Genetics?
There are interesting theories pointing to migraine sufferers potentially having genetic differences, with a greater predisposition to migraines than non-sufferers including greater hypersensitivity (11,12). These differences may lead to biochemical imbalances in the brain bought on by the factors described above, leading to neurogenic inflammation (13).
Emerging research pinpoints a genetic connection with certain variations in DNA in people that are predisposed to migraine, yet there are a wide number of gene types implicated in migraine (14). One hypothesis by Dr. Angela Stanton in her book “Fighting the Migraine Epidemic” (15), is based upon observational studies and treatment of over 5,000 sufferers. Her work has been peer reviewed.
Stanton proposes that migraine is largely a function of genetics. She hypothesises that the many genetic variants that predispose sufferers are an extreme sensitivity to fluctuations in biochemical balances in the brain (homeostasis) (6). These are principally imbalances in electrolyte mineral density, (sodium, chloride and potassium) (16 p.87). She suggests that sufferers have a genetic requirement to generate more electrical energy than non-sufferers and therefore a greater need for sodium (in the majority of cases) or potassium (17,18) in order to generate the right electrical levels for their individual biochemistry and to achieve and maintain homeostasis.
Magnesium is also considered key, as the required starting engine to generate sufficient energy, key to warding off the a migraine at the early stages. The strongest evidence for magnesium’s effectiveness is in patients who have, or have had, aura with their migraines. It is believed magnesium may prevent the wave of cortical spreading depression. Magnesium may also prevent narrowing of brain blood vessels caused by the neurotransmitter serotonin (19).
Stanton proposes sufferers struggle to achieve homeostasis and that the under supply of correct electrolytes may trigger changes in the brain, leading to migraines. Migraine suffers can be hyper-sensitive to certain sights, sounds and smells amongst other things, which can trigger an attack (20). It is the chain of events that follows the stimulus that depletes the salts needed to generate the right electrical levels.
Carbohydrate Dysfunction?
Sufferers may have a lower tolerance to carbohydrates and a form of blood sugar imbalance, which could be a considerable risk factor (21,22,23). They may crave sweets prior to a migraine (at the prodrome stage) (24 p.132). This could represent a signal of impending energy shortage as the nerve cells cannot access glucose normally, if the required chemicals such as sodium, chloride, calcium, potassium and magnesium are not readily available (25).
This may help to explain why a blood sugar imbalance in sufferers often goes hand in hand with other conditions such as weight problems and insulin resistance even though the precise relationship is still unclear (23).
The presence of other hormones may affect glucose regulation, whether they be fluctuating female cycle hormones, stress related hormones or insulin hormone. Variations in hormones may cause changes in metabolic regulation, causing glucose excess, reducing sodium and creating the biochemical imbalance, which may trigger migraine. This is because insulin receptors will prioritise hormones to process over glucose (25). As an example, certain migraine medications manipulate serotonin. As serotonin also occupies insulin receptors, glucose can build up, potentially initiating insulin resistance in sufferers (22). Over time, this could put sufferers, particularly women (26) at a greater risk of obesity. (27 p.215).
Gut Health May be Key
Despite having a genetic tendency, attention to nutritional status and gut health may help lower the risk of migraine in predisposed individuals. Nutritional status and gut health may act as both a trigger to migraine as well as an intermediary in amplifying the intensity and frequency of an attack.
The gut can influence the brain and vice versa. They communicate together through the digestive nervous system, via the vagus nerve (28,29). An impaired vagus nerve can lead to “leaky gut” and a leaky gut can lead to inflammation including neuro inflammation. Gut bacteria also influences the brain by controlling inflammation and hormone production (30). There have been a number of trials which implicate gut dysbiosis in migraine, for example, infection with Helicobacter Pylori has been implicated as a risk factor for migraine and removal has resulted in its reduction (31).
Potential Dietary Approaches
There is no standard recommended dietary approach for migraine. Sufferers may have different risk factors, triggers and symptoms. However, the following plan may assist the sufferer achieve a consistently good balance of electrolytes to ensure sufficient energy, reducing inflammation as far as possible for good gut health, and providing the nutrients needed by the brain.
Food and Hydration
1. Gain a detailed understanding of dietary, lifestyle and environmental triggers, eliminating as far as possible those where sensitivity is suspected (32) (See box below).
2. Eat regularly to stabilise blood sugar balance. Variations in blood sugar can trigger migraines in some people, so smaller, more frequent meals may help. Ensure hydration throughout the day (see box below).
3. Increase consumption of high quality fats, particularly omega 3 and a reduction in processed and trans fats. Omega 3 fats are potentially important for brain function, healthy hormones, a healthy nervous system, and calming inflammation (33). They keep the membrane of neurons healthy, enabling brain cells to communicate with one another. Eat oily fish at least twice a week. In a study of 105 migraine patients, it was discovered that lower intakes of the omega 3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), correlated to a greater number of migraines (34). This is supported by a randomised controlled trial suggesting the targeted use of omega 3 and 6 fatty acids may be beneficial in migraine reduction (35).
4. Whilst not for everyone, consider a ketogenic diet (36), keeping carbohydrate intake under 5-10% of calories, eating moderate amounts of protein, and high fat (50-70% of calories), to encourage the production of ketones, a substance created by the liver. This helps to burn the body’s fat over glucose as the primary fuel for the body. Ketogenic diets frequently eliminate grains (especially gluten), which may improve gut health and migraine frequency and may help glucose sensitive sufferers to improve their insulin resistance (37). Include gut healthy foods such as kefir, kimchi, yogurt, jerusalem artichokes, onions, asparagus, cabbage family vegetables (38 p.3023). Ketogenic diets can also be anti-inflammatory as there is an emphasis on good quality green vegetables, fish and healthy fats rather than processed foods, refined sugar, hydrogenated fats, trans fats and grains (39).
5. Magnesium is another electrolyte required for the brain. Good sources are green leafy vegetables, green beans, broccoli, cabbage, peas. Fruits such as avocados, raspberries, fresh figs. Good fish sources are salmon, mackerel, tuna. Nuts, seeds and legumes are good sources of magnesium. Consider a magnesium supplement; there are migraine studies that have been beneficial at high dosages (40), but in the UK the safe upper limit is 400mg (41) which can often be an effective dose for migraine. It may be preferable to start at a low magnesium dose that is well absorbed (glycinate or malate) and increase over time to minimise effects such as diarrhoea (42 p376).
6. Riboflavin (B2) is required for providing energy to our brain cells. Eat foods containing vitamin B2 such as beef, tofu, spinach, mushrooms, avocados, eggs. Whilst deficiency is rare, there may be a beneficial effect of supplementation (40). In the UK, the recommended safe upper level is 43mg (41).
7. Sleep. Sufferers tend towards poor sleep (43). The Migraine Trust has some helpful information available to help practice good sleep hygiene (44).
Supporting sufferers is a process of understanding risk factors and triggers on an individualised basis, requiring detailed analysis and professional support. Using nutritional therapy may have potential in the management of migraine. It is important however that any nutritional approach is tailored to individual’s medical history, type of migraine symptoms, genetics, current nutritional health and any available test results. A registered nutritional therapist may be able to help sufferers tailor the right plan.
Removing Triggers
Triggers vary from person to person and recording details of migraine attacks may help the sufferer recognise triggers and warning signs as well as assessing if medication is working.
Records may include:
*Symptoms, including the type of headache and other symptoms eg anxiety, constipation
*Type of food and drink eaten
*Activities taken
*Factors such as weather, sleep, bowel movements, menstrual cycles
*Types of medication and vitamins
A migraine attack record is available to download from www.migrainedisorders.org
Importance of Good Hydration
*Hydration is key throughout the day.
*Drink a minimum of 9 glasses of water a day and always begin the day with a large glass of water.
*Every second glass of water should be taken with 1/8th tspn of salt and every 4th glass of water with a handful of potassium rich unsalted nuts and seeds.
The Stanton Protocol (45,46 p.66)
Further Reading
1. All Party Parliamentary Group. (2009) Headache Disorders - Not Respected, Not Resourced. Available from: http://www.migrainetrust.org/wp-content/uploads/2015/12/2010Mar APPGPHD_REPORT_Headache_Disorders-NotRespNotReso.pdf (Accessed: 15th September 2018).
2. The Migraine Trust. (n.d) Facts and figures - The Migraine Trust. [Available from: https://www.migrainetrust.org/about-migraine/migraine-what-is-it/facts-figures/(Accessed: 15th September 2018).
3. Stanton AA. Functional Prodrome in Migraines. (2016) J Neurol Disord . 04(01):1–5. Available from: http://www.esciencecentral.org/journals/functional-prodrome-in-migraines-2329-6895-1000256.php?aid=67534 (Accessed 15th September 2018).
4. Migraine Action. (n.d) What Is Migraine Aura? Available from: http://www.migraine.org.uk/information/factsheets/what-is-migraine-aura/(Accessed 15th September 2018).
5. Triggers | Association of Migraine Disorders. (n.d) Available from: http://www.migrainedisorders.org/what-is-a-migraine-disorder/triggers (Accessed 15th Septemberr 2018).
6. Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. (2015) J Neurosci; 35(17):6619–29. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25926442 (Accessed 15th September 2018).
7. The Migraine Association. (2014) Migraine Pathophysiology - In depth - YouTube. Available from: https://www.youtube.com/watch?v=pUbXB8vT8fY&t=927s (Accessed 15th September 2018).
8. Amin FM, Asghar MS, Hougaard A, Hansen AE, Larsen VA, de Koning PJH, et al. (2013). Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study. Lancet Neurol;12(5):454–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23578775 (Accessed 15th September 2018).
9. Laino C. (2003) New Insights into Triptans & Migraines. Neurol Today;3:22. Available from: https://journals.lww.com/neurotodayonline/Fulltext/2003/06001/NEW_INSIGHTS_INTO_TRIPTANS_AND_MIGRAINE.10.aspx (Accessed 16th September 2018).
10. Noseda R, Kainz V, Borsook D, Burstein R. (2014) Neurochemical pathways that converge on thalamic trigeminovascular neurons: potential substrate for modulation of migraine by sleep, food intake, stress and anxiety. PLoS One;9(8):e103929. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25090640 (Accessed: 15th September 2018).
11. Zhang L-M, Dong Z, Yu S-Y. (2016) Migraine in the era of precision medicine. Ann Transl Med;4(6):105. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27127758 (Accessed:16th September 2018)
12. Liu H, Ge H, Xiang J, Miao A, Tang L, Wu T, et al. (2015) Resting state brain activity in patients with migraine: a magnetoencephalography study. J Headache Pain;16:525. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25968099 (Accessed: 16th September 2018)
13. Malhotra R. (2016) Understanding migraine: Potential role of neurogenic inflammation. Ann Indian Acad Neurol;19(2):175–82. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27293326 (Accessed:17th September 2018)
14. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. (2017) Pathophysiology of Migraine: A Disorder of Sensory Processing. Physiol Rev;97(2):553–622. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28179394 (Accessed 15th September 2018)
15. Stanton AA. (2017) Fighting the Migraine Epidemic. Complete Guide. How to Treat & Prevent Migraines without Medications. 2nd edn. North Charleston, South Carolina: Create Space Independent.
16. Stanton AA. (2017) Fighting the Migraine Epidemic. Complete Guide. How to Treat & Prevent Migraines without Medications. 2nd edn. North Charleston, South Carolina: Create Space Independent. p.87.
17. Friedrich T, Tavraz NN, Junghans C. (2016) ATP1A2 Mutations in Migraine: Seeing through the Facets of an Ion Pump onto the Neurobiology of Disease. Front Physiol;7:239. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27445835 (Accessed: 18th September 2018).
18. Pogoda JM, Gross NB, Arakaki X, Fonteh AN, Cowan RP, Harrington MG. (2016) Severe Headache or Migraine History is Inversely Correlated With Dietary Sodium Intake: NHANES 1999-2004. Headache;56(4):688–98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27016121 (Accessed: 18th September 2018).
19. de Baaij JHF, Hoenderop JGJ, Bindels RJM. (2015) Magnesium in Man: Implications for Health and Disease. Physiol Rev; 95(1):1–46. Available from: http://www.physiology.org/doi/10.1152/physrev.00012.2014(Accessed: 16th September 2018).
20. Schwedt TJ. (2013). Multisensory integration in migraine. Curr Opin Neurol;26(3):248–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23591684 (Accessed: 18th September 2018).
21. Siva ZO, Uluduz D, Keskin FE, Erenler F, Balcı H, Uygunoğlu U, et al.(2017) Determinants of glucose metabolism and the role of NPY in the progression of insulin resistance in chronic migraine (Abstract). Cephalalgia;033310241774892. Available from: http://journals.sagepub.com/doi/10.1177/0333102417748928 (Accessed 18th September 2018).
22. Blázquez E, Velázquez E, Hurtado-Carneiro V, Ruiz-Albusac JM. (2014) Insulin in the brain: its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer’s disease. Front Endocrinol (Lausanne);5:161. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25346723 (Accessed: 18th September 2018).
23. Sachdev A, Marmura MJ. (2012) Metabolic syndrome and migraine. Front Neurol;3:161. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23181051 (Accessed: 18th September 2018).
24. Stanton AA. (2017) Fighting the Migraine Epidemic. Complete Guide. How to Treat & Prevent Migraines without Medications. 2nd edn. North Charleston, South Carolina: Create Space Independent. p.132.
25. Chen C, Wang S, Hu Q, Zeng L, Peng H, Liu C, et al. (2018) Voltage-Gated Na+ Channels are Modulated by Glucose and Involved in Regulating Cellular Insulin Content of INS-1 Cells. Cell Physiol Biochem;45(2):446–57. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29402835 (Accessed: 18th September 2018).
26. Gupte AA, Pownall HJ, Hamilton DJ. Estrogen: an emerging regulator of insulin action and mitochondrial function. (2015) J Diabetes Res;2015:916585. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25883987 (Accessed 18th September 2018).
27. Stanton AA. (2017) Fighting the Migraine Epidemic. Complete Guide. How to Treat & Prevent Migraines without Medications. 2nd edn. North Charleston, South Carolina: Create Space Independent. p.215.
28. Amar AP, Apuzzo ML. (2009) Vagus nerve stimulation - an overview | ScienceDirect Topics. J Neuromodulation. Available from: https://www.sciencedirect.com/topics/neuroscience/vagus-nerve-stimulation (Accessed 1st October 2018).
29. Eskandari F, Webster JI, Sternberg EM. (2003) Neural immune pathways and their connection to inflammatory diseases. Arthritis Res Ther;5(6):251–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14680500 (Accessed 1st October 2018).
30. Rea K, Dinan TG, Cryan JF. (2016) The microbiome: A key regulator of stress and neuroinflammation. Neurobiol Stress;4:23–33. Available from: https://www.sciencedirect.com/science/article/pii/S2352289515300370 (Accessed 1st October 2018).
31. Tunca A et al. (2004) Is Helicobacter Pylori a Risk Factor for Migraine? Available from: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.470.8217&rep=rep1&type=pdf (Accessed: 2nd October 2018).
32. Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, Baykan B. (2010) Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia;30(7):829–37. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20647174 (Acessed 1st October 2018).
33. Yan Y, Jiang W, Spinetti T, Tardivel A, Castillo R, Bourquin C, et al. (2013) Omega-3 Fatty Acids Prevent Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome Activation. Immunity;38(6):1154–63. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1074761313002422 (Accessed:1st October 2018).
34. Sadeghi O, Maghsoudi Z, Khorvash F, Ghiasvand R, Askari G. (2015) The relationship between different fatty acids intake and frequency of migraine attacks. Iran J Nurs Midwifery Res [Internet]. 2015 [cited 2018 Oct 9];20(3):334–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26120333 (Accessed 1st October 2018).
35. Ramsden CE, Faurot KR, Zamora D, Suchindran CM, Macintosh BA, Gaylord S, et al. (2013) Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial. Pain;154(11):2441–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23886520 (Accessed: 18th September 2018)
36. Di Lorenzo C, Coppola G, Bracaglia M, Di Lenola D, Evangelista M, Sirianni G, et al. (2016) Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J Headache Pain;17:58. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27245682 (Accessed: 20th September 2018).
37. Toribio-Mateas M. (2018) Harnessing the Power of Microbiome Assessment Tools as Part of Neuroprotective Nutrition and Lifestyle Medicine Interventions. Microorganisms;6(2). Available from: http://www.ncbi.nlm.nih.gov/pubmed/29693607 (Accessed: 19th September 2018)
38. Enders G. (2015) Gut: The Inside Story of our Body’s Most Under-Rated Organ. 2st edn. London. Scribe Publications. (Kindle Version) p3023.
39. de Punder K, Pruimboom L. (2013) The dietary intake of wheat and other cereal grains and their role in inflammation. Nutrients;5(3):771–87. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23482055 (Accessed 30th September 2018).
40. Gaul C, Diener H-C, Danesch U, Migravent® Study Group on behalf of the MS. (2015). Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial. J Headache Pain;16:516. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25916335 (Accessed 15th September 2018).
41. Stewart A. (2018) Safe Upper Levels and Guidance Levels for Vitamins and Minerals. Available from: http://www.stewartnutrition.co.uk/supplement_safety/safe_upper_levels_and_guidance_levels_for_vitamins_and_minerals.html (Accessed 9th October 2018).
42. Lipski E. (2012) Digestive Wellness. 4th edn. London. McGraw-Hill. p.376.
43. Lin Y-K, Lin G-Y, Lee J-T, Lee M-S, Tsai C-K, Hsu Y-W, et al. (2016) Associations Between Sleep Quality and Migraine Frequency: A Cross-Sectional Case-Control Study. Medicine (Baltimore);95(17):e3554. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27124064 (Accessed: 9th October 2018).
44. Sleep and migraine - The Migraine Trust (n.d). Available from: https://www.migrainetrust.org/living-with-migraine/coping-managing/sleep/ (Accessed: 9th October 2018).
45. Stanton AA. The Stanton Migraine Protocol (n.d). Available from: https://stantonmigraineprotocol.com/ (Accessed: 18th September 2018)
46. Stanton AA. (2017) Fighting the Migraine Epidemic. Complete Guide. How to Treat & Prevent Migraines without Medications. 2nd edn. North Charleston, South Carolina: Create Space Independent. p.66.