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I recommend you read my article What Is Functional Medicine?’ before reading this article. It will help you get the most out of this article on migraines.

Migraines are a common experience for people with chronic fatigue.

This article takes you on a comprehensive overview of the underlying causes of migraines. As always, it is important to appreciate migraines are the symptom….the manifestation of an imbalance somewhere in the body. The imbalance will be personal to each individual and thus require a personal treatment plan. As you will see, digestive imbalance, food sensitivities, mitochondrial dysfunction, nutrient deficiencies and hormonal imbalances are all potential causes. This is why taking a Functional Medicine approach is such a powerful approach.


A great paper discussed the relationship between the gut and migraines.

Recent studies suggest that migraine may be associated with gastrointestinal (GI) disorders, including irritable bowel syndrome (IBS), inflammatory bowel syndrome, and celiac disease.

Possible underlying mechanisms of migraine and GI diseases could be increased gut permeability and inflammation. Therefore, it would be worthwhile to investigate these mechanisms further in migraine patients.

The brain and the GI tract are strongly connected via neural, endocrine, and immune pathways. The communication occurs in two directions, not only from the brain to the gut but also the other way around. This recent finding on the role of the gut microbiota in the gut-brain axis suggests that the gut microbiota can be associated with brain functions and neurological diseases like migraine.

An Elimination Diet

Experimental evidence for an association between IBS and migraine comes from a study in which an IgG-based elimination diet was given to migraine patients with IBS. Twenty-one patients were included in the double blind, randomized, controlled, cross-over clinical trial with usual diet, elimination diet, and provocation diet. Compared with baseline, the elimination diet was associated with a significant reduction in migraine attack count, duration and severity. Also a significant reduction in IBS complaints was observed, demonstrating an association between the two diseases.

Coeliac Disease

In patients who suffer from celiac disease, the immune system develops an autoimmune reaction against gliadin, the main protein in gluten. This inflammatory reaction is associated with intestinal damage, including dysfunction of the tight junctions resulting in an increased intestinal permeability. Celiac disease has been associated with migraine headache in case–control studies.

The paper concluded: This overview of the literature suggests the existence of a rather strong relationship between GI disorders and migraine. One of the links between inflammatory diseases and migraine are enhanced pro-inflammatory immune responses. In intestinal disorders characterized by an increased intestinal permeability like IBS, IBD, and celiac disease enhanced pro-inflammatory immune responses have been reported. Enhanced levels of pro-inflammatory cytokines like tumor necrosis factor alpha and interleukin 1β in serum of migraine patients have been found during migraine attacks. These cytokines can act on the nociceptors of the trigeminal nerve, causing migraine. Also statistical significant associations have been reported between migraine and a wide range of inflammatory disorders like asthma, obesity, metabolic syndrome, allergies, and GI diseases. A strong trigger of pro-inflammatory immune responses is the leakage of lipopolysaccharides (LPS) from the intestinal lumen into the circulation. Enhanced levels of LPS can enter the circulation when the intestinal permeability is increased. Depending on genetic susceptibility, pro-inflammatory responses can occur in different parts of the body, e.g., in case of migraine on the nociceptors of the trigeminal nerve.


As probiotics may play a role in maintaining or improving gut barrier function in human beings, they can have a beneficial effect in migraine patients with an enhanced intestinal permeability as well. So far, no clinical randomized controlled trials have been published where migraine patients received nutritional therapy with probiotics. An uncontrolled study reported the effects of a combination of different probiotics (Lactobacillus acidophilus, Lactobacillus bulgaricus, Enterococcus faecium, and Bifidobacterium bifidum) with vitamins, minerals, micronutrients, and herbs in 40 migraine patients. At the onset of this study, the participants had a mean quality of life score of 38 [Medical Outcomes Trust Migraine Specific Quality of Life (MSQ) Questionnaire] and after 90 days of treatment their mean quality of life score was risen to 76. Sixty percent of the migraine patients experienced almost total relief from migraine attacks and they reported quality of life scores between 80 and 100.


Another paper stated: In conclusion, identification of environmental factors (including dietary factors) that consistently trigger migraine in some subjects may be helpful to reduce attacks frequency. The biological mechanism by means of triggers in general and food in particular precipitate migraine attacks remains obscure.

The American Nutrition Association list the below foods as those that may trigger migraine attacks
• Aged or strong cheese
• Cured meats (hot dogs, bacon, ham, and salami)
• Citrus fruits
• Fatty or fried foods
• Chocolate, nuts
• Monosodium glutamate
• Food dyes, additives
• Pickled herring, chicken livers
• Ice cream
• Yogurt, sour cream
• Meat and vegetable extracts
• Pork and seafood
• Canned figs, broad beans, tomatoes
• Caffeine-containing drinks (coffee, tea, all “cola” soft drinks)
• Caffeine withdrawal
• Alcoholic drinks (red wine, beer)
• Aspartame, nitrites, sulfites


An abstract from a recent paper states: Magnesium, the second most abundant intracellular cation, is essential in many intracellular processes and appears to play an important role in migraine pathogenesis. Routine blood tests do not reflect true body magnesium stores since <2% is in the measurable, extracellular space, 67% is in the bone and 31% is located intracellularly. Lack of magnesium may promote cortical spreading depression, hyperaggregation of platelets, affect serotonin receptor function, and influence synthesis and release of a variety of neurotransmitters. Migraine sufferers may develop magnesium deficiency due to genetic inability to absorb magnesium, inherited renal magnesium wasting, excretion of excessive amounts of magnesium due to stress, low nutritional intake, and several other reasons. There is strong evidence that magnesium deficiency is much more prevalent in migraine sufferers than in healthy controls. Double-blind, placebo-controlled trials have produced mixed results, most likely because both magnesium deficient and non-deficient patients were included in these trials. This is akin to giving cyanocobalamine in a blinded fashion to a group of people with peripheral neuropathy without regard to their cyanocobalamine levels. Both oral and intravenous magnesium are widely available, extremely safe, very inexpensive and for patients who are magnesium deficient can be highly effective. Considering these features of magnesium, the fact that magnesium deficiency may be present in up to half of migraine patients, and that routine blood tests are not indicative of magnesium status, empiric treatment with at least oral magnesium is warranted in all migraine sufferers.

Other Nutrients

Migraine is the most common form of headache disorder globally. The etiology of migraine is multifactorial, with genetic components and environmental interactions considered to be the main causal factors. Some researchers postulate that deficits in mitochondrial energy reserves can cause migraine or an increase in homocysteine levels can lead to migraine attacks; therefore, vitamins could play a vital role in migraine prevention.

For instance, riboflavin influences mitochondrial dysfunction and prevents migraine. Genes such as flavoenzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma levels of homocysteine and migraine with aura. Homocysteine catalyzation requires the presence of vitamins B6, B12, and folic acid, which can decrease the severity of migraine with aura, making these vitamins potentially useful prophylactic agents for treating migraine with aura. Menstrual migraine, on the other hand, is associated with increased prostaglandin (PG) levels in the endometrium, indicating a role for vitamin E, which is an anti-PG.


Vitamin C can also be used as a scavenger of reactive oxygen species for treating neurogenic inflammation in migraine patients. This paper reviews possible therapies based on vitamin supplementation for migraine prophylaxis, focusing on migraine with aura and menstrual migraine.


Mitochondria may also be involved. Migraine is the most frequent type of headache in children. In the 1980s, scientists first hypothesized a connection between migraine and mitochondrial (mt) disorders. More recent studies have suggested that at least some subtypes of migraine may be related to a mt defect. Different types of evidence support a relationship between mitochondria (mt) and migraine:

(1) Biochemical evidence: Abnormal mt function translates into high intracellular penetration of Ca(2+), excessive production of free radicals, and deficient oxidative phosphorylation, which ultimately causes energy failure in neurons and astrocytes, thus triggering migraine mechanisms, including spreading depression. The mt markers of these events are low activity of superoxide dismutase, activation of cytochrome-c oxidase and nitric oxide, high levels of lactate and pyruvate, and low ratios of phosphocreatine-inorganic phosphate and N-acetylaspartate-choline.

(2) Morphologic evidence: mt abnormalities have been shown in migraine sufferers, the most characteristic ones being direct observation in muscle biopsy of ragged red and cytochrome-c oxidase-negative fibers, accumulation of subsarcolemmal mt, and demonstration of giant mt with paracrystalline inclusions.

(3) Genetic evidence: Recent studies have identified specific mutations responsible for migraine susceptibility. However, the investigation of the mtDNA mutations found in classic mt disorders (mt encephalomyopathy with lactic acidosis and stroke-like episodes, myoclonus epilepsy with ragged red fibers, Kearns-Sayre syndrome, and Leber hereditary optic neuropathy) has not demonstrated any association. Recently, 2 common mtDNA polymorphisms (16519C→T and 3010G→A) have been associated with pediatric cyclic vomiting syndrome and migraine. Also, POLG mutations (eg, p.T851 A, p.N468D, p.Y831C, p.G517V, and p.P163S) can cause disease through impaired replication of mtDNA, including migraine. Further studies to investigate the relationship between mtDNA and migraine will require very large sample sizes to obtain statistically significant results.

(4) Therapeutic evidence: Several agents that have a positive effect on mt metabolism have shown to be effective in the treatment of migraines. The agents include riboflavin (B2), coenzyme Q10, magnesium, niacin, carnitine, topiramate, and lipoic acid. Further study is warranted to learn how mt interact with other factors to cause migraines. This will facilitate the development of new and more specific treatments that will reduce the frequency or severity or both of this disease.



Current literature has consistently demonstrated that headache, in particular migraine, is more prevalent in women as compared with men, specifically during reproductive years. Recent studies have found differences in headache characteristics, central nervous system anatomy, as well as functional activation by fMRI between the sexes in migraine patients. Although the cause underlying these differences is likely multifactorial, considerable evidence supports an important role for sex hormones. Recent studies continue to support that MRM is precipitated by drops in estrogen concentrations, and minimizing this decline may prevent these headaches.

Genetics & Methylation

One paper discussed how migraines are a neurovascular disease that has classically been attributed to multifactorial aetiologies, with genetic components and environmental interactions considered the main influence. Genes such as flavoenzyme 5, 10- methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma homocysteine levels. This elevation in homocysteine results in an array of metabolic disorders and increased risk of complex diseases, including migraine. Catalysation of homocysteine requires the presence of vitamins B6, B12 and folate. Deficiencies in these cofactor vitamins result in hypomethylation, which triggers migraine. Because migraine predominantly affects females, it is hypothesised that fluctuating oestrogen levels, which are governed by oestrogen receptor 1 polymorphisms, are important. Another important factor is homocysteine, the production of which is dependent upon MTHFR and B vitamins. Gene expression is modulated through epigenetic mechanisms, which involve methionine. Additionally, folate plays a major role in DNA synthesis. We propose that vitamin B intake, coupled with MTHFR and oestrogen receptor 1 polymorphisms, causes differential DNA methylation and gene expression that may contribute to the occurrence of migraine.


As you can see it is important to take a systems based approached to optimising health – many systems may be involved.

If you struggle with migraines and would like support then don’t hesitate to contact me.