---

Migraine headaches, as any sufferer will tell you, can be debilitating, painful, and inconvenient, affecting 17% of females, 6% of males. While over a dozen genetic markers have been identified that predispose to migraine headaches, this condition is clearly multifactorial, i.e., there are typically a combination of factors at work, factors that are genetic, environmental, nutritional, and hormonal. It also means that, rather than “treating” headaches with drugs that only provide pain relief or address a single aspect of the condition (e.g., vessel spasm or pain relief), trying to pinpoint the causal factors that can be corrected may be a more rational approach.


Overview

---

People with migraine headaches are susceptible to other health conditions more than would be expected by chance, such as high blood pressure, sinus inflammation/infections, asthma, insomnia and sleep disorders, mood disorders, and fibromyalgia. In particular, gastrointestinal disorders have been associated with migraines, including Helicobacter pylori infection, irritable bowel syndrome, gastroparesis, hepatobiliary diseases, celiac disease and dysbiosis. This suggests either a shared cause for migraines and gastrointestinal disorders and/or overlap involving conditions such as dysbiosis/small intestinal bacterial overgrowth. The frequency of overlap of migraines headaches with irritable bowel syndrome (IBS) may be especially revealing, given that as many as 84% of people with IBS also have small intestinal bacterial overgrowth (SIBO), an association that has caused some experts to believe that IBS and SIBO are one and the same condition.

In this Undoctored Advanced Concepts: Preventing Migraine Headaches, we shall discuss several strategies that have been shown to reduce the frequency and severity of migraine episodes. These strategies are meant to correct the factors that allow migraine headaches to emerge and are therefore not meant to be acute treatment for active headache, but as strategies to consider to prevent future episodes.

Based on both clinical trials and substantial anecdote, several basic practices have been shown to reduce severity/frequency of migraines. Such practices include:

• Reduced carbohydrate intake that leads to avoidance of reactive hypoglycemia (low blood sugars that follow high blood sugars—low blood sugar rarely occurs on its own) reduces migraine frequency.
• Avoidance of caffeine.
• Avoidance of vasoactive factors—-such as tyramine and pheylethyalmine from foods such as wine, cheese, chocolate, and citrus fruits.
• Avoidance of aspartame—An effect of chronic, less with acute, ingestion. (A reflection of the dysbiosis provoked by aspartame?)
• Aerobic exercise—Aerobic exercise has been shown repeatedly to reduce migraine frequency by approximately 40% with the effect beginning within 4 weeks, although the mechanisms is unclear.

There are associations of migraines with other conditions, associations that may suggest shared causes, as well as solutions:

Migraines and celiac disease/gluten sensitivity

It has been established that people with celiac disease also have a higher incidence of migraine headaches, as well as abnormalities of brain white matter seen on MRI. In one small study of people with both gluten sensitivity and migraine headaches, 90% obtained relief from headaches by following a gluten-free diet. (We have observed a similar high rate of relief in the worldwide Wheat Belly experience of grain elimination.)

Migraines and food sensitivities

A preliminary study of participants with both migraine and IBS suggested that IgG food sensitivity testing followed by elimination of foods associated with high IgG levels reduced headache severity, duration, and need for medication by half. Other studies have demonstrated reduction in frequency of migraines with various food eliminations, most notably wheat; oranges; eggs; coffee, tea, and chocolate; dairy products; beef; corn products; yeast-containing products; mushrooms; peas.

However, we need to keep in mind that many food sensitivites are acquired due to factors that increase intestinal permeability, such as grain consumption and the development of small intestinal bacterial overgrowth, in which case the real solution is not avoidance of food associated with higher antibody levels, but correction of the cause.

Migraines and magnesium

Because part of the migraine headache process is vasospasm, i.e., spasm of the arteries of the brain, a process that can be provoked by magnesium deficiency that modulates arterial tone, magnesium administration has been investigated as a potential means of treating and/preventing migraines. People with migraines also have lower blood levels of magnesium than people without migraines. Unfortunately, most studies have used doses of magnesium, both intravenous and oral, that we would regard as too low, even trivial. Nonetheless, while study results have varied, the studies as a whole have demonstrated reduction and relief of migraine headaches administered both acutely and chronically.

Magnesium restoration is therefore among the cornerstones of the Undoctored approach to migraine relief. While magnesium is already a component of the Undoctored Wild, Naked, Unwashed program, because migraines can be so debilitating and many people are eager for relief, coupled with the slow process of magnesium restoration that typically requires years (because of the limiting factor of gastrointestinal tolerance with moderate to higher doses resulting in diarrhea), we stress magnesium restoration with our recipe for Magnesium Water, working to increase tolerance and increasing the dose over time. (See discussion below.) Assessment of magnesium status is also flawed, since most magnesium is stored in bone and inside the tissues and cells of the body, therefore not well reflected by serum or RBC levels that are commonly tested and underestimate the severity of deficiency (though if low levels are measured, deficiency is profound). Magnesium toxicity/overdose is also exceptionally rare, developing only in people who purposefully ingest large amounts of magnesium-based antacids over a prolonged period. For these reasons, we push the limits of magnesium restoration to achieve migraine relief, as well as to obtain other benefits including reduction of blood pressure and strengthening of bone/protection from osteoporosis.

Migraines, homocysteine, and MTHFR C677T

Higher homocysteine blood levels are associated with migraine headaches, while reduction of homocysteine with B vitamins (folates, B12, B6, and B2) correlates with reduction in severity and intensity of migaines. (Note that higher blood homocysteine levels also predict greater likelihood of depression and cognitive impairment/dementia.) In addition, the fairly common MTHFR gene variant, C677T, carried by 12-25% of people, causes poor absorption of folate (vitamin B9), reflected by increased blood levels of homocysteine. People with migraines have a greater likelihood of carrying the C677T gene variant and are therefore more susceptible to the effects of low folate and higher homocysteine levels.

In one study, for example, a combination of folic acid 2 mg + vitamin B6 25 mg + vitamin B12 400 mcg vs. placebo was shown to reduce migraine frequency by 75%, severity by 25%, along with 39% reduction in homocysteine from a starting level of 10.8 micromol/L (a level regarded as “normal” in most lab reports). Benefits were most marked in carriers of the MTHFR C677T genotype. Riboflavin has also been shown to reduce migraines; see below in the discussion re: mitochondrial dysfunction.

Unfortunately, the methyl-form of folate that is more effective in increasing blood folate levels in people with MTHFR C677T has not been explored in any clinical study, but should be expected to be more effective in both reducing homocysteine and frequency/severity of migraine headaches than synthetic folic acid or folates and side-steps the suspected increased cancer rate that may occur with folic acid (due to higher blood levels of unmetabolized folic acid).    Interestingly, SIBO is not uncommonly associated with poor absorption of folate and B12, potentially magnifying deficiency of these nutrients, especially in those with the MTHFR C677T variant.

Migraines and mitochondrial dysfunction

Several nutrients that participate in mitochondrial energy generation have been shown to reduce severity/frequency of migraines, most notably coenzyme Q10 and riboflavin.

Doses of coenzyme Q10 (CoQ10) as ubiquinone that provide headache relief range from 100 to 300 mg per day. The ubiquinol form of CoQ10, as compared to the more common ubiquinone, is better absorbed and can allow lower doses to be used, e.g., 50-100 mg per day. There may also be advantages in more than once-per-day dosing (doses divided into twice- or three-times-per-day).

Riboflavin, vitamin B2, a factor in mitochondrial energy generation (as well as its contribution to homocysteine, above), has been shown in several clinical studies to reduce frequency and severity of migraines. (Because riboflavin is found in higher quantities in organ meats, especially liver, as well as meats and eggs, could this apparent increased need for riboflavin simply be a reflection of our modern failure to consume organ meats?) The dose most commonly used in clinical trials has been 400 mg, but 100-200 mg per day has also shown effectiveness.

The combination of CoQ10 with riboflavin appears to be more effective than either alone.

Migraines, H. pylori, dysbiosis, and small intestinal bacterial overgrowth

There is axcess of H. pylori infection of the stomach in people with migraines. A meta-analysis of five studies and over 900 participants demonstrated that H. pylori was present in 45% of people with migraines, 33% in those without migraines. Migraine sufferers also have higher levels of antibodies (IgM and IgG) against H. pylori, suggesting a uniquely amplified immune response against this organism, though for unclear reasons. Accordingly, antibiotic treatment of H. pylori infection yields reduction in migraine frequency/severity in approximately a quarter of people treated.

There is another layer to this conversation, however. H. pylori is also a common cause for hypo- or achlorhydria, i.e., low or absent stomach acid. Stomach acid is an effective barrier to microorganisms that can ascend up from the lower intestine. With inadequate stomach acid, bacteria can more readily ascend up from the colon, ileum, then jejunum and duodenum and, finally, the stomach—this is small intestinal bacterial overgrowth (SIBO). You may recall from our discussions about SIBO that irritable bowel syndrome (IBS) and SIBO are likely one and the same, or at least have extensive overlap and that up to 84% of people with IBS have SIBO, even with flawed methods of diagnosis. It therefore stands to reason that people with migraine headaches who have markedly greater likelihood of having IBS (and vice versa) are also very likely to have SIBO. This therefore suggests that addressing SIBO may be another path to follow to obtain relief from migraine headaches. 

Proposed regimen for migraine prevention

In addition to the basic practices listed above that are worth exploring for anyone with migraine headaches, the elements of the Undoctored Wild, Naked, Unwashed program that have beneficial effects on migraine headaches include:

Grain elimination/carb limitation

There are several ways in which our dietary approach can reduce, sometimes eliminate, migraine headaches: weight loss and reduction in insulin resistance, elimination of hyperglycemia/hypoglycemia cycles provoked by grains and sugars, removal of the gliadin protein of wheat and related grains (“gluten-free”), restoration of magnesium absorption through elimination of grain phytates. 

Magnesium

Magnesium is front and center, the centerpiece of any migraine-preventing effort after the diet. You are strongly urged to use Magnesium Water as the preferred source for magnesium, as it is the most absorbable form available, magnesium bicarbonate. Because it requires years to restore tissue magnesium levels, anyone with migraines ideally uses the Magnesium Water form that accelerates magnesium repletion.

We begin with four ounces (1/2 cup) twice per day. Each serving provides 90 mg of elemental magnesium; four ounces twice per day therefore yields 180 mg per day. It is important to increase the dose over time to eventually achieve 8 ounces (one cup) twice per day to provide 360 mg per day.

Yield : 2 liters

2-liter bottle of seltzer/carbonated water (not tonic water, i.e., containing no sugar) 3 tablespoons unflavored milk of magnesia Naturally flavored extracts and/or sweetener

Uncap the seltzer and pour off a few tablespoons. Shake the milk of magnesia and pour out 3 tablespoons. (Most brands come with a handy little measuring cup that works perfectly.) Pour the milk of magnesia into the seltzer slowly, followed by the extract and sweetener.

Cap the bottle securely, and shake until all the sediment has dissolved. Let the mixture sit for 15 minutes and allow to clarify. If any sediment remains, shake again. Drink as instructed above.

Vitamin D

By itself, vitamin D appears to not be effective for migraine prevention. However, a subset of people experience improved responsiveness to other therapies when vitamin D is added, an effect that is likely driven by genetic variation.

Fish oil

As a sole agent, the omega-3 acids have only a modest effect that appears to mostly achieve a reduction in duration of migraines, but not in frequency or duration. However, in the context of all other strategies, the benefits may be magnified.

Correction of dysbiosis

The basic Undoctored bowel flora-cultivating efforts of introducing a high-potency, multi-species probiotic, fermented foods, and daily prebiotic fibers corrects dysbiosis in most people. However, if you prove intolerant to prebiotic fibers, you will need to explore SIBO; more on SIBO can be found in the Undoctored Inner Circle video library. There is also an Undoctored Protocol for SIBO.

If the above strategies do not provide full relief from migraine headaches, consider:

Homocysteine reduction

MTHFR If homocysteine is elevated, particularly above 8 micromol/L, methylfolate 800 mcg + methyl-B12 1000 mcg can be considered. Also consider 50 mg of pyridoxal-5’-phosphate (a form of vitamin B6) and riboflavin 100-400 mg per day. The above regimen should also be considered if the MTHFR C677T variant is identified.

Mitochondrial strategies

Taking both riboflavin and CoQ10 in combination is likely more effective than either alone.

Riboflavin (vitamin B2) 100-400 mg per day Coenzyme Q10 (ubiquinone)—100 mg per day, increase to 300 mg per day to gauge effect. If ubiquinol is used, 50-100 mg per day is the dose. Ideally, ubiquinone or ubiquinol doses are divided into two or three doses.   H. pylori and SIBO Undergo assessment for H. pylori, followed by eradication therapy Undergo assessment for SIBO or initiate empiric therapy (as discussed in the SIBO Undoctored Protocol)


Selected References

Migraines and metabolic distortions Verrotti A, Carotenuto M, Altieri L et al. Migraine and obesity: metabolic parameters and response to a weight loss programme. Pediatr Obes. 2015;10:220–5.

Gluten/grains and migraines Bürk K, Farecki ML, Lamprecht G et al. Neurological symptoms in patients with biopsy proven celiac disease. Mov Disord. 2009;24:2358–62.

Hadjivassiliou M, Grünewald RA, Lawden M et a;. Headache and CNS white matter abnormalities associated with gluten sensitivity. Neurology. 2001;56:385–388.

Lionetti E, Francavilla R, Maiuri L et al. Headache in pediatric patients with celiac disease and its prevalence as a diagnostic clue. J Pediatr Gastroenterol Nutr. 2009;49:202–7.   Migraines and exercise Irby MB, Bond DS, Lipton RB et al. Aerobic Exercise for Reducing Migraine Burden: Mechanisms, Markers, and Models of Change Processes. Headache 2016 Feb;56(2):357-69.

Migraines and magnesium Chiu HY, Yeh TH, Huang YC, Chen PY. Effects of Intravenous and Oral Magnesium on Reducing Migraine: A Meta-analysis of Randomized Controlled Trials. Pain Physician 2016 Jan;19(1):E97-112.

Mauskop A, Varughese J. Why all migraine patients should be treated with magnesium. J Neural Transm 2012 May;119(5):575-9.

Omega-3 fatty acids and migraines Maghsoumi-Norouzabad L, Mansoori A, Abed R, Shishehbor F. Effects of omega-3 fatty acids on the frequency, severity, and duration of migraine attacks: A systematic review and meta-analysis. Nutr Neurosci 2017 Jun 30:1-10.

Vitamin D and migraines Cayir A, Turan MI, Tan H. Effect of vitamin D therapy in addition to amitriptyline on migraine attacks in pediatric patients. Braz J Med Biol Res 2014 Apr;47(4):349-54.

Mitochondrial dysfunction and migraines Boehnke C, Reuter U, Flach U et al. High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre. Eur J Neurol. 2004;11(7):475–77.

Langsjoen PH, Langsjoen AM. Comparison study of plasma coenzyme Q10 levels in healthy subjects supplemented with ubiquinol versus ubiquinone. Clin Pharmacol Drug Dev 2014 Jan;3(1):13-7.

Sandor PS, Di Clemente L, Coppola G et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology 2005 Feb 22;64(4):713-5.

Shoeibi A, Olfati N Soltani Sabi M et al. Effectiveness of coenzyme Q10 in prophylactic treatment of migraine headache: an open-label, add-on, controlled trial. Acta Neurol Belg 2017 Mar;117(1):103-9.

Yorns WR, Hardison HH. Mitochondrial dysfunction in migraine. Semin Pediatr Neurol  2013 Sep;20(3):188-93.

Migraines, homocysteine, and MTHFR Lea R, Colson N, Quinlan S 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.

Menon S, Lea R, Roy B et al. Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation. Pharmacogenet Genomics 2012;22(10):741–9.

Oterino A, Toriello, Valle N et al. The relationship between homocysteine and genes of folate-related enzymes in migraine patients. Headache 2010 Jan;50(1):99-168.

IBS and migraine headaches Aydinlar EI, Dikmen PY, Tiftikci A et al. IgG-based elimination diet in migraine plus irritable bowel syndrome. Headache. 2013;53:514–25.

Chang FY, Lu CL. Irritable bowel syndrome and migraine: bystanders or partners? J Neurogastroenterol Motil 2013 Jul;19(3):301-11.

Cole JA, Rothman KJ, Cabral HJ et al. Migraine, fibromyalgia, and depression among people with IBS: a prevalence study. BMC Gastroenterol. 2006;6:26.

Lau CI, Lin CC, Chen WH et al. Association between migraine and irritable bowel syndrome: a population-based retrospective cohort study. Eur J Neurol. 2014;21:1198–1204.

H pylori and migraine headaches Ansari B, Basiri K, Meamar R et al. Association of Helicobacter pylori antibodies and severity of migraine attack. Iran J Neurol. 2015;14:125–9.

Savi L, Ribaldone DG, Fagoonee S, Pellicano R. Is Helicobacter pylori the infectious trigger for headache?: A review. Infect Disord Drug Targets. 2013;13:313–7.

Su J, Zhou XY, Zhang GX. Association between Helicobacter pylori infection and migraine: a meta-analysis. World J Gastroenterol. 2014;20:14965–72.

Dysbiosis, probiotics, and migraines de Roos NM, Giezenaar CG, Rovers JM et al. The effects of the multispecies probiotic mixture Ecologic®Barrier on migraine: results of an open-label pilot study. Benef Microbes 2015;6:641–6

---