Chiropractor

Introduction
Migraine headaches affect 18% of women and 6.5% of men in the United States of America, and almost half of these people are undiagnosed or undertreated.5  This familial disorder has been identified as consisting of two major disorders: migraine with aura and migraine without aura. 14  A migraine headache is characterized by a periodic pounding headache that is often unilateral and can many times be associated with other symptoms such as phonophobia, photophobia, nausea, and vomiting. 14

Although the exact mechanism behind a migraine headache is not known, research over the last 15 years has lead to the idea that migraines are generated by a hyperexcitable brain. 12  This hyperexcitability mechanism is classically defined as coming from complex vascular distention and excessive pulsation of branches of the external carotid artery. 14  However, hyperexcitability of the brain may also come from a reduction of neuronal threshold. 8  Magnesium has an effect on smooth muscles, serotonin receptors, nitric oxide synthesis and release, as well as a variety of neurotransmitters, all of which when disrupted could possibly contribute to a migraine headache. 10

A difficult part in discovering a deficiency of magnesium in the brain is that serum levels may not be evident of the levels in other parts of the body.13  Cerebrospinal fluid and the brain are well buffered from a system change in magnesium levels, but it is hypothesized that, “a threshold may exist, where a sudden further decrease in systemic [magnesium] (e.g., during acute stress) superimposed on marginal systemic [magnesium] deficit could deplete brain [magnesium] levels.” 8  The effects of magnesium on migraine headaches can be investigated by reviewing studies that can better evaluate actual levels of magnesium and studies that show clinical evaluations of magnesium used as a treatment therapy.

Cortical Magnesium Levels
In this study the researchers evaluated the cortical levels of magnesium to investigate a pilot study that “suggested that disordered energy metabolism or Mg2+ deficiencies may be responsible for hyperexcitability of neuronal tissue in migraine patients.”8 The patients used in this study were patients that matched the criteria from Henry Ford Hospital in Detroit, MI.8  These patients were separated into a group that had migraines with aura, a group that had migraines without aura, a group that had hemiplegic migraines, and a group that were control subjects.8  Four areas of the brain were studied: posterior lower slice, anterior center slice, posterior center slice, and occipital cortex.8  Conclusions were made by comparing the results of the patients that suffered from migraines with the results of the control group.8

Upon comparison to the control group, it was seen that in patients with migraines without aura there was a trend toward an increase in magnesium levels in the posterior center slice. 8  However, in the patients with migraines with aura there was a trend toward decreased magnesium in the posterior lower slice.8  The patients with hemiplegic migraines showed the most pronounced change and had significantly lower magnesium levels in all posterior slices but not in the anterior regions. 8  It was also shown that with more severe neurologic symptoms there was a trend towards a decrease in magnesium in all posterior slices. 8

This study concludes that there is no substantial or consistent evidence to support abnormalities of energy metabolism in the patients, however, “it is hypothesized that disturbances in magnesium ion homeostasis may contribute to brain cortex hyperexcitability and pathogenesis of migraine syndromes associated with neurologic symptoms.” 8  It has been found in patients that suffer from migraines without aura, that there may be a compensatory change in magnesium levels that can counteract cortical excitability. 8

Serum Ionized Magnesium Levels in Menstrual Migraine
In this study, the researchers tested the hypothesis that magnesium deficiency may play an important role in menstrual migraine.9  Prior to the study, information was taken on 270 possible candidates.  Of these patients, 67 were selected that had migraines without aura and whose headaches were more common or got worse during menstruation.9  Serum was then taken from these women and evaluated for possible deficiencies in free ionized magnesium or total magnesium, and ionized calcium to ionized magnesium ratios.9

This study found that there was an ionized magnesium deficiency in 45% of the patients with menstrual migraine headaches, 15% of the patients with nonmenstrual migraine headaches, 14% during menstruation without a migraine headache, and 15% between menstruations and between migraine headaches. 9  It was also shown that the serum ionized calcium levels were within normal range but the ionized calcium to ionized magnesium levels were elevated in patients with menstrual migraine. 9  However, this study finds that only the measurement of ionized magnesium, and not ionized calcium, are needed in this type of experiment, but feel that the study should be confirmed.  The major finding of this study is that even though some women experience an ionized magnesium deficiency between migraines and menstruations, the combination of these two shows a higher incidence of deficiency. 9  This suggests that “[magnesium] may have a role in the development of the disease in this subgroup of patients.” 9

Oral Magnesium Load Test
In this study, the researchers investigated whether people that suffer from migraine headaches suffer from a systemic deficiency of magnesium.3  This experiment was preformed on 20 patients with migraines and 20 healthy volunteers.3  A baseline magnesium level was taken from serum and 24 hour urine specimens.3  All of the patients were given 3000mg of magnesium lactate orally during a 24 hour period and the magnesium levels were recorded again and compared to the baseline values.3

This study revealed that the baseline urine magnesium concentrations  tended to be lower in the migraine group than the baseline serum magnesium concentrations, but there was no statistically significant difference between the two. 3  In both the migraine group and the control group, the postload magnesium concentrations were significantly higher when compared with the baseline values. 3  However, even though the serum values did not differ, the 24 hour urinary magnesium excretions were significantly lower in the patients with migraines when compared to the control. 3  Therefore, this study shows that “magnesium retention occurs in patients with migraines after oral loading, suggesting s systemic magnesium deficiency.” 3

Oral Magnesium Oxide in the Treatment of Children with Migraines
In this study, researchers attempted to assess whether oral magnesium oxide reduces migraine frequency, severity, and associated features in children better than placebo.6  The children that were used were between the ages of 3 and 17 years old and had reported a four week history of moderate to severe weekly headaches that included a throbbing or pulsating quality, vomiting, anorexia, nausea, photophobia, sonophobia, or relief with sleep, but no fever, to rule out the possibility of associated infection.6  The subjects were randomly separated into groups that either received 9 mg/kg of body weight of magnesium oxide orally spread over three times per day or a placebo for sixteen weeks.6  The study was separated into eight, two week intervals and the number of days with at least one headache were recorded and compared between the treatment and placebo groups.6

The outcome of this study showed a “statistically significant downward trend in [headache] frequency over time in the [magnesium oxide] group but not in the placebo group,” however, “this study does not unequivocally determine whether oral [magnesium oxide] is or is not superior to placebo in preventing frequent migrainous [headaches] in children.” 6  This study also showed that the use of magnesium oxide was free of serious side effects compared to the placebo, but notes that larger trials with this therapeutic agent should be performed. 6

Intravenous Magnesium in the Treatment of Migraines during Pregnancy

In this study, the researchers assessed the efficacy of intravenous magnesium sulfate in the treatment of migraines during pregnancy.1  Ten pregnant women with migraine headaches were referred for this experiment from the obstetrics ward and the emergency room.1  These women all received intravenous hydration and one gram of magnesium sulfate in a 10% solution over a five minute period.1  The intensity of the headache was assessed on a scale from one to ten and compared between recordings before and after the infusion.1

The patients in this study reported significant reductions in pain after the infusion of magnesium sulfate and eight (80%) of the patients reported total pain relief.1  All of the patients, upon resolution of the headache, reported resolution of migraine associated nausea, photophobia, and phonophobia.1  However, minimal facial flushing and abdominal cramping occurred in two (20%) of the patients after receiving magnesium sulfate.1  The researchers of this study concluded that the intravenous use of magnesium sulfate may be a safe and effective treatment of migraines in with pregnancy, but a larger study will be helpful to corroborate these findings. 1

Treatment of Migraines with Magnesium in the Emergency Department

In this study the researchers attempted to determine the effectiveness of intravenous magnesium sulfate in the treatment of acute migraine attacks in the emergency department. 11  The patients that were used were all adults that presented to the Emergency Department with an acute migraine headache. 11  These patients were then infused with either 10 milligrams of intravenous metoclopramide, 2 milligrams of intravenous magnesium sulfate, or normal saline solution over a 10 minute period. 11  The patients were asked to rate their pain on a standard visual analogue scale at the beginning of the infusion, at 15 minutes, and at 30 minutes. 11  After 30 minutes the patients were asked if they were in need for rescue medication. 11  Along with this, the adverse effects felt by the patients were recorded and a follow up telephone call to ask about recurrence was placed 24 hours afterwards. 11

In all of the groups there was a more than a 25 millimeter improvement in the visual analogue score after thirty minutes, but no significant difference detected in the mean changes in the score. 11  The rate of recurrence after 24 hours was similar between all of the groups and the necessity of rescue medication was higher in the placebo group. 11  The researcher of this study concluded that, “Although patients receiving placebo required rescue medication more than the others, metoclopramide and magnesium have an analgesic effect similar to placebo in migraine attacks.” 11

Conclusions
A major shortcoming of many of these experiments was the small sample size.  Boska et. al. had 86 subjects, Mauskop et. al. had 61 subjects, Trauninger et. al. had 20 subjects, Wang et. al. had 118 subjects, and Wilson et. al. only had 10 subjects.  Upon further study of this subject, larger sample sizes would be recommended to more accurately assess the effects of magnesium on migraines.

Another limitation of the studies is that not all of the studies had the subjects separated into groups to differentiate migraine with aura and migraine without aura.  The results from the studies done by Boska et. al., Mauskop et. al., and Trauninger et. al. suggest that there is a notable difference between these groups and a separation of these patients into specific groups more accurate conclusions may be achieved.

After reviewing these studies, there seems to be evidence to suggest that there is a link between magnesium levels and migraine headaches.  The studies performed by Boska et. al., Mauskop et. al., and Trauninger et. al. showed that migraine sufferers had lower levels of magnesium in parts of their brains, lower serum ionized magnesium levels, and excreted a smaller amount of magnesium after a load test than an unaffected person.  This helps provide evidence to support the hypothesized role of a magnesium deficiency in the onset of migraine headaches.

The studies done by Wang et. al., Wilson et. al., and Cete et. al. demonstrated that magnesium can be used in the prophylaxis and acute onset of migraines in children, during pregnancy, and in the emergency department.  However, despite the fact that the findings of these studies do not prove to be conclusive on the effectiveness of the treatment, all show a marked improvement with very few side effects.  While magnesium is not yet proven to be a fail proof method for treating migraine headaches, there is evidence to suggest that it can be a natural alternative to safely and effectively provide relief from migraine headaches.

References 

1.    Wilson, M C, O’Brien, W F.  Intravenous Magnesium as a Treatment of Migraine in Pregnancy.  American Journal of Obstetrics and Gynecology.  2000; 182(1, Part 2):S154.
2.    Kelly, Anne-Maree.  Migraine: Pharmacotherapy in the Emergency Department.  Emergency Medical Journal.  2000; 17:241-245.  3.    Trauninger, Anita, Pfund, Zoltán, Koszegi, Tamás, Czopf, József.  Oral Magnesium Load Test in Patients with Migraine.  Headache.  2002; 42:114-119.
4.    Kaniecki, Robert.  Headache Assessment and Management.  JAMA.  2003; 298(No. 11):1430-1433.

5.    Snow, Vincenza, Weiss, Kevin, Wall, Eric M, Mottur-Pilson, Christel.  Pharmacologic Management of Acute Attacks of Migraine and Prevention of Migraine Headache.  Allas of Internal Medicine.  2002;137:840-849
6.    Wang, Fong, Van Den Eeden, Stephen K, Ackerson, Lynn M, Salk, Susan E, Reince, Robyn H, Elin, Ronald J.  Oral Magnesium Oxide Prophylaxis of Frequent Migrainous Headache in Children: A Randomized, Double-Blind, Placebo-Controlled Trial.  Headache.  2003; 43:601-610.
7.    Bigal, M E, Bordini, C A, Tepper, S J, Speciali, J G.  Intravenous Magnesium Sulphate in the Acute Treatment of Migraine without Aura and Migraine with Aura.  A Randomized, Double-Blind Placebo-Controlled Study.  Cephalalgia.  2002; 22:345-353.
8.    Boska, M D, Welch, K M A, Barker, P B, Nelson, J A, Schultz, L.  Contrasts in Cortical Magnesium, Phospholipid and Energy Metabolism between Migraine Syndromes.  Neurology.  2002; 58:1227-1233.
9.    Mauskop, Alexander, Altura, Bella T, Altura, Burton M.  Serum Ionized Magnesium Levels and Serum Ionized Calcium/Ionized Magnesium Ratios in Women with Menstrual Migraine.  Headache.  2002; 42:242-248.

10.             Maizels, Morris, Blumenfeld, Andrew, Burchette, Raoul.  A Combination of Riboflavin, Magnesium, and Feverfew for Migraine Prophylaxis: A Randomized Trial.  Headache.  2004; 44:885-890.

11.             Cete, Y, Dora, B, Ertan, C, Ozdemir, C, Oktay, C.  A Randomized Prospective Placebo-Controlled Study of Intravenous Magnesium Sulphate vs. Metoclopramide in the Management of Acute Migraine Attacks in the Emergency Department.  Cephalalgia.  2005; 25:199-204.

12.             Bigal, Marcelo E, Rapoprot, Alan M, Scheftell, Fred D, Tepper, Stewart J.  New Migraine Preventive Options: An Update with Pathophysiological Considerations.  Rev. Hosp. Clín. Fac. Med. S. Paulo.  2002; 57(6):293-298.

13.             Marz, Russell B.  Medical Nutrition from Marz 2nd Ed.  Portland, OR: Quiet Lion Press, 1998.

14.             Page, Clive, Curtis, Michael, Sutter, Morley, Walker, Michael, Hoffman, Brian.  Integrated Pharmacology 2nd Ed.  Edinburgh: Mosby, 2002.