Can Magnesium be Considered a Therapeutic Option in Migraine?

A recent research shows that patients with migraine have relatively low levels of serum Magnesium (Mg) compared to healthy controls, and there is an inverse relation between serum Mg levels and the frequency of migraine attacks, suggesting that Mg is significantly involved in mechanisms underlying migraine pathogenesis and can be explored as a therapeutic option.

Migraine is one of the primary headaches that is considered to be a neurovascular disorder. With an estimated global prevalence of 15%, migraine leads to an enormous loss of productive life years. The hyperexcitability of the cerebral cortex has been recognized as an important factor in the pathogenesis of migraine, which leads to a cascade of cortical spreading depression, vascular dysfunction and sterile neurogenic inflammation. There is a longstanding quest for the search of physiological forces that have either direct or indirect involvement in the described mechanisms of pathophysiology of migraine so that new targets for antimigraine therapies could be identified since the existing therapies have proven to be insufficient in a substantial proportion of migraine patients.

Magnesium concentration affects N-Methyl D-Aspartate (NMDA) receptors, serotonin receptors, and other migraine-related receptors and neurotransmitters, thereby regulating neuronal excitability. Due to these effects, Mg has attracted attention regarding its role in the pathophysiology of migraine and as a potential therapeutic agent.

Mahajan et al conducted a prospective observational study to evaluate the serum levels of Mg in patients of migraine during the attack and in-between attacks as compared to healthy controls. A total of 50 migraine patients who fulfilled inclusion criteria were enrolled in the study.

They elicited the patients' history of migraine, taking note of the age of onset, duration of disease, frequency of migraineous attacks each month and the average duration of those attacks. Headache characteristics such as triggering factors, aura and its type, location, nature, severity, onset to peak latency and accompanying symptoms were noted. After obtaining other relevant history regarding any comorbidities and smoking habits, study participants – who included both migraine cases and healthy controls – underwent general, physical and neurological examination. Blood samples of migraineurs were taken in the morning after fasting for a minimum of 8 hours, once during their headache attack (or within 24 hours after headache) and then at least 7 days after their last migrainous headache (interictal phase). Blood samples of controls were taken in the morning after a minimum of 8 hours of the fasting period. Estimation of serum Mg levels was done in the biochemistry laboratory by colorimetric tests.

They found that the mean serum Mg levels in migraine cases were lower than those in healthy controls during the interictal phase. It was also observed that mean serum Mg levels during headache attacks were lower than in the interictal phase. There was no significant difference in serum levels of Mg with age, sex, BMI, duration of disease, and the presence or absence of aura, but mean serum Mg levels in migraine cases with frequency ≥4/month was

significantly lower than migraine cases with frequency <4/month. There was a negative linear relationship between serum Mg and frequency of attacks in migraine cases.

Pharmacological approaches that are available today for migraines are effective in only a limited number of patients and there is a need for better approaches. The role of Mg in defining the threshold for migraine attacks and its involvement in the pathophysiologic mechanisms of migraine has become evident recently that makes it a potential therapeutic agent in migraine.

Reference: Mahajan R, Anand KS, Mahajan RK, Garg J, Juneja A. Serum Magnesium Levels During the Ictal and Interictal Phase in Patients of Migraine: A Prospective Observational Study. Neurol India 2022;70:1852-5