September 2020
Jeanette A. Maier, Gisele Pickering, Elena Giacomoni,3Alessandra Cazzaniga,1and Paolo Pellegrino

 

Abstract

Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines.

A number of double-blind randomized placebo-controlled trials have shown that magnesium is efficacious in relieving headaches and have led to the recommendation of oral magnesium for headache relief in several national and international guidelines.

Among several magnesium salts available to treat magnesium deficiency, magnesium pidolate may have high bioavailability and good penetration at the intracellular level.

Here, we discuss the cellular and molecular effects of magnesium deficiency in the brain and the clinical evidence supporting the use of magnesium for the treatment of headaches and migraines.

Keywords: magnesium, pidolate, deficiency, headache, migraine, BBB

 

Conclusions

Taken together, these results confirm a correlation between magnesium deficiency and headaches. In addition, they suggest magnesium deficiency could be an independent risk factor for migraine occurrence. Some of the trials presented in this review date from the 1990s; however, it is encouraging to see a revitalization of this subject with more recent systematic reviews and clinical trials.

Magnesium deficiency is more often present in postmenopausal women with osteoporosis (84%) [99] and in women aged 18 to 22 (20%) [100]. The use of magnesium with its relatively low side effects is particularly pertinent for these populations who are also particularly susceptible to the side effects of traditional drugs.

When assessing the efficacy of magnesium salt, variations in dosage, study design, methods of assessment and study population, all need to be evaluated, which can make it difficult to interpret which salt is preferable for treating headache. In terms of magnesium pidolate, it may have a lower capacity to enter bone cells, the body’s main deposit for magnesium [82], and may cause more magnesium to cross the BBB compared with other salts [95]. Due to its potential high bioavailability, it may have special relevance for the treatment of neurological conditions with a known connection to magnesium deficiency, such as headache. Based on the information in the literature, there is an argument for the use of magnesium pidolate in Italy. However, it needs to be borne in mind that only a limited number of studies have shown the benefits of magnesium pidolate in headaches, and further controlled studies are needed. This is particularly important with regard to elucidating any side effects, as the 1500–4500 mg dose is high compared to the other salts, which range between 242 mg and 600 mg.

Overall, the use of oral magnesium salt represents a well-tolerated and inexpensive addition for the treatment of headache patients, to reduce the frequency of attacks and the costs of treatment both in terms of economic burden and adverse events.