Targeting MTHFR for the treatment of migraines

ABSTRACT

Introduction: Migraine is a common neurovascular disorder classified by the World Health Organization as one of the most debilitating diseases. Migraine is a complex disease and is a consequence of an interaction between genetic, epigenetic and environmental factors. The MTHFR gene is one of the few replicated genetic risk factors for migraine and encodes an enzyme that is crucial for the folate and the methionine cycles. Individuals carrying the T allele of the MTHFR C677T polymorphism have increased plasma concentrations of homocysteine which leads to endothelial cell injury and alterations in coagulant properties of blood.

Areas covered: This review focuses on the recent advances in genetics and the role of the MTHFR gene and homocysteine metabolism in migraine etiopathogenesis. The article summarizes the potential of targeting MTHFR and homocysteine for disease prevention.

Expert opinion: Determination of MTHFR C677T polymorphisms as well as measurement of homocysteine concentrations may be useful to migraine patients, particularly those suffering from migraine with aura. Preliminary studies support the use of folate, vitamin B6 and vitamin B12 for the prevention of migraine. However, the results of these studies await replication in larger randomized controlled clinical trials.

KEYWORDS:

• MTHFR
• migraine
• homocysteine
• folic acid
• vitamin B16
• vitamin B12

Article Highlights

• Migraine is one of the most disabling diseases in developed countries.

• The etiology of the disease is related to a complex interplay between several genetic and environmental risk factors.

• The MTHFR gene is the most investigated genetic risk factors in migraine and has mainly been associated with migraine with aura phenotype.

• The carriage of the T allele of the MTHFR C677T polymorphism is significantly associated with migraine with aura as well as with increased homocysteine concentrations and a more severe disease phenotype.

• Preliminary studies showed that vitamin supplementation (folate, vitamin B6 and vitamin B12), decreasing homocysteine concentrations, may reduce the frequency of headache as well as disability in migraineurs.

• Large randomized controlled studies are needed to confirm the effects of vitamin supplementation in migraine with aura prophylaxis.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was fully supported by 2016 and 2017 research grants from the Ministero dell’Università e della Ricerca Scientifica (MIUR) of Italy.