Targeting MTHFR for the treatment of migraines

Expert Opin Ther Targets. 2019 Jan;23(1):29-37. doi: 10.1080/14728222.2019.1549544. Epub 2018 Nov 28.


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; folic acid; homocysteine; migraine; vitamin B12; vitamin B16.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Folic Acid / administration & dosage
  • Genetic Predisposition to Disease
  • Homocysteine / blood
  • Homocysteine / metabolism
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Migraine Disorders / genetics
  • Migraine Disorders / physiopathology
  • Migraine Disorders / therapy*
  • Molecular Targeted Therapy*
  • Polymorphism, Genetic
  • Vitamin B 12 / administration & dosage
  • Vitamin B 6 / administration & dosage


  • Homocysteine
  • Vitamin B 6
  • Folic Acid
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Vitamin B 12