Migraine is a complex condition that may in part be related by endothelial and cerebrovascular disruption [13]. Some studies showed that supplementation of B vitamins lowered homocysteine levels and reduced the occurrence of migraine in women [14]. Besides, polymorphisms in genes coding for key player enzymes in the folate metabolic pathway have been investigated in order to define a relation with the pathology and its treatment. The C677T variant in the methylenetetrahydrofolate reductase (MTHFR) has been associated with increased risk of migraine with aura [15,16]. The C allele carrier is also related to higher reduction in homocysteine levels, severity of pain in migraine and percentage of high migraine disability in patient supplemented with B vitamins [14]. The same approach has been adopted for the polymorphism A66G in methionine synthase reductase gene (MTRR): the A allele carriers showed a better response to B vitamin administration [14]. Roecklein et al. [17] performed a haplotype analysis of migraine risk and MTHFR, MTRR and methionine synthase (MTR), including subjects with non-migraine headache (N = 367), migraine without aura (N = 85), migraine with aura (N = 167), and no headache (N = 1347). Haplotype analysis suggested an association between MTRR haplotypes and reduced risk of migraine with aura.