The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability

Background Migraine is a prevalent and debilitating disease that may, in part arise because of disruption in neurovascular endothelia caused by elevated homocysteine. This study examined the homocysteine-lowering effects of vitamin supplementation on migraine disability, frequency and severity and whether MTHFRC677T genotype influenced treatment response. Methods This was a randomized, double-blind placebo, controlled trial of 6 months of daily vitamin supplementation (i.e. 2 mg of folic acid, 25 mg vitamin 136, and 400 mu g of vitamin B-12) in 52 patients diagnosed with migraine with aura. Findings Vitamin supplementation reduced homocysteine by 39% (approximately 4 mu mol/1) compared with baseline, a reduction that was greater then placebo (P=0.001). Vitamin supplementation also reduced the prevalence of migraine disability from 60% at baseline to 30% after 6 months (P=0.01), whereas no reduction was observed for the placebo group (P>0.1). Headache frequency and pain severity were also reduced (P<0.05), whereas there was no reduction in the placebo group (P>0.1). In this patient group the treatment effect on both homocysteine levels and migraine disability was associated with MTHFRC677T genotype whereby carriers of the C allele experienced a greater response compared with TT genotypes (P<0.05). Interpretation This study provides some early evidence that lowering homocysteine through vitamin supplementation reduces migraine disability in a subgroup of patients. Larger trials are now warranted to establish whether vitamin therapy is a safe, inexpensive and effective prophylactic option for treatment of migraine and whether efficacy is dependant on MTHFRC677T genotype. Pharmacogenetics and Genomics 19:422-428 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.