Fifty-two patients with migraines accompanied by an aura were randomly assigned to receive, in double-blind fashion, daily B vitamins (2 mg of folic acid, 25 mg of vitamin B6, and 400 mcg of vitamin B12) or placebo for six months. The mean plasma homocysteine concentration, which was elevated at 10.8 mcmol/L at baseline, decreased by 39% in the active-treatment group (p=0.001 compared with the change in the placebo group). The proportion of patients suffering from severe migraine disability fell from 61% to 30% in the active-treatment group (p=0.01) and from 54% to 47% in the placebo group (not significant). Median headache frequency fell by 75% in the active-treatment group (p=0.04), but did not change in the placebo group. Median pain severity decreased by 25% in the active-treatment group (p=0.002), but did not change in the placebo group. The reduction in migraine disability was restricted primarily to the 31 patients with the CC and CT C677T genotypes of 5,10-methyllenetetrahydrofolate reductase (MTHFR). In that subgroup, the proportion of patients suffering from severe migraine disability fell from 76% to 28% (p=0.002). In contrast, no significant reduction in severe migraine disability was seen in patients with the TT genotype. The authors of this report suggested that patients with the TT genotype may have needed a higher dose of folic acid, since patients with that genotype have an increased folate requirement.
Comment from Alan Gaby, MD
This is the second study to demonstrate that homocysteine-lowering regimes decrease the frequency and/or severity of migraines in chronic migraine sufferers who have elevated or borderline-high homocysteine levels. Measurement of plasma homocysteine should therefore be considered for patients with recurrent migraines, and patients found to have hyperhomocysteinemia should be treated accordingly. The mechanism by which homocysteine might trigger migraines is not clear.
One may also look at using natural forms of folate, rather than synthetic folic acid.
Lea RA, et. al. The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. Pharmacogenet Genomics. 2009;19:422-428.
Reprinted with exclusive permission of Townsend Letter for Doctors and Patients January 2010