Abstract text (incl. figure legends and references)

Question: Migraine is a common, painful, and debilitating disease. Previous studies have shown that B vitamins especially vitamin B2 are beneficial in treating pain and migraine; however, the mechanism of their actions, and also the effects of other vitamin B supplements remain unclear. The purpose of the present study was to examine the effects of vitamin B1, B6, B12 supplementation versus placebo on serum levels of CGRP, endothelial nitric-oxide synthase, homocysteine and headache characteristics in women with episodic migraine (EM).

Methods: This double-blind, placebo-controlled, randomized clinical trial study included 80 episodic migraineurs who randomly assigned into four equal groups to receive either daily dose of vitamin B6 (80 mg), B12 (500 μg), B1 (300 mg) or placebo for 12 weeks. At baseline and after the trial, general characteristics, biochemical factors, anthropometric measurements, dietary intake, physical activity and headache diaries form were collected. CGRP, eNOS, and homocysteine levels were measured using an ELISA kit before and after the intervention.

Results: 64 patients completed the study. After controlling baseline values and confounders supplementation with vitamin B6 reduced serum levels of CGRP compared to placebo (P <0.047) and B12 groups (P <0.008). Each of the B1, B12 and B6 supplements resulted in a decrease in the mean severity of headache attacks compared to the placebo group (P<0.001, P<0.006, P<0.001). The number of headache days went down significantly in only groups B1 and B12 (P<0.022, P<0.004). In contrast, the duration of headache attacks did not differ significantly among the groups.

Conclusion: We found that supplementation with vitamins B1, B12, and B6 improved migraine characteristics. The effect of vitamin B6 at least partly seems to be due to decreasing serum levels of CGRP in patients with episodic migraine. Further research is needed to determine the mechanisms of action of other vitamins on migraine.