Forty-nine patients with migraines were randomly assigned to receive, in double-blind fashion, daily treatment with 1) a combination of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg, or 2) "placebo" (riboflavin 25 mg) for 3 months. The proportion of patients achieving a 50% or greater reduction in migraine frequency (the primary outcome measure) was 42% in the combination group and 44% in the low-dose-riboflavin group (p = 0.87). Both treatments reduced the frequency of migraines by approximately one-third, and decreased the number of migraine days by about one-fourth. In addition, mean headache severity (p = 0.04) and the number of days with tension headache decreased (p = 0.01) in the low-dose-riboflavin group, but not in the group receiving combination therapy. The effect of low-dose riboflavin was greater than that reported for placebo in previous migraine trials.

Comment: Previous studies have demonstrated impaired mitochondrial energy production in brain tissue of patients with recurrent migraines. Riboflavin, as a component of flavin adenine dinucleotide (FAD), has the capacity to enhance energy production, through its participation in the electron transport chain. In open and placebo-controlled studies, a dose of 400 mg/day of riboflavin was effective for preventing migraine recurrences. That dose, which is at least 200 times the amount present in a typical diet, was presumably chosen to give the treatment the best chance of working. While riboflavin does not appear to cause significant adverse effects even at high doses, taking large amounts of any single nutrient might cause subtle imbalances in body chemistry. For that reason, if lower doses were found to be equally effective, they would be preferable to the higher amounts used in earlier studies.

Although there was no true placebo group in the current study, the results suggest that a relatively low dose of riboflavin can prevent migraines. The combination treatment used in this study consisted of three compounds that have each been shown, when given alone, to reduce the incidence of migraines. While it is somewhat surprising that low-dose riboflavin was at least as effective as this combination treatment, it is possible that one or more of the substances in the combination product interfered with the effect of the others, or that massive doses of riboflavin are less effective than more moderate doses.

Maizels M, et al. A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial. Headache 2004;44:885-890.