A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial

Headache. 2004 Oct;44(9):885-90. doi: 10.1111/j.1526-4610.2004.04170.x.


Objective: To determine the efficacy for migraine prophylaxis of a compound containing a combination of riboflavin, magnesium, and feverfew.

Background: Previous studies of magnesium and feverfew for migraine prophylaxis have found conflicting results, and there has been only a single placebo-controlled trial of riboflavin.

Design/methods: Randomized double-blind placebo-controlled trial of a compound providing a daily dose of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo contained 25 mg riboflavin. The study included a 1-month run-in phase and 3-month trial. The protocol allowed for 120 patients to be randomized, with a preplanned interim analysis of the data after 48 patients had completed the trial.

Results: Forty-nine patients completed the 3-month trial. For the primary outcome measure, a 50% or greater reduction in migraines, there was no difference between active and "placebo" groups, achieved by 10 (42%) and 11 (44%), respectively (P=.87). Similarly, there was no significant difference in secondary outcome measures, for active versus placebo groups, respectively: 50% or greater reduction in migraine days (33% and 40%, P=.63); or change in mean number of migraines, migraine days, migraine index, or triptan doses. Compared to baseline, however, both groups showed a significant reduction in number of migraines, migraine days, and migraine index. This effect exceeds that reported for placebo agents in previous migraine trials.

Conclusion: Riboflavin 25 mg showed an effect comparable to a combination of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo response exceeds that reported for any other placebo in trials of migraine prophylaxis, and suggests that riboflavin 25 mg may be an active comparator. There is at present conflicting scientific evidence with regard to the efficacy of these compounds for migraine prophylaxis.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Magnesium / therapeutic use*
  • Male
  • Migraine Disorders / prevention & control*
  • Phytotherapy*
  • Plant Preparations / therapeutic use*
  • Riboflavin / therapeutic use*
  • Tanacetum parthenium*
  • Treatment Outcome


  • Drug Combinations
  • Plant Preparations
  • Magnesium
  • Riboflavin