"Natural" or Alternative Medications for Migraine Prevention

Randolph W. Evans, MD; Frederick R. Taylor, MD


Headache. 2006;46(6):1012-1018. 

In This Article


Riboflavin (vitamin B2) is a water-soluble essential precursor to flavin mononucleotides necessary for electron transport within the Krebs cycle. It is essential to normal production of ATP and thus for maintaining membrane stability and for all energy-related cellular functions. RCTs involving riboflavin are extremely scarce, with no dose-ranging study involving riboflavin alone and no definite proof of efficacy (Grade B evidence, which also includes several favorable nonrandomized open-label studies).

RCTs are limited to 2 trials, 1 of which used a combination agent. In the only RCT involving riboflavin alone, Schoenen et al studied 55 patients and reported that 59% of the subjects receiving riboflavin 400 mg/day for 3 months experienced a ≥50% reduction in migraine attacks compared with 15% for placebo.[40] Statistically significant reductions in both migraine frequency and number of headache days were reported. In the only other migraine RCT of riboflavin, Maizels et al studied 49 subjects taking 25 mg "placebo" riboflavin (to color the urine) or combination of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg for 3 months.[41] The number of migraine attacks, number of migraine days, and migraine index were lower in both groups as compared to baseline, but not statistically significant between the 2 for any endpoint. Interestingly, the "placebo" 25 mg dose produced ≥50% reduction in the number of migraine attacks in 42%, while the combination formulation in 44%. One interpretation is that perhaps 25 mg riboflavin is an active treatment, and the other that this is a failed trial.[8] In any case, the trials were small, and to settle the issue larger RCTs (with dose-ranging integral to the design) are required.

Adverse events reported from the studies investigating riboflavin have been limited to diarrhea and polyuria, both occurring in extremely low numbers. There is no known long-term toxicity or anticipated from supplementation provided to nonpregnant individuals; while apparently nontoxic at any dose in adults, and while fetal toxicity is unproven, riboflavin supplementation in pregnancy cannot currently be recommended. Patients should be warned against obtaining 400 mg/day from a multivitamin due to the potential for significant overdose of several toxic vitamins. They also should be advised that riboflavin will produce florescent yellow urine.


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