Clinical Briefs

With Comments from John La Puma, MD, FACP

Riboflavin for Migraine Prophylaxis

November 1998; Volume 1: 131-132

Source: Schoenen J, et al. Effectiveness of high-dose riboflavin in migraine prophylaxis: A randomized controlled trial. Neurology 1998;50:466-470.

A deficit of mitochondrial energy metabolism may play a role in migraine pathogenesis. We found in a previous open study that high-dose riboflavin was effective in migraine prophylaxis. We now compared riboflavin (400 mg daily) and placebo in 55 patients with migraine in a randomized trial of three months duration. Using an intention to treat analysis, riboflavin was superior to placebo in reducing attack frequency (P = 0.005) and headache days (P = 0.012). The proportion of patients who improved by at least 50%, i.e., "responders," was 15% for placebo and 59% for riboflavin (P = 0.002) and the number-needed-to-treat for effectiveness was 2.3. Three minor adverse effects occurred—two in the riboflavin group (diarrhea and polyuria) and two in the placebo group (abdominal cramps). None was serious. Because of its high efficacy, excellent tolerability, and low cost, riboflavin is an interesting option for migraine prophylaxis and a candidate for a comparative trial with an established prophylactic drug.


In a rigorous, impressive, multicenter study funded by the Belgian Migraine Society, European investigators tried 400 mg of once daily oral riboflavin (vitamin B2) on patients with migraines, with or without aura who had between two and eight attacks monthly, had no more than five days of interval headaches, no analgesic overconsumption and no serious organic or psychiatric disease. Women were required to have adequate contraceptive protection.

After three months, riboflavin dramatically reduced headache frequency and number of headache days but not headache intensity. Riboflavin did, however, take the full three months to have a significant effect.

Why should riboflavin work in helping to prevent migraine? Vitamin B2 is a component of two co-enzymes and a precursor to the flavoenzymes that are involved in mitochondrial energy production in the brain. The vitamin may help patients reduce migraine attack frequency by increasing mitochondrial energy metabolism and with it, the intracerebral threshold for attacks.

The RDA (soon to be RDI) for riboflavin is 1.3-1.7 mg. Common food sources are organ meats, other meats, milk, eggs, and green vegetables. Grains, cereals, and flours are often fortified with riboflavin. For migraine prophylaxis, however, patients are better off with a supplement than with food; here, the vitamin functions as a medication, and without apparent side effect.


Consider recommending a three-month trial of riboflavin prophylaxis to patients who have two or more mi-graines monthly, and who want to avoid using beta blockers, valproate, and other prophylactic medications.