Nutrients for migraine prevention

 

By Alan R. Gaby, M.D.

More than 10% of Americans suffer from migraines. Even the most effective medications prescribed for migraine prophylaxis reduce migraine frequency by no more than 50%, and many of these drugs are associated with significant side effects. Safer and more effective ways of preventing and treating migraines are therefore needed.

Mitochondrial energy production appears to be impaired in people with recurrent migraines, and this impairment might play a role in the pathogenesis of migraines. Nutrients that are involved in energy production might therefore be beneficial. Magnesium is a cofactor for the synthesis of adenosine triphosphate (ATP), the body's main storage form of energy. Riboflavin (in the form of flavin adenine dinucleotide [FAD]) and coenzyme Q10 are cofactors in the electron-transport chain, a biochemical cascade that culminates in ATP synthesis. Each of these three nutrients has been shown in clinical trials to decrease the recurrence rate of migraines.

Magnesium
Eighty-one migraine sufferers were randomly assigned to receive, in double-blind fashion, 600 mg per day of magnesium or placebo for 12 weeks. During the last four weeks of the study, as compared with baseline, the mean frequency of migraines was reduced by 42% in the magnesium group and by 16% in the placebo group (p < 0.04 for the difference in the change between groups). Adverse effects of magnesium were diarrhea in 18.6% of patients and gastric irritation in 4.7%.¹ In other research, effective migraine prophylaxis was achieved with a magnesium dose of 360 mg per day,² which is less likely than the higher dose to produce gastrointestinal side effects.

Riboflavin
Fifty-five migraine patients were randomly assigned to receive, in double-blind fashion, 400 mg of riboflavin once a day or placebo for three months. In intent-to-treat analysis, riboflavin was superior to placebo in reducing attack frequency (p = 0.005) and number of headache days (p = 0.012). The proportion of patients who experienced at least a 50% reduction in the number of headache days was 59% for riboflavin and 15% for placebo (p = 0.002). Three minor adverse events occurred, two in the riboflavin group (diarrhea and polyuria) and one in the placebo group.³

The dose of riboflavin used in this study was about 400 times as much as the amount present in a typical diet. Uncontrolled trials from the 1940s and 1950s suggest that lower doses of riboflavin (such as 5-10 mg three times per day) can also prevent migraine recurrences. While high-dose riboflavin has not been associated with significant toxicity in short-term studies, it has the potential to act as a photo-sensitizer or to cause imbalances of other nutrients. Therefore, it would seem prudent to reserve high-dose riboflavin for patients who do not respond to moderate doses.

Coenzyme Q10
Forty-two migraine patients were randomly assigned to receive, in double-blind fashion, 100 mg of coenzyme Q10 three times per day or placebo for four months. The proportion of patients who had a 50%-or-greater reduction in attack frequency during the fourth month compared with baseline was 48% in the coenzyme Q10 group and 14% in the placebo group (p = 0.02). The mean reduction in attack frequency was 27% in the coenzyme Q10 group and 2% in the placebo group (p < 0.05 for the difference in the change between groups).⁴

B vitamins, homocysteine, and migraines
Polymorphisms of the 5,10-methylenetetrahydrofolate reductase gene (mainly homozygosity for 677C → T) that are associated with reduced enzyme activity and moderate hyperhomocysteinemia have been found to be common in migraine patients. In one study, 16 of 22 children with recurrent migraines without aura had one of these polymorphisms. In those children, supplementation with 5 mg per day of folic acid (which is known to lower homocysteine levels) resulted in a complete cessation of migraine attacks in 10 of 16 children and substantial improvement in each of the others. Plasma homocysteine levels became normal in all 16 patients.⁵ While it was not clear whether elevated homocysteine per se was the cause of the migraines, another study also found that treatment with homocysteine-lowering nutrients (folic acid, vitamin B₆, and vitamin B₁₂) markedly reduced headache frequency in patients with elevated homocysteine levels.⁶ Based on these observations, it would seem worthwhile to measure plasma homocysteine levels in migraine patients and to recommend B-vitamin supplementation for those with elevated levels.

Other treatments
Other treatments that have been found to be effective for preventing migraines include identification and avoidance of allergenic foods, quitting smoking, stopping the use of oral contraceptives, and administration of certain herbal remedies (i.e., feverfew and butterbur).

Alan R. Gaby, MD, received his B.A. from Yale University, his M.S. in biochemistry from Emory University, and his M.D. from the University of Maryland. He is past president of the American Holistic Medical Association and Contributing Medical Editor of The Townsend Letter for Doctors and Patients. He provided expert testimony to the White House Commission on Complementary and Alternative Medicine regarding the cost-effectiveness of nutritional supplements. He is the author of Preventing and Reversing Osteoporosis and B6: The Natural Healer, andco-author of The Patient's Book of Natural Healing. He has compiled a collection of more than 25,000 scientific papers related to the field of nutritional medicine. He has appeared on the CBS Evening News and the Donahue Show.

REFERENCES

1. Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 1996;16:257-263.
2. Facchinetti F, Sances G, Borella P, Gonazzani AR, Nappi G. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache 1991;31:298-304.
3. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998;50:466-470.
4. Sandor PS, Di Clemente L, Coppola G, Saenger U, Fumal A, Magis D, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology 2005;64:713-715.
5. Di Rosa G, Attina S, Spano M, Ingegneri G, Sgro DL, Pustorino G, et al. Efficacy of folic acid in children with migraine, hyperhomocysteinemia and MTHFR polymorphisms. Headache 2007;47:1342-1344.
6. Lea R, Colson N, Quinlan S, Macmillan J, Griffiths L. The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. Pharmacogenet Genomics 2009;19:422-428.