The most widely used are butterbur, riboflavin, CoQ10, magnesium and melatonin.

Riboflavin helps the mitochondrial energy system, which is needed for cell survival, and this is found to be reduced in migraine. It is also called vitamin B2. Most studies used 400 mg a day. The American Academy of Neurology has concluded that it is probably effective for the preventative treatment of migraine in adults though not recommended for use in children. Possible side effects are diarrhea and increased frequency of urination as well as bright yellow urine.

Coenzyme Q10 is also important in mitochondrial energy. The usual dose is 100 mg 3 times a day for a 3-month trial. Results of studies are mixed. The medication is considered possibly effective.

Magnesium has been found to be low in patients with migraine. A deficiency of this increases glutamate, a transmitter that causes hyperexcitability in neurons, and migraine patients have increased hyperexcitability in their brains. Studies show conflicting results. Recommended dose is 400 to 600 mg a day for at least 3 months. Possible side effects are diarrhea and flushing.

Butterbur is made from a shrub called Petasites. It inhibits calcium channels, which is its probable mechanism of action in migraine. It was patented in Germany in 1988. It seems helpful for adults and children, with the adult dose 150 mg a day for a 3-month trial as a preventative. It was previously considered safe, with burping being the only side effect. However, there are recent reports of liver damage. In the UK, 9 cases were reported of acute hepatitis, and 2 of the 9 cases resulted in liver failure, requiring liver transplantation. Children and pregnant women should certainly not take butterbur. Adults can do so if they are aware of the risks and liver function blood tests are monitored.

Feverfew is derived from a chrysanthemum. Its mechanism of action is unknown. It may be effective. Long-term safety data are lacking, though it appears well tolerated.

Melatonin is widely available over-the-counter, often used for insomnia, and has been tested extensively as a preventative for cluster headache and to some degree for migraine. Most studies have shown negative results.

The take-home message is that butterbur should not be used, that melatonin is not effective, that other nutraceuticals may or may not be effective but seem safe. A combination product is available over-the-counter, containing feverfew 100 mg, magnesium 300 mg, and riboflavin 400 mg and may be a reasonable choice. Another product is sublingual (under the tongue) and contains feverfew and ginger. This seemed effective in small trials.

Behavioral approaches are a safe and probably equally or more effective alternative to nutraceuticals. They include relaxation training, thermal biofeedback, EMG biofeedback, and especially cognitive behavioral therapy. They have been shown to reduce pain catastrophizing, increase the number of positive coping strategies, and reduce migraine-related disability. They are especially appropriate in women who are planning pregnancy or who are pregnant or breastfeeding. Aerobic exercise combined with behavioral management may improve outcomes.

Jack Florin, MD

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