Clinical Research: Improving Migraine Severity with Folic Acid and Pyridoxine
By Tori Hudson, ND
Author: Askari G, Nasiri M, Mozaffari-Khosravi M, et al.
Reference: The effects of folic acid and pyridoxine supplementation on characteristics of migraine attacks in migraine patients with aura: A double-blind, randomized placebo-controlled, clinical trial. Nutrition 2017;38:4-79.
Design: This was a parallel, double-blind, randomized placebo-controlled, clinical trial conducted in 95 patients with migraines/aura. Patients were randomly allocated to one of three groups of folic acid plus pyridoxine (n=34), folic acid alone (n=34) or placebo (n=34). Serum homocysteine levels were evaluated. Characteristics were determined including severity, frequency, duration, and duration per attack.
Patients in the folic acid plus pyridoxine group received 5 mg folic acid and 80 mg pyridoxine daily; the folic acid group only received 5 mg/day and the placebo group received lactose capsules. All patients received routine treatment for their migraines which they had previously been taking including; valproate, topiramate, propranolol. Patients were evaluated at baseline and at 3 months.
Participants: Patients were between the ages of 18 and 65 who had a history of migraines for at least 5 years and had a 1-year history of severe, recurrent and at least one attack per month, lasting 4 hours or more. Patients also had a current diagnosis of migraines with aura. Individuals were excluded if they were taking vitamin supplements or had clinical cardiovascular diseases, previous stroke, and chronic renal failure.
Of the 102 patients participating in the study, 3 in the folic acid group and 4 in the placebo group were excluded due to a change in medications or gastrointestinal disorders or personal reasons. A total of 95 individuals completed the study.
Patients were recruited from clinics of the Isfahan University of Medical Sciences, Isfahan, Iran. There was no mention of gender.
Primary outcome: Dietary intakes were the same in all three groups in areas of fruits, nuts, citrus, riboflavin, pyridoxine, folate, cobalamin, magnesium, sodium, saturated fatty acids, polyunsaturated fatty acids, linoleic acid, linolenic acid or the ratio of omega 6 to omega 3 fatty acids, in a 3 day dietary record.
Key findings: The folic acid combined with pyridoxine significantly decreased headache severity, the frequency of attacks and daily headache duration in those patients who had migraine with aura. Folic acid alone had no effect on these same characteristics when compared to placebo. However, even the folic acid combined with pyridoxine did not really have any effect on duration of the migraine attack after controlling for potential confounding factors.
Practice Implications: Migraine headaches are most prevalent in middle-aged men and women, and more common in women. There are two major classes of migraines: those with aura and those without. While the majority of symptoms are the same in both classes, about 25% of those with migraines have auras which include a transient disturbance in visual, sensory, language or motor function. Migraines can significantly affect quality of life and pharmacologic management can be expensive and fraught with side effects. Many non-pharmacologic therapies have shown some evidence including ginger, butterbur, vitamin D, riboflavin, magnesium, coenzyme Q 10 and relaxation training.
One thought about the mechanism of action is that folic acid and pyridoxine deficiencies may be present in migraine patients. It has also been shown that migraines, and especially migraines with auras are associated with point mutation in the MTHFR gene. It is thought that folic acid and pyridoxine can lessen migraine symptoms by affecting homocysteine levels. Folic acid and pyridoxine in high doses can reduce the effects of this mutation. While the research has been focused on folic acid, with this mutation in mind, one would think that a methylated folate would be a more optimal choice.