Folate, vitamin B12, and serum homocysteine levels in patients with chronic migraine and medication-overuse headache

Folate and vitamin B12 deficiency have been associated with neurological and neuropsyhiatric disorders. Moreover, the coenzymes formed from folic acid are instrumental in the conversion of homocysteine to methionine and this reaction requires vitamin B12 as a cofactor. Hyperhomocysteinemia is an independent risk factor for vascular diseases, such as heart disease and stroke. Objective: To examine folate, vitamin B12 and serum homocysteine levels in patients with chronic migraine and medication-overuse headache, compared to migraine patients. Methods: We analysed serum vitamins levels in 170 patients with chronic migraine and medication-overuse headache (MOH) (mean age 54 years) and in 50 patients suffering from migraine without aura (mean age 43 years). Homocysteine serum levels were available only for 118 MOH patients (mean age 52 years). Diagnosis were made according to ICHD-II criteria. All patients have been referred to the Headache Centre of Modena University Hospital. Venous blood samples were drawn in the morning, after an overnight fast. Serum vitamins and homocysteine levels were measured by immunometric techniques (folate: ion capture immuno assay, ICIA; vitamin B12: microparticles enzyme immuno assay, MEIA; homocysteine: fluorescence polarized immuno assay) at our laboratory. Results: Folate levels below the reference range (4-20 ng/ml) were found significantly more frequently in MOH patients (27%) than in migraine patients (12%) (P <0.05, Chi-square test). A similar proportion of patients of the two groups had vitamin B12 lower than the references values (200-900 pg/ml). Homocysteinemia higher than the reference range (<20 umol/l for subjects over 60 years; <13 umol/l for subjects below 60 years) was found significantly more frequently in MOH patients (15%) than in migraine patients (2%) (P <0.05, Chi-square test). Conclusions: The low folate and high homocysteine levels that we detected in many MOH patients could contribute to the numerous medical and psychiatric comorbidities which have been reported in patients suffering from this disorder. Our results suggest that the assessment of folate, and homocysteine levels should be considered in MOH patients since folate supplement could help to improve their complex condition.