Epilepsy and B Vitamins

Folate deficiency is most likely to occur in patients on long-lasting AED therapy. Furthermore, folate concentrations are inversely related to the number of prescribed AEDs. Patients on combinations of two or more AEDs tend to have lower folate levels than patients on monotherapy. Combinations of AEDs may have synergistic effects on folate absorption and/or metabolism. Moreover, the dietary intake of B vitamins tends to decrease with an increasing number of AEDs. Patients on combination therapy tend to a have more severe epilepsy, often associated with other neurological deficits and may even need to live in institutions. 

It appears reasonable to recommend supplementation with several B vitamins in physiological doses to many patients with epilepsy. Patients on inducer AEDs and VPA, and patients with an insufficient diet, are at risk for deficiency of several B vitamins. Moreover, the evidence that folic acid can prevent adverse effects in patients on AEDs is not much higher than the evidence for a protective effect of vitamins B2, Bg, B7 and B12 (Ranganathan and Ramar-atnam 2005). In animal studies, deficiency of vitamins B2 and Bg has been related to the occurrence of foetal malformations. Therefore, women of childbearing potential should supplement their diet with vitamin B2 and Bg, as well as folic acid. 

This chapter describes how some rare B vitamin disorders may cause brain dysfunctions with seizures and how the treatment of epilepsy with antiepileptic drugs may cause B vitamin disturbances. 

Folate supplements will rectify the megaloblastic anemia of vitamin Bj2 deficiency but may hasten the development of the (irreversible) nerve damage found in B,2 deficiency. There is also antagonism between fohc acid and the anticonvulsants used in the treatment of epilepsy. 

Folic acid is safe, even at levels of daily oral supplementation up to 5—10 mg (97). Gastrointestinal upset and an altered sleep pattern have been reported at 15 mg/day (98). A high intake of folic acid can mask the clinical signs of pernicious anemia which results from vitamin B 2 deficiency and recurrence of epilepsy in epileptics treated with dmgs with antifolate activity (99). The acute toxicity (LD q) is approximately 500 and 600 mg per kg body weight for rats and mice, respectively (100). 

Recurrent seizures in two patients with well-con-trolled epilepsy were associated with use of "Ginkgo biloba," presumably consisting of leaf extracts, for 12 days to two weeks (Granger 2001). A review of gingko hypothesized that the compound ginkgotoxin (4 -0-methylpyridoxine) may be responsible for lowering seizure threshold by inhibiting synthesis of vitamin B (Leistner and Drewke 2010). 

Nettekoven S, Strohle A, Trunz B, Wolters M, Hoffmann S, Horn R, Steinert M, Brabant G, Lichtinghagen R, Welkoborsky HJ, Tuxhorn I, Hahn A. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy. Eur J Pediatr 2008 167(12) 1369-77. 

---