Vitamin-B12-Metabolismus unter Anfallssuppressiva bei Menschen mit Epilepsie

In previous studies, increasing evidence has emerged suggesting that antiseizure medication (ASMs) may have an impact on vitamin B12 metabolism particularly on vitamin B12 itself, folic acid, and homocysteine. These relevant side effects should be thoroughly investigated, as reduced vitamin levels could be easily supplemented, and homocysteine is considered an independent risk factor for cardiovascular diseases. In contrast to newer ASMs, the influences of traditional ones such as carbamazepine and valproate were examined more frequently. However, studies yielded controversial results, which prompted further and comprehensive investigations. Therefore, this study aimed to test the influences of commonly used ASMs on the metabolism of vitamin B12 and compare them with existing literature. Data from a total of 883 epilepsy outpatients at the university hospital of Marburg (UKGM) were analyzed retrospectively. All individuals treated with ASMs, for whom diagnostic markers of vitamin B12 metabolism were measured, were included. These markers consistently involved vitamin B12 and folate serum levels, and in some cases, additionally homocysteine, holotranscobalamin and methylmalonic acid. Following statistical adjustments for age and gender, two approaches were employed. Using analysis of covariance (ANCOVA), mean differences in diagnostic markers between carbamazepine, lamotrigine, levetiracetam, and valproate taken as monotherapy were examined. In a second step, the influence of dose or serum levels of nine ASMs taken in combination therapy was assessed using multiple linear regression. The results showed significantly lower folate levels in patients taking carbamazepine (p < 0.001) compared to other ASMs both in monotherapy and combination therapy. Data of this study suggests that oral folate supplementation could potentially normalize serum levels. Without influencing vitamin B12 and holotranscobalamin levels, significantly higher methylmalonic acid levels were observed in patients taking topiramate yielded in multiple linear regression. Additionally, valproate demonstrated significantly higher vitamin B12 levels, associated with higher levels of holotranscobalamin and lower methylmalonic acid. All effects were found to be dependent on both ASM dose and serum levels. Lamotrigine, levetiracetam, lacosamide, oxcarbazepine, pregabalin and zonisamide on the other hand exhibited no relevant influences on the measured values. In comparison to other studies, the decreasing impact of carbamazepine on folate, potentially leading to elevated homocysteine levels, is approved, although it did not reach a level of significance in this study due to small sample sizes. While in previous studies patients with a therapy of topiramate exhibited reduced vitamin B12 and folate serum levels combined with elevated homocysteine levels, in this study predominantly methylmalonic acid levels were increased while other markers of vitamin B12 metabolism did not show relevant changes. Increased levels of vitamin B12 and holotranscobalamin were found in patients taking valproate while methylmalonic acid levels were reduced. To investigate the underlying mechanisms and clinical relevance of the results further studies are necessary, especially regarding higher methylmalonic acid levels in patients taking topiramate and higher vitamin B12 levels in patients taking valproate. Therefore, vitamin B12 metabolism should be monitored closely in patients taking carbamazepine, topiramate and valproate, and supplementation should be initiated in case of deficiency. Due to the folate-reducing effect of carbamazepine and the associated increase in homocysteine, indications should be critically examined and different ASMs should be preferred in case of additional cardiovascular risk factors.