Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid

Karabi̇ber, Hamza; Sönmezgöz, Ergün; Özerol, Elif; Yakıncı, Cengiz; Otlu, Barış; Yoloğlu, Saim

doi:10.1016/s0387-7604(02)00163-8

Cited by 119 publications

(111 citation statements)

References 10 publications

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“…In addition, sample sizes were small, and data are lacking for most of the newer AED. [10][11][12][13][14] Thus, valid and detailed data on the association of the commonly used AED with folate and vitamin B12 serum levels are missing.…”

Section: Objectivementioning

confidence: 99%

Antiepileptic drugs interact with folate and vitamin B12 serum levels

Linnebank

Moskau

Semmler

et al. 2011

Annals of Neurology

122

102

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OBJECTIVE: Antiepileptic drugs (AEDs) are important for the treatment of epilepsy, psychiatric diseases, and pain syndromes. Small studies have suggested that AED treatment reduces serum levels of folate and vitamin B12. METHODS: This prospective monocenter study aimed at testing the hypothesis that AED treatment is associated with folate and vitamin B12 serum levels in a large population. A total of 2730 AED-treated and 170 untreated patients with epilepsy and 200 healthy individuals were enrolled. RESULTS: Treatment with carbamazepine, gabapentin, oxcarbazepine, phenytoin, primidone, or valproate was associated with lower mean serum folate levels or with a higher frequency of folate levels below the reference range in comparison with the entire group of patients, untreated patients, or controls. Treatment with phenobarbital, pregabalin, primidone, or topiramate was associated with lower vitamin B12 levels compared with the entire group of patients. Vitamin B12 serum levels were higher in patients treated with valproate compared with the entire group of patients, untreated patients, and healthy controls. Folate or vitamin B12 levels below the reference range were associated with higher mean corpuscular volume (MCV) and higher homocysteine plasma levels. Vitamin substitution for 3 months in 141 patients with folate or vitamin B12 levels below the reference range yielded normal vitamin levels in 95% of the supplemented patients and reduced MCV and homocysteine plasma levels. INTERPRE-TATION: Treatment with most of the commonly used AEDs is associated with reduced folate or vitamin B12 serum levels and is a risk factor for hyperhomocysteinemia. Oral substitution is effective to restore vitamin, MCV, and homocysteine levels.

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Section: Objectivementioning

confidence: 99%

Antiepileptic drugs interact with folate and vitamin B12 serum levels

Linnebank

Moskau

Semmler

et al. 2011

Annals of Neurology

122

102

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“…Some antiepileptic drugs have been shown to cause hyperhomocysteinemia by decreasing serum folate levels [1,[4][5][6]. Karabiber et al found significantly lower serum folate levels and higher homocysteine levels in CBZ group compared to the control group [1].…”

Section: Discussionmentioning

confidence: 99%

“…Apeland et al have observed a decrease in folic acid levels and an increase in homocysteine levels in 42 adult patients taking CBZ as monotherapy [5]. Vitamin B12 levels have been shown to change according to the antiepileptic medication used [1,17,18]. It has been reported that CBZ treatment has decreased vitamin B12 levels and increased homocysteine levels [19][20][21].…”

Section: Discussionmentioning

confidence: 99%

“…Folic acid and vitamin B12 are required for the conversion of homocysteine to methionine. Serum folic acid and vitamin B12 levels may be influenced by antiepileptic drug usage [1][2][3][4][5][6]. Some antiepileptic drugs have been reported to decrease serum thyroxine levels; however the patients have remained clinically euthyroid [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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The effects of oxcarbazepine treatment on vitamin B12 and folate levels, thyroid functions, sex hormones, and bone mineral density in epileptic patients

et al. 2009

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AbstractThe aim of this study was to evaluate vitamin B12 and folate levels, thyroid functions, sex hormones and bone mineral density in idiopathic epileptic patients taking oxcarbazepine as monotherapy. Newly diagnosed pediatric patients with idiopathic partial epilepsy taking oxcarbazepine (OXC) as monotherapy were enrolled in this study. The pre-treatment and 6 months post-treatment values of vitamin B12, folate, thyroid functions, sex hormones, and bone mineral density (BMD) were obtained from all patients. A total of 32 patients (22 (68.8%) males and 10 (31.2%) females) were included in this study. The mean age was 7.4 ± 3.2 years (range: 2–14 years). There were no significant differences between the pre-treatment and 6 months post-treatment values of vitamin B12, folate, thyroid functions, sex hormones, and BMD. However, the 6 month post-treatment sex hormone binding globulin (SHBG) values (159.92 ± 48.14 nmol/L) were significantly higher than the pre-treatment values (137.88 ± 43.12 nmol/L) (p=0.009). We found that OCX treatment in children did not have an effect on serum folate and vitamin B12 levels, thyroid functions, sex hormones and BMD but caused increased SHBG. Over time, the increase in serum SHBG levels may lead to diminished bioactivity of sex steroids, and thus to reduced fertility. The further studies are needed to demonstrate the clinical importance of increased SHBG levels.

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“…Recently, it has been demonstrated that the oxidative modification of LDLs in the endothelial microenvironment is a damaging factor that can be modified with fat-soluble antioxidant vitamins (46,47,142). Many prospective studies have demonstrated that a multi-ingredient vitamin formula (vitamin B6, vitamin B12, folate, vitamin C, vitamin E and β-carotene) with antioxidant properties has measurable effects on Hcy and LDL-c oxidation indices (29,30).…”

Section: Discussionmentioning

confidence: 99%

The High Atherosclerotic Risk Among Epileptics: the Atheroprotective Role of Multivitamins

Hamed

Nabeshima

2005

J Pharmacol Sci

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Abstract. Neurologists have little concern about the high atherosclerotic risk among epileptics. Recent evidences mount that chronic epilepsy and prolonged use of antiepileptic drugs (AEDs) are associated with multiple risk factors that are critically implicated in pathobiology and dysfunction of the vessel wall through complex molecular mechanisms that promote atherogenesis. This review is concerned with three metabolic alterations, which are attributed as major risk factors for atherosclerosis among epileptics: altered metabolism of a) homocysteine (Hcy), b) lipids and lipoproteins, and c) uric acid. Most conventional AEDs reduce folic acid levels, thereby raising Hcy levels. Hyperhomosysteinemia is recently believed to induce endothelial dysfunction and promote atherosclerosis through complex oxidative and excitatory neurotoxic molecular mechanisms. However, Hcy itself is a convulsing substance with increased seizure recurrence and intractability to antiepileptic medications. AEDs can disturb lipid metabolism with resultant hypercholestrolemia and dyslipidemia, common recognized risks for atherosclerosis. Altered uric acid metabolism is common among epileptics. Uric acid has been implicated in endothelial cell damage and decreased endothelial nitric oxide bioavailability. In the presence of atherosclerotic milieu, uric acid interacts with other substrate toxicities and increased reactive oxygen species, accelerating atherosclerosis. The above information forms the rationale for future routine screening and correction of such metabolic alterations in epileptics. A convincing argument now develops that routine polyvitamin supplementation (folic acid, vitamin B12, vitamin B6, vitamin C, vitamin E, and β-carotene) becomes increasingly important for women and men receiving AEDs at all ages. The atheroprotective effect of multivitamins is through their antioxidant and anti-inflammatory effects together with their lipid and Hcy lowering effects.

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Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid

Cited by 119 publications

References 10 publications

Antiepileptic drugs interact with folate and vitamin B12 serum levels

Antiepileptic drugs interact with folate and vitamin B12 serum levels

The effects of oxcarbazepine treatment on vitamin B12 and folate levels, thyroid functions, sex hormones, and bone mineral density in epileptic patients

The High Atherosclerotic Risk Among Epileptics: the Atheroprotective Role of Multivitamins

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