l-Carnitine Supplementation in Childhood Epilepsy: Current Perspectives (original) (raw)
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Carnitine deficiency in epileptic children treated with a diversity of anti-epileptic regimens
The Egyptian journal of neurology, psychiatry and neurosurgery, 2018
Carnitine deficiency is relatively common in epileptic patients. The risk factors reported include the combination of valproic acid with other antiepileptic drugs (AEDs), young age, multiple neurologic disabilities, non-ambulatory status, and being underweight. To study the level of carnitine deficiency and its associated risk factors among a group of children with idiopathic epilepsy treated with different AEDs. Fifty children with idiopathic epilepsy and 40 age-matched controls were enrolled. For all, serum carnitine level was measured by enzyme-linked immune sorbent assay (ELISA). The mean carnitine level was lower in cases compared to controls ( = 0.04). Patients receiving monotherapy treatment had a high percentage of carnitine deficiency compared to controls ( = 0.04). Patients receiving valproate with other AEDs had a lower level of carnitine compared to controls ( = 0.03). The age of the patients, the duration of treatment, and the doses of different AEDs were not risk facto...
Brain and Development, 2006
This study was performed to evaluate carnitine deficiency in a large series of epilepsy children and adolescents treated with old and new antiepileptic drugs with or without ketogenic diet. Plasma free carnitine was determined in 164 epilepsy patients aged between 7 months and 30 years (mean 10.8 years) treated for a mean period of 7.5 years (range 1 month-26 years) with old and new antiepileptic drugs as mono or add-on therapy. In 16 patients on topiramate or lamotrigine and in 11 on ketogenic diet, plasma free carnitine was prospectively evaluated before starting treatment and after 3 and 12 months, respectively. Overall, low plasma levels of free carnitine were found in 41 patients (25%); by single subgroups, 32 out of 84 patients (38%) taking valproic acid and 13 of 54 (24%) on carbamazepine, both as monotherapy or in combination, showed low free carnitine levels. A higher though not statistically significant risk of hypocarnitinemia resulted to be linked to polytherapy (31.5%) versus monotherapy (17.3%) (PZ.0573). Female sex, psychomotor or mental retardation and abnormal neurological examination appeared to be significantly related with hypocarnitinemia, as well. As to monotherapy, valproic acid was associated with a higher risk of hypocarnitinemia (27.3%) compared with carbamazepine group (14.3%). Neither one of the patients on topiramate (10), lamotrigine (5) or ketogenic diet (11) developed hypocarnitinemia during the first 12 months of treatment. Carnitine deficiency is not uncommon among epilepsy children and adolescents and is mainly linked to valproate therapy; further studies are needed to better understand the clinical significance of serum carnitine decline. q
Carnitine level in Chinese epileptic patients taking sodium valproate
Pediatric Neurology, 2003
Previous studies have demonstrated that carnitine levels were lower in patients taking valproate, especially in those who are younger than 24 months of age, those with concomitant neurologic or metabolic disorders, and those on multiple antiepileptic drugs. We performed a cross-sectional surveillance study on pediatric patients taking valproate to evaluate the relationship between carnitine levels and demographic data including age, daily dosage of valproate, number of antiepileptic drugs, body mass index, and feeding problems. Among the 43 patients studied, only two patients were found to have carnitine levels below the normal limit. There were no statistically significant associations between carnitine levels and age, body mass index, additional antiepileptic drugs used, presence of mental retardation, cerebral palsy, or feeding problems, nonambulatory status, or dosage of valproate. We conclude that routine carnitine level checking is not justified in pediatric patients taking valproate.
Serum and muscle carnitine levels in epileptic children receiving sodium valproate
Journal of child neurology, 2009
The purpose of this study was to determine whether children with epilepsy undergoing valproate therapy and who are otherwise healthy have lower levels of serum and muscle carnitine. A total of 50 patients with epilepsy, 3 to 14 years of age, who were treated solely with valproate and free of abnormal neurologic findings or nutritional problems were selected. The control group consisted of 30 healthy children. The total carnitine levels in serum were 28.1 +/- 10.3 and 55.6 +/-7.3 microg/mL, and the free carnitine levels in serum were 16.5 +/-10.2 and 44.6 +/-7.3 microg/mL, the total carnitine levels in muscle were 12.1 +/- 1.8 and 45.3 +/- 5.9 micromol/g noncollagen protein and the free carnitine levels in muscle were 5.6 +/- 1.6 and 39.3 +/- 6.0 micromol/g noncollagen protein in the valproic acid-treated and control groups, respectively (P < .05). In conclusion, valproate monotherapy depletes both muscle and serum carnitine levels in otherwise healthy epileptic children.
2021
Background: Long-term use of valproic acid is associated with a high level of blood ammonia related to carnitine deficiency. This study investigates the effect of carnitine supplementation on blood ammonia levels in children with epilepsy who have been treated with valproic acid for more than six months. Materials and Methods: This was a randomized, double-blind, placebo-controlled trial study where children with epilepsy who were treated with valproic acid were randomly allocated to the carnitine supplementation and control group. All children were followed for month, and then measured for blood ammonia level. Blood ammonia levels of both groups were compared using an Independent t-test with a significant of p <0.05. Results: Total of 32 children with epilepsy were enrolled as subjects in this study, with 16 children in carnitine group, and 16 children in control group. Among the subjects, 50% were male and 50% were female, with a mean age of 6.5 years old. The average duration ...
Evaluation of valproate effects on acylcarnitine in epileptic children by LC–MS/MS
Brain and Development, 2011
Background: Valproate (VPA) is a simple fatty acid and a substrate for the fatty acid b-oxidation pathway. Previous data suggested that the toxicity of VPA may be provoked by carnitine deficiency and the inhibition of mitochondrial b-oxidation. Objective: The aim of the present study was to elucidate the effect of VPA treatment on carnitine and isomer-differentiated acylcarnitine disposition, and determined the relationships between acylcarnitines and blood VPA levels in long-term treated patients with VPA and/ or other antiepileptic drugs. Methods: Serum samples were obtained from children aged 1-15 years old treated for at least 6 months with VPA alone (n = 28) or VPA combined with other anticonvulsants (n = 23) and untreated controls (n = 23). Serum acylcarnitines were separated from their isomers and quantified using high-performance liquid chromatography-tandem mass spectrometry. Results: We found higher 3-hydroxyisovalerylcarnitine levels and trace amounts of valproylcarnitine in both VPA monotherapy and polytherapy patients. Other acylcarnitines, hexanoylcarnitine, C12, C14:1-carnitines and the ratio of long-chain acylcarnitine to free carnitine were also higher in VPA polytherapy individuals than in controls. VPA monotherapy does not result in decreases in free carnitine or in the accumulation of long-chain acylcarnitines. Blood VPA concentrations correlated positively with hexanoylcarnitine, C12, C14:1, C16:1, C18:1-carnitines in all VPA-treated children (n = 51). Conclusion: Long-term VPA treatment in pediatric patients could affect some specific acylcarnitines, which is enhanced by the concomitant use of other anticonvulsants, and the formation of valproylcarnitine alone seems insufficient to develop severe carnitine deficiency at therapeutic doses of VPA.
Clinical Biochemistry, 2001
The effect of administration of the antiepileptic drug valproate (VPA), on the composition of the plasma acylcarnitine profile (including free carnitine) was investigated. Design and methods: Plasma samples were obtained from 18 individuals (13(:5&; 15-65y) on long-term treatment with VPA (resulting in plasma levels of 14.6 -135.0 mg/L; therapeutic conc.: 40 -100 mg/L). Acylcarnitines (AC) in plasma were quantified by electrospray tandem mass spectrometry (ESI-MS/MS). Results: VPA was found to increase the levels (mean Ϯ SD, M) of 3-hydroxy-isovalerylcarnitine (0.10 Ϯ 0.04; controls: 0.02-0.06), C14:2 acylcarnitine (0.11 Ϯ 0.05; controls: 0.02-0.08), propylglutarylcarnitine (0.06 Ϯ 0.05; controls: 0.00 -0.04), and C18-0Hacylcarnitine (0.09 Ϯ 0.05; controls: 0.00Ϫ0.04). The free carnitine (C) (42.2 Ϯ 9.0; controls: 22.3-54.9) and the total carnitine (52.3 Ϯ 10.1; controls: 26.5-73.6) were not significantly altered by VPA. Other AC (C2-C18, monounsaturated and hydroxylated) were all within the control range and especially no increase of C8 (valproyl) carnitine was observed. A positive correlation was found between the ratios [AC] / [C] (p Ͻ 0.05) or [long-chain AC (C10-C18)] / [C] (p Ͻ 0.09) with the plasma VPA concentration. Conclusions: The unequivocal increase in 3-hydroxy-isovalerylcarnitine is consistent with the increase of 3-hydroxy-isovaleric acid observed in urine of VPA treated patients. This finding suggests an interaction mechanism of VPA with specific enzymes, namely involved in leucine metabolism. Adult patients under VPA monotherapy do not suffer from carnitine deficiency; the effect of the accumulating acylcarnitines is ill-defined.
Carnitine Ester Excretion in Pediatric Patients Receiving Parenteral Nutrition
Pediatric Research, 1990
ABSTRAm. Carnitine plasma concentrations and the ex-(I) and regenerating intramitochondrial coenzyme A through cretion of carnitine and individual carnitine esters were transport of acyl-groups out of the mitochondria, thereby maindetermined in 25 children and adolescents with gastroin-taining conditions required for oxidative processes (2). testinal diseases receiving carnitine-free parenteral nutri-Although carnitine is synthesized de novo in mammalian tion for at least 1 mo using radiochemical and radioisotopic tissues (3). nutritional carnitine deficiency may occur under exchange HPLC methods. Children ~12-y-old usually had certain circumstances if carnitine is not provided with the diet. carnitine plasma concentrations C-2 SD from the normal Infants receiving carnitine-free TPN are particularly prone to mean for age, whereas patients >12-y-old had carnitine develop carnitine deficiency, probably due to impaired carnitine plasma concentrations within the normal range. Age was biosynthesis (4) and low carnitine tissue stores (5). Moreover, the only variable to correlate significantly with plasma infants on TPN appear to have a decreased capacity to oxidize carnitine concentrations during parenteral nutrition. Free fatty acids that can be improved by L-carnitine supplementation carnitine (FC) excretion was closely correlated with plasma (6, 7). The question has therefore been raised whether carnitine FC concentrations and minimal at values <25 rmol/L. The should be considered an essential nutrient for the infant (8). excretion of FC and short-chain acylcarnitines was reduced It is not known at what time during human development by an order of magnitude in younger compared with older endogenous carnitine biosynthesis becomes adequate. Adults patients and controls, but the excretion of "other" acylcar-receiving TPN maintain a normal carnitine status over a longer nitines was less affected. Some of the latter were tentatively period of time than infants (9). Nonetheless. abnormally low identified using gas-liquid chromatographic and mass spec-carnitine plasma concentrations were found in 35% of an adult troscopic techniques as unsaturated and/or branched me-population on long-term home PN (10). Some of them also had dium-chain carnitine esters with a carbon chain of C8-decreased liver carnitine content. The pathogenesis of this is not C10. The results suggest that FC and short-chain acylcar-understood because, in the mature individual, endogenous carnitine are conserved by the kidney in nutritional carnitine nitine biosynthesis should be adequate if precursors are provided deficiency but that there may be an obligatory renal excre-with TPN. However, loss of carnitine through the kidney may tion of other carnitine esters that contributes to the devel-be an important factor. opment of hypocarnitinemia in the younger age group.