Administration Of L-acetylcarnitine Research Articles

Poor Efficacy of L-Acetylcarnitine in the Treatment of Asthenozoospermia in Patients with Type 1 Diabetes.

Introduction. In recent years, research has focused on the impact that diabetes mellitus (DM) has on male reproductive function. The available evidence has mainly considered type 2 DM (DM2). However, we have previously shown that type 1 DM (DM1) also affects male reproductive health. Given the efficacy of carnitine in the treatment of male infertility, a topic that merits further investigation is its role in the treatment of infertile patients with DM1. Aim. To investigate the efficacy of carnitines for the treatment of asthenozoospermia in DM1 patients. Methods. This was a two-arm single-blind, randomized control trial. The patients enrolled in this study were assigned to the group receiving L-acetylcarnitine (LAC) (1.5 g daily for 4 months) or to the group receiving LAC (same dosage) plus L-carnitine (LC) (2 g daily for 4 months). Serum-glycated hemoglobin levels did not differ significantly after either of the two treatments given. Administration of LAC plus LC showed greater efficacy on progressive sperm motility than single therapy (increase 14% vs. 1% after treatment, respectively). Discussion. The results of this study showed that the administration of LAC plus LC is more effective than the administration of LAC alone. The lower efficacy of LAC alone could be due to the lower overall administered dosage. Alternatively, a selective defect of carnitine transporters at an epididymal level could be hypothesized in patients with DM1. Further studies are needed to clarify this point.

Modulatory effects of l-carnitine plus l-acetyl-carnitine on neuroendocrine control of hypothalamic functions in functional hypothalamic amenorrhea (FHA)

Functional hypothalamic amenorrhea (FHA) is a relatively frequent disease due to the combination of metabolic, physical, or psychological stressors. It is characterized by the low endogenous GnRH-induced gonadotropin secretion, thus triggering the ovarian blockade and a hypoestrogenic condition. Up to now various therapeutical strategies have been proposed, both using hormonal treatment as well as neuroactive compounds. Since carnitine, namely l-acetyl-carnitine (LAC), has been demonstrated to be effective in the modulation of the central hypothalamic control of GnRH secretion, we aimed to evaluate whether a combined integrative treatment for 12 weeks of LAC (250 mg/die) and l-carnitine (500 mg/die) was effective in improving the endocrine and metabolic pathways in a group of patients (n = 27) with FHA. After the treatment, interval mean LH plasma levels increased while those of cortisol and amylase decreased significantly. When patients were subdivided according to baseline LH levels, only hypo-LH patients showed the significant increase of LH plasma levels and the significant decrease of both cortisol and amylase plasma levels. The increased 17OHP/cortisol ratio, as index of the adrenal activity, demonstrated the reduced stress-induced adrenal activity. In conclusion, our data sustain the hypothesis that the integrative administration of LAC plus l-carnitine reduced both the metabolic and the neuroendocrine impairment of patients with FHA.

Branched chain amino acids supplemented with L-acetylcarnitine versus BCAA treatment in hepatic coma: a randomized and controlled double blind study

Our earlier study has demonstrated that the administration of L-acetylcarnitine (LAC) improves neurological symptoms and serum parameters in hepatic coma. The aim of this work has been to evaluate the efficacy of the LAC and branched chain amino acids (BCAA) versus BCAA, administered in intravenous infusion, in patients with cirrhotic hepatic coma. Forty-eight highly selected patients were enrolled in the study and, after randomization, received blindly LAC+BCAA (n=24) versus BCAA (n=24). The two groups were similar in age, sex, pathogenesis of cirrhosis, and severity of liver disease. The comparison between values before and after LAC planned treatment showed statistical significant differences in neurological findings, evaluated by the Glasgow Scale, ammonia serum levels, blood urea nitrogen, and EEG. After 60 min of the study period, the LAC+BCAA treated patients compared with BCCA treated showed a significant decrease of ammonia serum levels: 41.20 versus 10.40 mumol P<0.05. After 1 day of the study period, the LAC+BCAA treated patients compared with BCCA treated patients showed a significant increase of Glasgow's score: 3.60 versus 1.50 score P<0.05; a significant decrease of ammonia serum levels: 63.30 versus 27.00 mumol P<0.01; a significant improvement of EEG cps/s: 2.70 versus 0.6 P<0.001. No side-effects were observed in our study series. Our study demonstrated that the administration of BCAA supplemented with LAC might improve neurological symptoms and serum ammonium levels in selected cirrhotic patients with hepatic coma.

Energy metabolism of synaptosomal subpopulations from different neuronal systems of rat hippocampus: effect of L-acetylcarnitine administration in vivo.

The maximum rate (Vmax) of some enzyme activities related to glycolysis, Krebs' cycle, acetylcholine catabolism and amino acid metabolism were evaluated in different types of synaptosomes obtained from rat hippocampus. The enzyme characterization was performed on two synaptosomal populations defined as "large" and "small" synaptosomes, supposed to originate mainly from the granule cell glutamatergic mossy fiber endings and small cholinergic nerve endings mainly arising from septohippocampal fiber synapses, involved with cognitive processes. Thus, this is an unique model of pharmacological significance to study the selective action of drugs on energy metabolism of hippocampus and the sub-chronic i.p. treatment with L-acetylcarnitine at two different dose levels (30 and 60 mg x kg(-1), 5 day a week, for 4 weeks) was performed. In control animals, the results indicate that these two hippocampal synaptosomal populations differ for the potential catalytic activities of enzymes of the main metabolic pathways related to energy metabolism. This energetic micro-heterogeneity may cause their different behaviour during both physiopathological events and pharmacological treatment, because of different sensitivity of neurons. Therefore, the micro-heterogeneity of brain synaptosomes must be considered when the effect of a pharmacological treatment is to be evaluated. In fact, the in vivo administration of L-acetylcarnitine affects some specific enzyme activities, suggesting a specific molecular trigger mode of action on citrate synthase (Krebs' cycle) and glutamate-pyruvate-transaminase (glutamate metabolism), but mainly of "small" synaptosomal populations, suggesting a specific synaptic trigger site of action. These observations on various types of hippocampal synaptosomes confirm their different metabolic machinery and their different sensitivity to pharmacological treatment.

Recurrent and reciprocal inhibition of the human monosynaptic reflex shows opposite changes following intravenous administration of acetylcarnitine

A long-latency, long-lasting increase in the recurrent inhibitory effect on the soleus monosynaptic (Hoffmann, H) reflex was induced after intravenous administration of L-acetylcarnitine, a substance known to process central cholinergic activity. This effect was paralleled by disappearance of the H reflex inhibition (functionally disinhibition) induced by stimulation of Ia afferent fibres from the tibialis anterior (reciprocal inhibition) and gastrocnemius medialis muscle. Magnitude and time course of the L-acetylcarnitine-induced effects were significantly correlated. The data suggest that (1) the L-acetylcarnitine depression of the reciprocal inhibition is mediated by excitation of Renshaw cells impinging on Ia interneurones (INs), and (2) the inhibitory effect of GM Ia afferents onto Sol is mediated by INs subjected to Renshaw inhibition. The results point to the similarity in the wiring of the 'output stage' circuit between cat and humans, and provide a method for testing this network in man.