RESUMEN
Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption ( V ˙ O 2 ) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Carnitina/uso terapéutico , Tolerancia al Ejercicio/efectos de los fármacos , Oftalmoplejía Externa Progresiva Crónica/tratamiento farmacológico , Complejo Vitamínico B/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Prueba de Esfuerzo/efectos de los fármacos , Ácido Láctico/sangre , Miopatías Mitocondriales/tratamiento farmacológico , Fuerza Muscular/efectos de los fármacos , Fosforilación Oxidativa/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Consumo de Oxígeno/fisiología , EspirometríaRESUMEN
Effect of carnitine supplementation in enhancing fat utilization was investigated by looking into its effects on mitochondrial respiratory enzymes activity in liver and muscle as well as on membrane fatty acid profile in rats fed with hydrogenated fat (HF) and MUFA-rich peanut oil (PO) with or without exercise. Male Wistar rats were fed HF-diet (4 groups, 8 rats in each group) or PO-diet (4 groups, 8 rats in each group), with or without carnitine for 24 weeks. One group for each diet acted as sedentary control while the other groups were allowed swimming for 1 hr a day, 6 days/week, for 24 weeks. The PO diet as well as exercise increased the activities of mitochondrial enzymes, NADH dehydrogenase, NADH oxidase, cytochrome C reductase, cytochrome oxidase, while carnitine supplementation further augmented the oxidative capacity of both liver and muscle significantly by enhancing the activity of carnitine palmitoyl transferase and the respiratory chain enzymes. These effects can be attributed to the enhanced unsaturated fatty acids in phospholipids of mitochondria and may be due to increased fluidity of the membrane in these rats. Results of this study show a significant health promoting effects of carnitine supplementation which could be further augmented by regular exercise.
RESUMEN
PURPOSE: This study was designed to investigate whether valproic acid(VPA) induces Reye's syndrome by analyzing blood chemistry, carnitine(CARN) concentration, and the morphologic changes of hepatocytes. The changes of GFAP immunoreactivity of astrocytes were examined in rats with Reye's syndrome induced by VPA. And the effects of CARN supplementation on Reye's syndrome were also investigated. METHODS: Ten rats were assigned to each of the following 3 groups : control group(0.5ml of normal saline), VPA group(250mg/kg of VPA), and VPA plus CARN group(250mg/kg of VPA and 100mg/kg of CARN). Each dose was injected intraperitoneally every 12 hours for 7 days. All rats fasted overnight following the final injection. RESULTS: In the VPA group, the levels of glucose and ketones decreased and the levels of ammonia, SGOT and lactates increased as compared with the control group. Lower levels of free CARN and higher acyl/free CARN ratios, indicating secondary CARN deficiency, were observed, and the appearance of transformed mitochondria of hepatocytes provided further evidence of mitochondrial metabolic dysfunction in Reye's syndrome. The GFAP immunoreactivity and the area percent of GFAP-positive astrocytes in the cingulum decreased in VPA group. In the VPA plus CARN group, there were no significant differences with the control group in blood chemistry, acyl/free CARN ratios and morphology of hepatocytes. However, the GFAP immunoreativity and the percent of GFAP-positive astrocytes in the cingulum decreased as much as in the VPA group. CONCLUSION: It is suggested that CARN supplementation may prevent abnormal findings of blood chemistry, CARN deficiency and the morphologic changes of liver mitochondria due to VPA, but CARN may have little effect on GFAP immunoreactivity of astrocytes in rats with Reye's syndrome induced by VPA.