Attention deficit hyperactivity disorder (ADHD) is a frequent behavioral problem in young boys with fragile X syndrome (FXS), and its treatment is critical for improving social ability. The short-term efficacy of stimulant medications like methylphenidate (MPH) is well established in children with ADHD. FXS boys treated with MPH have improved attention span and socialization skills; however their mood becomes unstable at higher doses. Therefore, alternative pharmacological treatment of ADHD symptoms is desirable. A recent study showed that carnitine has a beneficial effect on the hyperactive-impulsive behavior in boys with ADHD without side effects. Our previous placebo-controlled trial indicated that L-acetylcarnitine (LAC) reduces hyperactivity in FXS boys. The objective of this study was to determine the efficacy of LAC in a larger sample of FXS boys with ADHD. The study design was randomized, double blind placebo controlled, parallel, and multicenter (with eight centers involved in Italy, France, and Spain). Sixty-three FXS males with ADHD (aged 6-13 years) were enrolled; 7 patients dropped out, 56 completed the one-year treatment, and 51 were included in the statistical analysis. Both groups improved their behavior, showing that psychosocial intervention has a significant therapeutic effect. However, we observed a stronger reduction of hyperactivity and improvement of social behavior in patients treated with LAC, compared with the placebo group, as determined by the Conners' Global Index Parents and the Vineland Adaptive Behavior Scale. Our results show that LAC (20-50 mg/kg/day) represents a safe alternative to the use of stimulant drugs for the treatment of ADHD in FXS children.

Biopsies were taken from the vastus lateralis muscle of 26 chronic uremic patients before and after a 24-week treatment with L-carnitine given at the dose of 2 g i.v. at the end of hemodialysis, or in dialysis solution, or per os twice daily. The aim of the study was to evaluate both the muscle morphology in dialyzed subjects and the modification provoked by the therapy. All patients manifested a significant, even if variable, degree of muscular atrophy which involved all types of muscle fibers. After the treatment there was an increase of about 7% in the diameter of type I and type IIa fibers, which can utilize carnitine for fatty acid oxidation to produce energy, and a reduction in the atrophic fibers. No noteworthy changes were documented in type IIb fibers, which depend on glycolysis for energy production.

In patients with chronic renal failure, not yet undergoing hemodialysis (HD), plasma acylcarnitines accumulate in part due to a decreased renal clearance of esterified carnitine moieties. In these patients, a high acylcarnitine/free-carnitine ratio is usually found in plasma. Patients undergoing maintenance HD, usually present with plasma carnitine insufficiency, due to accumulation of metabolic intermediates combined with impaired carnitine biosynthesis, reduced protein intake and increased removal via HD. Plasma carnitine concentrations rapidly decrease to 40% of baseline level during the dialysis session, with a slow restoration of the carnitine concentration during the interdialytic period, mainly from organs of storage (skeletal muscle). Dietary intake also plays an important role in carnitine homeostasis of HD patients since the prevalence of malnutrition ranges from 18% to 75% of these cases. This could differentially affect various body compartments, with clinical consequences such as impaired muscle function, decreased wound healing, altered ventilatory response, and abnormal immune function. Repeated hemodialytic treatments are associated with decreased carnitine stores in skeletal muscle. The administration of intravenous L-carnitine (LC) postdialysis replenishes the free carnitine removed from the blood and contributes to replenishment of muscle carnitine content. LC supplementation in selected uremic patients may yield clinical benefits by ameliorating several conditions, such as erythropoietin-resistant anemia, decreased cardiac performance, intradialytic hypotension, muscle symptoms, as well as impaired exercise and functional capacities. Furthermore, LC may positively influence the nutritional status of HD patients by promoting a positive protein balance, and by reducing insulin resistance and chronic inflammation, possibly through an effect on leptin resistance.

Efficient utilization of fatty acids to sustain prolonged physical efforts is thought to be dependent on the carnitine shuttle of muscle. A study has been carried out in 24 athletes (13 long-distance runners and 11 sprinters). These subjects received placebo or L-carnitine (1 g/orally b.i.d.) during a 6-month period of training. In endurance athletes, training induced lowering of total and free muscle carnitine. Increase of esterified muscle carnitine was also observed. Post-exertional overflow of acetylcarnitine and long-chain acylcarnitine, as well as reduction of the free fraction was also noticed in the blood. Fasting plasma carnitine levels, however, were not affected in carnitine-treated athletes at rest. These changes were likely related with the significantly increased urinary excretion of esterified and total carnitine which occurred after physical exercise. In the sprinters only, a decrease in free and total carnitine of muscle was detected after training. Both these potentially unfavorable effects were prevented by oral administration of L-carnitine. Our data suggest that training in endurance athletes, and to a lesser extent, in sprinters, is associated with a decrease in free and total carnitine of muscle, due to an increased overflow of short-chain carnitine esters in urine.

We investigated the effect of long-term i.v. administration of L-carnitine on human muscle fibers using morphometric parameters. We administered 2 g/day L-carnitine to patients undergoing hemodialysis for at least 12 months. At the end of this period a marked increase in serum and muscle carnitine levels was observed in all patients, together with hypertrophy and predominance of type 1 fibers, L-carnitine was withheld for 4 months, during which time serum and muscle levels gradually decreased and no changes were observed in muscle fibers. Subsequent addition of L-carnitine to dialysis fluid for another 4 months stabilized lower levels. At the end of this period reduction of diameter of type 1 fibers was observed. Type 2 fibers remained unchanged. Moreover, type 1 fibers remained predominant in all cases. Hence, we suggest that carnitine has a specific trophic effect on type 1 fibers which are characterized by an oxidative metabolism.