title: Acetyl-L-carnitine (ALC) in attention-deficit/hyperactivity disorder: a multi-site, placebo-controlled pilot trial. [L-acetylcarnitine treatment on fragile X patients hyperactive behaviour]. Efficacy of carnitine in the treatment of children with attention-deficit hyperactivity disorder. Screening for the presence of FMR1 premutation alleles in women with fibromyalgia. Acetyl-L-Carnitine as an Adjunctive Therapy in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Placebo-Controlled Trial Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease A double‐blind, parallel, multicenter comparison of L‐acetylcarnitine with placebo on the attention deficit hyperactivity disorder in fragile X syndrome boys
abstract: OBJECTIVE To determine whether acetyl-L-carnitine ( ALC ) , a metabolite necessary for energy metabolism and essential fatty acid anabolism , might help attention-deficit/hyperactivity disorder ( ADHD ) . Trials in Down 's syndrome , migraine , and Alzheimer 's disease showed benefit for attention . A preliminary trial in ADHD using L-carnitine reported significant benefit . METHOD A multi-site 16-week pilot study r and omized 112 children ( 83 boys , 29 girls ) age 5 - 12 with systematic ally diagnosed ADHD to placebo or ALC in weight-based doses from 500 to 1500 mg b.i.d . The 2001 revisions of the Conners ' parent and teacher scales ( including DSM-IV ADHD symptoms ) were administered at baseline , 8 , 12 , and 16 weeks . Analyses were ANOVA of change from baseline to 16 weeks with treatment , center , and treatment-by-center interaction as independent variables . RESULTS The primary intent-to-treat analysis , of 9 DSM-IV teacher-rated inattentive symptoms , was not significant . However , secondary analyses were interesting . There was significant ( p = 0.02 ) moderation by subtype : superiority of ALC over placebo in the inattentive type , with an opposite tendency in combined type . There was also a geographic effect ( p = 0.047 ) . Side effects were negligible ; electrocardiograms , lab work , and physical exam unremarkable . CONCLUSION ALC appears safe , but with no effect on the overall ADHD population ( especially combined type ) . It deserves further exploration for possible benefit specifically in the inattentive type Hyperactivity is a significant problem for almost all young males affected by fragile X syndrome ( FXS ) , the most common inherited disease causing mental retardation . Therapeutical approaches are actually based on Central Nervous System ( CNS ) stimulants lacking a well defined rationale and efficacy while they further decrease the patient 's limited attention span . A pilot study on 17 fragile X male treated with L-acetylcarnitine ( LAC ) over one year , showed a significant reduction of their hyperactivity behaviour tested by the Conners Abbreviated Parent-Teacher Question naire . LAC use in FXS patients derives from the hypothesis that the biochemical and physiological properties this substance has may preserve brain activity . LAC is a small , hydrosoluble molecule that easily diffuses in the extracellular space and enters any cell in the nervous system through specific transporters . Different cerebral areas use this molecule differently to metabolize glucose and lipids to provide for ATP and neurotrasmitters synthesis . The acetyl group LAC carriers represents a key metabolic signaling element possibly mediating its effect in the CNS . The exogenous administration of LAC may affect brain activity in FXS by : I ) modulation of fuel partitioning for energy production , which at the mithocondrial level is associated with the Kreb 's cycle metabolic role in neurotransmitter synthesis ; II ) remodelling of lipid membrane in terms of LAC actively determining the production of polyunsaturated fatty acids ; III ) preferential effect on the attention component of the cholinergic system which relies on its peculiar modality of communication in the CNS . Based on the above premises an explorative , double-blind , placebo controlled , multicenter study is ongoing . A total population of 160 children from nine European centers will be enrolled . The objective of this study is to determine the effect of LAC on the hyperactive behaviour of FXS children as evaluated by the administration of the Conners Abbreviated Parent Question naire To determine safety and the efficacy of carnitine treatment in children with attention-deficit hyperactivity disorder ( ADHD ) . The ADHD behavior was observed by parents completing the Child Behavior Checklist ( CBCL ) and by teachers completing the  Conners teacher-rating score  , in a r and omized , double-blind , placebo-controlled double-crossover trial . In 13/24 boys receiving carnitine  , home behavior improved as assessed with the CBCL total score ( P < 0.02 ) . In 13/24 boys , school behavior improved as assessed with the Conners teacher-rating score ( P < 0.05 ) . Before treatment , the CBCL total and sub-scores were significantly different from those of normal Dutch boys ( P < 0.0001 ) . Responders showed a significant improvement of the CBCL total scores compared to baseline ( P < 0.0001 ) . In the majority of boys no side effects were seen . At baseline and after carnitine treatment , responders showed higher levels of plasma-free carnitine ( P < 0.03 ) and acetylcarnitine ( P < 0.05 ) . Compared to baseline , the carnitine treatment caused in the responsive patients a decrease of 20 - 65 % ( 8 - 48 points ) as assessed by the CBCL total problem rating scale . Treatment with carnitine significantly decreased the attention problems and aggressive behavior in boys with ADHD Fibromyalgia is a chronic condition characterized by widespread pain , fatigue , non-restorative sleep and cognitive difficulties that affects 2 - 4 % of the general population . Recently a possible relationship between the FMR1 premutation and fibromyalgia has been pointed out . In attempt to gather more data we screened for the  FMR1 CGG expansion 700 DNA sample s from unrelated fibromyalgia patients . This data might be useful for evaluating the incorporation of this test in rheumatologic procedures for women with fibromyalgia . The observed frequency of  FMR1 premutation carriers ( 3 of 700 , 0.4 % ) is not significantly different from the estimated rate in the general female population ( 1/250 - 1/400 ) ( P=0.539 , P=0.716 ) . Clinical examination of the FMR1 premutation carriers identified revealed that all of them had important neurological symptoms with regard to muscular symptoms , neurocognitive alterations and neurovegetative impairments . With regard to other clinical aspects of the disease the cases apparently did not differ from the average fibromyalgia patients . On the basis of our results an FMR1 screening among fibromyalgia female patients would not be recommended . However it would be worthwhile to further evaluate the different clinical presentations that fibromyalgia patients might present based on their FMR1 premutation carrier status The objective of this study was to test whether a previous observed Acetyl-L-carnitine ( ALC ) treatment effect could be repeated in an ALC adjunctive therapy treatment trial of attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents . This was a six-week , r and omized clinical trial undertaken in an outpatient child and adolescent clinic . Subjects included 40 out patients ( 28 boys and 12 girls ) between the ages of 7–13 who met the DSM-IV-TR diagnostic criteria for ADHD . All study subjects were r and omly assigned to receive treatment using capsules of ALC doses ranging from 500 to 1,500 mg/day depending on the weight of the child plus methylpheni date at a dose of 20–30 mg/day depending on weight or Placebo plus methylpheni date at a dose of 20–30 mg/day depending on weight . The principal measure of outcome was the Teacher and Parent attention deficit/hyperactivity disorder Rating Scale- IV . No difference was observed between the two groups on the Parent and Teacher Rating Scale scores ( df = 1 ; F = 0.10 ; P = 0.74 and df = 1 ; F = 0.22 ; P = 0.63 respectively ) . Side effects consisting of headache and irritability were observed more frequently in the methylpheni date plus placebo group . The results of this study do not support the application of ALC as an adjunctive therapy to methylpheni date in children and adolescents with ADHD In a double-blind , placebo study , acetyl-L-carnitine was administered to 7 probable Alzheimer 's disease patients who were then compared by clinical and 31P magnetic resonance spectroscopic measures to 5 placebo-treated probable AD patients and 21 age-matched healthy controls over the course of 1 year . Compared to AD patients on placebo , acetyl-L-carnitine-treated patients showed significantly less deterioration in their Mini-Mental Status and Alzheimer 's Disease Assessment Scale test scores . Furthermore , the decrease in phosphomonoester levels observed in both the acetyl-L-carnitine and placebo AD groups at entry was normalized in the acetyl-L-carnitine-treated but not in the placebo-treated patients . Similar normalization of high-energy phosphate levels was observed in the acetyl-L-carnitine-treated but not in the placebo-treated patients . This is the first direct in vivo demonstration of a beneficial effect of a drug on both clinical and CNS neurochemical parameters in AD 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 methylpheni date ( 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 r and omized , 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 Vinel and 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 . © 2008 Wiley‐Liss ,
target: Regarding the primary outcome of psychological and learning capabilities , both studies assessed the effect of interventions on  children 's verbal and non-verbal intellectual functioning using the Wechsler Intelligence Scale for Children - Revised .
  AUTHORS ' CONCLUSIONS Low- quality evidence from two small trials showed that when compared to placebo , LAC may not improve intellectual functioning or hyperactive behaviour in children with FXS
background: BACKGROUND People with fragile X syndrome ( FXS ) have an intellectual dysfunction that can range from very mild to severe .
  Symptoms can include speech and language delays and behavioural difficulties such as aggression or self injurious behaviours , emotional lability , and anxiety-related problems ( for example obsessive-compulsive symptoms and perseverative behaviours ) .
  In some cases , affected people may have an additional diagnosis of attention deficit hyperactivity disorder or an autism spectrum disorder .
  OBJECTIVES To review the efficacy and safety of L-acetylcarnitine in improving the psychological , intellectual , and social performance of people with FXS .