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Michael G. Chez, M.D., Cathleen P. Buchanan, Ph.D., Jamie L. Komen, M.A., Marina Becker, R.N. Journal of Child Neurology (accepted for publication 2003). Pediatric Neurology, Lake Forest Hospital, Illinois 60045, USA. firstname.lastname@example.org (PubMed – Abstract)
Objective: L-Carnosine is an amino acid dipeptide that may enhance frontal lobe function. We therefore sought to investigate whether L-Carnosine supplementation for children with Autistic Spectrum Disorders (ASD) results in observable, objective changes in language and/or behavior in contrast to placebo.
Design/Methods: Thirty-one children (21 M, mean age= 7.45; range = 3.2-12.5 yrs) meeting inclusion criteria were enrolled in an 8 week blinded trial of either 400 mg BID powdered L-Carnosine or placebo. Children were assessed at a pediatric neurology clinic with the Childhood Autism Rating Scale (CARS), the Gilliam Autism Rating Scale (GARS), the Expressive and Receptive One-Word Picture Vocabulary tests (E/ROWPVT), and biweekly parental Clinical Global Impression of Change (CGI), at baseline and 8 week endpoint. Dr Michael G. Chez is specialist and associate professor in Child Neurology Results: Children who were on placebo (n=17) did not show statistically significant changes on any of the outcome measures. After 8 weeks on L-Carnosine, children (n=14) showed statistically significant improvements on the GARS total score, GARS Behavior, Socialization, and Communication subscales, and the ROWPVT (all p’s<.05). E/ROWPVT and CARS showed trends in improvements, which were supported by parental CGI.
Conclusions: Oral supplementation with 400mg L-Carnosine resulted in demonstrable improvements in autistic behaviors as well as increases in language comprehension that reached statistical significance. Although the mechanism of action of the amino acid is not well understood, it is believed that it acts to modulate neurotransmission and affect metal ion transfer of zinc and copper in the entorhinal cortex. This may enhance neurological function or act in a neuroprotective fashion.
L – C A R N O S I N E
What is Carnosine?
L-carnosine, is a naturally-occurring amino acid found within the human body.The deep frontal part of the brain (entorhinal cortex) is believed to be a site where carnosine tends to accumulate. It may interact with zinc in that area, as well as having effects on GABA, a brain neurotransmitter, which by a complex chemical reaction forms homo-carnosine.
What Studies Have Been Done with Carnosine?
Rat and animal studies have been done with carnosine looking at “neuroprotection.” These investigations aimed to examine protective action since carnosine may be protective of muscle and nerve function, particularly of the heart. There have been no studies that have shown any evidence of toxicity.
Recent MRI studies by Petroff and colleagues (2001) examining levels of brain chemistry showed a relationship between homo-carnosine and GABA in temporal lobe and generalized myoclonic epilepsies.
These authors described homo-carnosine levels that may correlate with seizure control even when GABA response is defective in human studies. Dr. Chez was intrigued by the results of this study, and thus began a study in June, 2001 that aimed to test if supplementing carnosine orally could enhance seizure protection in childrenwho were already on anticonvulsants and who had recurrent seizures despite being on standard drug therapy. He hypothesized that the addition of carnosine could decrease seizure frequency. He supplemented with powdered carnosine, as well as powdered Vitamin E (25IU) and powdered Zinc (2.5 mg).
The Open-Label Study
A total of 75 children, who had “failed” multipleantiepilepticmedications in an effort to stop their seizures (including steroids and the Ketogenic diet) with histories of partial or generalized epilepsy entered the open-label study. The majority had fronto- temporal lobe seizures, or generalized epilepsy. 25% had EEGs to directly compare before and after starting the carnosine. Many patients had reductions in seizure frequency, but without EEG correlation. Two sisters with hypsarrythmia/Lennox-Gastaut wave patterns or Lennox-Gastaut type patterns, EEG amplitude and spike frequency improved with carnosine in dosages of 800-2,000 mg. per day. Dosage was titrated upward depending upon bodyweight. No side effects were reported. Unexpectedly, parental diaries showed a pattern of comments related to gains in cognitive domains including language, alertness, energy levels, and even gross motor ability. Dr. Chez was motivated by such reports in addition to comments from other professionals that worked simultaneously with the children (e.g., speech therapists) who, unaware that children were on the new supplement, spontaneously stated that individual children were showing incremental gains not previously seen. Expressive language was described as more fluent, eye contact more frequent, and interest in the environment was more prominent. Dr. Chez thought that this supplement could be of benefit to children with autism or PDD and so began to give it to children with such diagnoses in an open-label trial. Indeed, parents reported benefits in their children after as few as 2 weeks, in the areas of socialization, expressive language, alertness level, energy level, adaptation to change, and curiously, gross motor planning.
The Double-Blind Study
Because of the remarkable cognitive improvements in language, speech production and school performance as well as social alertness, Dr. Chez felt it important to study the effect of the supplement in children with Autistic Spectrum Disorders. Children were included in this study if they had histories of abnormal EEG, and had previously responded to cognitive-enhancing dementia medications (as part of a controlled study at the office) or to anti-convulsants. A double-blind placebo controlled study with carnosine was begun. Children were randomly placed on either active carnosine or placebo.Expressive and receptive language measures, two autism rating scales, and parent rating analog scales were administered at the start and completion of the study. Results of this study indicated clinically meaningful changes in many aspects of autistic features, and also showed that the carnosine supplement improved children’s expressive and receptive language significantly. This is the only dietary supplement to date studied in a double-blind fashion in autism.
Who Benefits and What are the Side Effects?
The majority of children with either epilepsy or autism treated in open
label studies by Dr. Chez benefited from carnosine supplementation. Dr.
Chez estimates that approximately 10% of children who have been on the carnosine supplement have had reports of no improvement. A very small percentage (less than 5% of children with epilepsy or autistic spectrum disorders) have shown increased physical hyperactivity or verbal hyperactivity, but we are unable to ascertain if these reports are directly related to the carnosine supplement. No sleep disturbances were reported as a result of carnosine therapy even in dosages up to 3,000 mg. a day. No abdominal side effects, skin rashes, or any changes in anticonvulsant blood levels, liver functions or hematological studies. No patients had any urinary changes or bowel habit changes from the carnosine. Many children on the autistic spectrum were reported to increase their range of food choices with an improved range of appetite. Responses have been seen in generalized epilepsies, focal seizure disorders, autism, PDD, and head injury to date. Because of its effect on entorhinal cortex, improvements in Alzheimer’s disease or other frontal lobe encephalopathy may be possible. Any syndrome that involves apraxia or expressive language delay may benefit from this.
Concurrent studies are currently being run or planned in areas of
attention disorder, Tourette’s syndrome, and various learning disability
syndromes of the nonverbal type.
The best way to supplement carnosine is the LifeWave, Carnosine patches. They stimulate the body’s own production of carnosine in a completely safe way. Powdered Carnosine formulas are unpleasant to take and much of it is broken down by digestion. It can be challenging to get a child to cooperate with this.
to find out more about Carnosine patches, go to www.lifewave.com/newwavehealth and look at their Y-Age product which also has glutathione. Both of these in combination have been helping children and adults alike.