L-Carnosine

[RobinN]

I was just reading about more alternatives and ran up on this. I have heard this for autism therapies, but this is the first time I have read studies on it for Epilepsy.

L-carnosine Therapy for Intractable Epilepsy in Childhood: Effect on EEG
Michael G. Chez, M.D., Cathleen P. Buchanan, Ph.D., Jamie L. Komen, M.A.

Objective: L-Carnosine is an amino acid dipeptide that may indirectly affect the electrochemical process in the brain. MRI spectroscopy has recently demonstrated that brain homocarnosine levels may correlate with seizure control. Due to these findings, we decided to examine whether ingesting dietary carnosine would decrease spike and wave activity and improve seizure control both clinically (overt seizures) and physiologically (EEG) by raising homocarnosine levels in the brain.

Design/Methods: Seven children (3 female, 4 male; age range 2-12 years) meeting inclusion criteria were enrolled in a 10 week study, beginning with a baseline EEG reading. Participants were then administered 400mg BID of powdered L-Carnosine for the 10 week time period and a final EEG was subsequently read by Dr. Chez.

Results: After 10 weeks of Carnosine therapy, 5 of the 7 participants documented improved EEG findings and all 7 children exhibited improvement in seizure frequency. While not formally evaluated, improvement in the domains of global cognition, behavior and language function was reported in all 7 participants. While these domains were not predicted to be affected by the L-Carnosine supplementation, they were elicited spontaneously via blinded therapists and family members.

Conslusions: L-Carnosine may be a useful add-on medication for intractable seizure disorders. Although, the exact mechanism is unknown, L-Carnosine is believed to bind with GABA to form homocarnosine in the brain and may also modulate copper and zinc influx into the neurons decreasing the after-discharges and spike-wave discharges associated with many seizure disorders. This may decrease the frequency of clinical seizures and, in some cases, improve EEG patterns.

Citation of Published Abstract:
Chez, Michael G., Buchanan, Cathleen P., and Jamie Komen. L-Carnosine Therapy for Intractable Epilepsy in Childhood: Effect on EEG. Epilepsia 2002; 43(7): 65.

http://www.enzymestuff.com/rtcarnosine.htm

[RobinN]

L - C A R N O S I N E

What is Carnosine?
The naturally-occurring amino acid is found within the human body, a by-product of proteins digested within the 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 nervefunction. There have been no studies that have shown any evidence of toxicity or teratogenicity in animals where carnosine has been studied. Few scientifically-validated human studies have been conducted, however, and most of the information one finds about carnosine's claims are of the quality found on the internet. Claims have been made for generic carnosine/carnosine formulations aiding in combating a range of maladies from Alzheimer's to body building.

Why Carnosine, then?
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 children who 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 and so began an open-label study of carnosine which he acquired via an industrial chemical company.

The Open-Label Study
A total of 75 children, who had "failed" multiple anti-epileptic medications 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. Approximately 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 variant both showed dramatic improvements in EEG amplitude, spike frequency, and background activity. In three other patients with primary or secondary generalized spike and 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.