Carnosine trials re: seizures, tourette's, apraxia and autism

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What is Carnosine?

The supplement that you are interested in learning more about

contains 200mg powdered carnosine, as well as powdered Vitamin E (25

IU) and powdered Zinc (2.5 mg). The exact dosage that is correct for

your child should be established by your doctor in coordination with

Dr. Chez, who pioneered the use of this supplement in

children with developmental delays. L-carnosine, or " carnosine, " is

an amino acid dipeptide made up of histidine and alanine. 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 " neuro protection. " These investigations aimed to examine

protective action since carnosine may be protective of muscle and

nerve function. 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 antiepileptic

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-

Gastault 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-Gastault 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.

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Sallie Bernard

Executive Director

Safe Minds

14 Commerce Drive, 4th Floor

Cranford, NJ 07016

908 276-8032

f - 908 276-1301

www.safeminds.org