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Carnosine (L-Carnosine)
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Carnosine - Neurological and Psychiatric disorders
Carnosine is a versatile neuro-protectant
 Evolution has arranged so that young and healthy brain to contain considerable amounts of carnosine which protects these most precious cells against damage and degeneration. The protective mechanisms are the antioxidant function, prevention of glycation and carbonylation, as explained above. In addition, carnosine protects proteasomes which have a central role in the disposal of carbonylated proteins. In this way, carnosine seems to prevent and slow down Alzheimer´s disease and perhaps other types of dementia and mild cognitive impairment.
In chronic brain disorders, Alzheimer´s and Parkinson´s diseases, epilepsy, depression and schizophrenia, oxidation stress prevails and, in addition, all the other hazardous interrelated reactions occur at a high rate. The glycation denatured proteins and phospholipids, and produced AGE´s which in turn add fuel to the oxidation of the lipids in the cell membranes. Oxidative stress increases the activity of an enzyme called phospholipase A2 (PLA2), which in turn break down fatty acids of the cell membranes. All these reactions interfere with the neurotransmitters.
Carnosine antagonizes oxidative stress (Boldyrev et al, 1999) as well as all the harmful reactions. It is therefore a versatile neuro-protectant against all neurological and psychiatric syndromes and disorders.
Carnosine is a multipotent neuroprotectant
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Alzheimer´s disease and mild cognitive impairment (MCI)
Alzheimer's disease is a degenerative disorder of the brain which causes progressive decline in memory and general cognitive abilities. Slowly and inexorably, the disease attacks nerve cells in all parts of the cortex of the brain, as well as some surrounding structures, thereby impairing a person's abilities to govern emotions, recognize errors and patterns, coordinate movement, and remember. At the last, an afflicted person loses all memory and mental functioning. There is no recovery.
Apart from the progressive destruction of nerve cells, a wide range of abnormalities can be seen in the brains of patients who have died from Alzheimer's, including extracellular deposits of amyloid protein and microscopic tangles of fibrils inside nerve cells. In experiments, treatment with carnosine was found to reduce or completely prevent cell damage caused by beta amyloid, the substance found in the brain of Alzheimer's disease patients. Beta amyloid can interact with certain RAGE receptors causing damage to the nerves and arteries of the brain. Carnosine blocks and inactivates beta amyloid, so it protects neural tissues against dementia.
Moreover, carnosine protects the brain cells by fighting the highly toxic alpha,beta-unsaturated aldehyde acrolein which is formed during the peroxidation of polyunsaturated lipids, raising the possibility that it functions as a 'toxicological second messenger' during oxidative cell injury (Burcham et al. 2000).
Recent research also confirms that the toxic unsaturated aldehyde crotonaldehyde (CA) contributes to carbonylation resulting in protein damage during lipid peroxidation (Fontaine et al 2002). As carnosine combats all aldehydes, it offers another explanation for its benefits in prevention of Alzheimer´s disease and other conditions with oxidative stress.
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Dr Alois Alzheimer
(1864-1915)
Brain scan of an Alzheimer´s
patient. The pink area represents destroyed brain
tissue.
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Metal chelation by carnosine may prevent and slows down Alzheimers.
Some laboratory studies have reported excessive amounts of metal ions such as zinc, copper in Alzheimer´s brain. Such ions may possibly change the chemical architecture of normal beta amyloid, making it more harmful. A mildly acidic environment appears to be important in the process that binds these metals to beta amyloid. Experts observe that such conditions (acidic environment and higher levels of zinc and copper) commonly occur as part of the inflammatory response to local injury. Carnosine has the unique ability to chelate copper, zinc and other metals, and to remove them from the body, as explained above in the section Metal Chelation. This may be an important function of carnosine in preventing and slowing down Alzheimer´s and other degenerative brain disorders.
MEDLINE data base includes at this writing nine documents on the relationship between carnosine and Alzheimer´s. If you want to read them, search for "carnosine; Alzheimer", and click "go".
Mild cognitive impairment
Mild cognitive impairment (MCI) is a recently described syndrome that is currently thought of as a transition phase between healthy cognitive ageing and dementia. Recent evidence suggests that the aetiological heterogeneity among individuals with MCI could be greater than previously reported. For example, cerebrovascular disease seems to be underestimated as a potential cause of MCI. The general nature of MCI makes accurate accounting of the prevalence, prognosis, and potential benefit from treatment somewhat difficult. However, carnosine, as a potent neuro-protectant, seems to be an ideal supplement for people with apparent or suspected mild cognitive impairment.
Carnosine prevents proteasomal decline in Alzheimer's disease
The main reason for brain cell destruction in Alzheimer´ is probably the inhibition of the proteasome, a protein which removes damaged and denaturated proteins from the brain cells.
The body accumulates a lot of sludge, and we need an efficient sludge removal system. When protein sludge accumulates, the gears of the cell cycle can get clogged up. The function of the brain, like many other vital organs, depends upon the timely disposal of abnormal or damaged proteins. Proteasome is our main "cleaning lady" in the cells. Once the proteasome becomes inhibited, ubiquitinated, misfolded, aggregated, and oxidized proteins accumulate in the cells and lead to neurodegeneration and cell death. More
Parkinson´s disease
The ultimate cause, on the atomic level, are toxic free radicals and their toxic metabolites, which damage certain cells in the brain. H2O2 and TPA (tetracanoylphorbolacetate) are such radicals, and they are able to kill brain cells prematurely. Carnosine has been shown to prevent these radicals and it is thus protecting the brain cells (Kang et al. 2002 b).
Lewy particles in the brain of Parkinson patients accumulate a substance called alpha-Synuclein, which accelerates the disease. This substance is produced due to oxidative stress. Carnosine is able to combat both oxidative stress and accumulation of alpha-Synuclein (Kim et al. 2002).
Carnosine is already recommended by some researchers (Nguimfack Mbodie 2002).
MEDLINE data base includes at this writing six documents on the relationship between carnosine and Parkinson´s. If you want to read them, search for "carnosine; Parkinson", and click "go".
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Epilepsy and schizophrenia
These chronic diseases belong to those conditions where oxidative stress and carbonylation damage the brain cells. Carnosine effectively fights these reactions, and is therefore apt as a dietary supplement for these patients (Petroff et al. 2000; 2001, Nguimfack Mbodie 2002).
MEDLINE data base includes at this writing 24 documents on the relationship between carnosine and epilepsy.
If you want to read them, search for "carnosine; epilepsy", and click "go".
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One in 100 persons is schizophrenic |
Autistic spectrum disorders
There has been a major breakthrough by a Chicago neurologist, Dr Michael Chez, in the treatment of autistic Spectrum Disorders (autism and Asperger´s syndrome). Since 2001 he has treated almost 1,000 autistic children with carnosine, and, according to Dr Chez, 80 to 90 per cent improve considerably within eight weeks. Carnosine acts in the frontal part of the brain where it combines with transmitters deep in the brain, says Dr Chez.
Parents with autistic children are saying that supplementation with carnosine helped their kids. Rose Stodola a mother of autistic child said in an TV interview, Almost immediately within the first week I noticed a change. The gym teacher came up to me and said my gosh he's like a different child, added Maureen Sieger. Four-year-old Nicholas Stodola would not talk to anybody. But then he took carnosine and there was a noticeable change.
Dr. Mihael Chez found that kind of change was typical for 80 percent of these and other autistic children. Some jumped eight months in their reading scores and their behavior also changed. Response time, and eye contact and social awareness improved, play skills improved as a general rule, the children´s neurologist says.
What's really exciting is that carnosine works by stabilizing and protecting brain cells and helping patients like Nicholas. And this may be just the beginning. Carnosine may help patients with Alzheimer's, an illness similar to autism and it has already helped some Alzheimer patients. Carnosine's also helped some other children. Dr. Chez says, We've had parents report improved reading skills with dyslexic tendencies...just improved test scores with kids who've had borderline attention disorder. Soon other parents may have the same reaction Nicholas' have. Carnosine and Dr. Chez have given us our son back, says Mrs. Stodola. Some non-autistic adults claim carnosine makes them more alert and improves their memory.
Dr Chez´team has conducted a scientific double-blind study on 31 autistic children. The daily dose of pure L-Carnosine was 400 mg and no adverse side-effects have been observed. The report has been accepted for publication in the Journal of Child Neurology. Read the abstract
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