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CARNOsiNe

Summary overview

expands the
constricted vessels

arteriosclerosis
(prevention of
LDP-cholesterol
oxidation)

increases blood flow


in heart, brain, organs,
and extremities

increases
uptake of
oxygen

cardio-vascular
system
removes pain
in extremities

decreases
blood pressure

recovery of
aging cells
younger and
elastic skin

endurance of
the heart muscle

cells
treatment of neurologic
degenerative diseases

CARNOsiNe

motoric
apparatus

antioxidant

increased
buffering capacity
of skeletal muscles

building
and regeneration
of muscle mass

digestive system

reduces activity
of free radicals

Autism
Spectrum
Disorders
nervous system

removes vessel
disorders of
brain

transfer of impulses
in brain and nerves

antiglycating
effects

removes toxic heavy


metals from body

kidney
disorders
diabetes

improves
memory

catar

Content

Assessment of Carnosine EXTRA product


doc. MUDr. Igo Kajaba, PhD.

Briefly about carnosine

Who is MUDr. Michael Kuera?

Research preview Carnosine


MUDr. Michael Kuera

CARNOsiNe EXTRA

Main components of the preparation are consist of


carnosine - a dipeptide of two amino acids: semi-essential
L-histidine (essential in a period of intensive growth,
pregnancy, conditions of physical and mental stress, and
others), and basic -alanine at protheosynthetic processes
in tissue.
It is also synthesised in human body from the mentioned
amino acids by means of enzyme carnosine- synthetasis,
mainly in brain and muscles, including myocardium, intake
with food as well. It is absorbed only in upper parts of
intestine (jejunum), and then distributed by blood to almost
all organs.
From the broad diapason of health beneficial response
of carnosine, in exact preview listed in the book of MUDr. Michael Kuera, I would like
to mention some from the key ones. Carnosine is the most intensive antioxidant, it
inhibits processes of glykosylation and carbonylation of proteins, and also phospholipids.
Remarkably depresses creation of protein related, advanced end products of glykosylation
AGE, as well as the unfavourable impact of the final product of lipid peroxidation
malondialdehyde on proteins, and not only in several serious clinical conditions, but also
significantly in prevention of processes of premature aging of organism.
The feature of carnosine to form chelae compounds enables to remove harmful products
of metabolism, as well as toxic effects of heavy metals and other alien substances. In
sum it is to say that based on EBM (Evidence Based Medicine) carnosine has significant
protective effects cardiovascular, cerebronervous, immunomodular, cell protective and
regenerative, antioxidative, antisclerotic, antidiabetic, antimulagnous, and by that also
anticancerous. In no case it is to leave out a reference of carnosine in association with its
valuable sexually stimulating function.
Next components of the product are vitamin E, most efficient antioxidant from the vitamin
group, mainly in interplay with vitamin C, which has to reduce the oxidated form of vitamin
E and thus restore its function.
Coenzyme Q10 represents one of the fundamental substances of the new modern
direction mitochondrial medicine. It is an important component of respiratory chain of
mitochondria, has a key importance at ATP creation in mitochondria, where it participates
and decides on course of energetic metabolism in cells.

Coenzyme Q10 has strong antioxidative features, it neutralizes free oxygen and
other radicals, and similarly as vitamin C it is able to regenerate vitamin E. It shows
antiperoxidative effect with lipids, by which it avoids lipoprotein disorders, and onset and
development of atherosclerotic changes.
It is known that human body is equiped with the ability of its biosynthesis, however
fully functional only up to age of 40. Its biosynthesis is then continually reduced, it is very
low in senior age, and its insufficient content in food there is a risk of initiation of some
or several mitochondrial diseases. Next risk is with persons taking statins. These inhibit
the enzyme HMG-CoA reductase and thus prevent from endogenic cholesterol creation,
however at the same time avoids metabolism of mevalonate, which is precursor of Co Q10,
and therefore by lack of mevalonate is this important metabolite CoQ10 absent, and onset
of various clinical demonstrations of this shortage is threatening. From this results that a
50 year old individual who moreover takes statins must necessarily reach for nutritional
additive with content of CoQ10.
L-carnitin is biologically important, it is contained also in breast milk, and therefore
products of artificial milk nutrition of newborns are enriched with carnitine together with
taurine.
L-carnitin is generously represented in metabolically active organs, mainly in muscles,
where it significantly participates in metabolic processes, mitochondrial -oxidation of
fatty acids with long chain by means of enzyme activity of carnitinpalmitoyl- transpherase
1, as well as at creation of ATP in myocardial mitochondria, which emphasizes the
cardioprotective effect.
In frame of the product complexity it is also completed with an extract from blueberries
and wine grapes, which are known by rich content of beneficial flavonoids, and mainly wine
grape with polyphenolic agent resveratrol.
From the given assessment of nutritional additive it is recommended to approve the
preparations, as well as agree with import, distribution, and sales in chain of pharmacies
and nutritional retails in SR.

Doc. MUDr. Igo Kajaba, PhD.


Lead of the Nutrition screening SZU

Briefly about carnosine

Carnosine (-alanyl-L-histidine) is a dipeptide, naturally found in the body (the body


produces it on its own). It is a natural antioxidant, appears in human body since birth, but
later in time its creation is reduced. It is located in skeletal muscles, brain, and myocardium.
Antioxidative mechanism of carnosine is explained as chelating of metal. Experiments
show that carnosine inhibits oxidation of lipids, which is catalysed by iron, and oxidation
of haemoglobin, which is activated by hydrogen peroxide. Carnosine effectively reduces
activity of singlet oxygen, lipoxygenase, and hydroxylated radicals.
In intestine the carnosine is absorbed by specific active transport system in membranes
of brush edge cells, it enters the blood, and is further transported to kidneys, liver, and
muscles. Absorbed carnosine is used in peripheral tissue, or it is hydrolysed by carnosinase.
Carnosine decreases oxidation of LDL-cholesterol, and chelating of copper ions show
that carnosine could inhibit development of atherosclerosis. As of now it is still unknown
whether the antioxidative effect of carnosine is applicable with regards to malignancies.
Growth of malignant cells was reduced after dispending carnosine at breast carcinoma in
experiment. Lately it was identified that carnosine modulates concentration of intracellular
Ca2+, and therewith the contractibility of myocardium or skeletal muscle. Carnosine is an
important component of skeletal muscles, it concentrated also in fast fibres of type II. It
binds H+, and delays the drop in pH .
Possibilities of usage in clinical medicine at atherosclerosis, cancer, diabetes, and
gastrointestinal disorders result from metabolic features of carnosine. Presence of
carnosine in body assures maximum efficiency in cell multiplication, it protects against
DNA oxidation, and eliminates free radicals, accelerates healing of wounds and joint
tissue, increases sport output, protects brain against plaque creation, which is one of the
reasons of Alzheimers disease, improves ability to think logically, memory, as well as
space thinking, moreover the reaction time was improved, as well as the global speed and
accuracy of data processing in brain.
Carnosine was yet in past used in treatment of muscles, joints, digestive system, in
treatment of diabetes complications, various wounds, in treatment of cataract, kidney
diseases, it was applied to oncologic diseases, Alzheimers disease, but also in body
fitness as such. It is known to protect brain against ravaging impact of aging, as well as to
remove some reversible damages caused by aging.
Activity of carnosine is strengthened by parallel reception of oxidants (e.g. vitamins E, C).

Who is MUDr. Michael Kuera?

Recently, more than than 900 studies have been published


about carnosine. Research is performed by experts in
several countries worldwide. MUDr. Michael Kuera
undoubtedly belongs among these experts. A Czech
internal physician since 1994 cooperating with prof. Dr. R.
M. Baevski (Institute for Bio-medical Problems Academy
of Sciences Russian Federation) in range of application
of cosmic medicine into practice, mostly in the field of
prevention and strengthening adaptation mechanisms
on stress. Research activities of internationally accepted
expert on mitochondrial medicine Dr. Kuera were awarded
in 2000 with IMMA-Prize 2000 for clinically relevant
achievements in this area.

cytoplasm

centriols in
centrosome

nucleolus
nucleus

ribosomes
(small spots)

Golgi apparatus

cytoskeleton

endoplasmatic
reticulum

mitochondria

CARNOsiNe
Research preview

2006, MUDr. Michael Kuera, Karla apka 4, 36 001 Karlovy Vary, Czech republic

1. Preface.
2. Pharmacology and biochemistry.
3. Brief history.
4. Strong antioxidant.
5. Chelatogenous effect.
6. Prevention of glycation.
7. Prevention of carbonylation.
8. Beneficial effect against aging.
9. Carnosine rejuvenates skin.
10. Muscle aging, muscle diseases.
11. Carnosine in sport.
12. Disorders of potency.
13. Cataract.
14. Diabetes and its complications.
15. Cardiovascular diseases.
16. Neurologic and mental disorders carnosine as nerve protection.
Alzheimers disease and mild disorders of perception and cognition (mild cognitive
impairment)
 Parkinsons disease
Epilepsy and schizophrenia
Autistic disorders
Brain vessel disorders, brain vessel events (stroke).
17. Next health beneficial effects.
18. Carnosine for longevity.
19. Carnosine as drug and nutrition additive.
20. Posology.
21. Conclusion.
22. References.

1. Preface.

Increasing attention and interest in the recent years is dedicated to phenomenal features
of carnosine, which is considered a substance of the century, and it is assumed to become
a fundamental daily medicine for people of all ages, particularly those who reached 40
years of age and above. Research projects concerning carnosine are conducted in the
US, Australia, the UK, Japan, Scandinavia, Russia and China, and it is recommended by
specialists dealing with aging as a significant and valuable nutrition additive. Carnosine
is examined by top scientists (e.g. Dr. Bruce Ames and his team from UCLA Berkley.
Nobody suspects his high expertise in molecular biology).
Laboratory research in field of cellular senescence (aging) i.e. end of life cycle of two
dividing cells reports that the gained facts cannot be random. Carnosine has remarkable
abilities of cell rejuvenation in senescence process, recovers their normal features, and
extends their lifetime. How can carnosine rejuvenate the cells? Not all questions are
answered so far, but features of carnosine point to key mechanisms of cell and tissue
aging protects against shortening of telomeres and against damaging DNA at cell
dividing.
Later on a list of wholesome impacts on organism was proven. Mechanisms of these
impacts are characterized by following processes:
Physiologic (normal) concentration (20-30 M/l) in standard media in- vitro extend
lifetime of human fibroblasts, and strongly reduce their aging performance.
Carnosine significantly improved the image of laboratory animals, and prolonged their
life. Carnosine could be very useful at the following disorders associated with age:
n eurologic degenerative disorders (Alzheimers and Parkinsons disease, epilepsy,
depressive disorders, schizophrenia, mild cognitive impairment, dementia, various
aetiology, conditions after brain vessel events)
range of autistic diseases (Asperger syndrome, ADHD, dyslexia a dyspraxia, Tourett
syndrome, etc.)
general disorders of cell aging
cross-linking of eye lens, cataract
cross-linking of skin collagen (skin aging)
formation of AGES (Advanced Glycation End Products), i.e. advanced terminal products
of protein glycation
conditions of accumulation of damaged proteins
muscle dystrophy
cardiovascular diseases
brain vessel disorder
diabetes and its complications
Carnosine is as a multifunctional nutrition additive relatively new. It is physiologic and 100
% natural super antioxidant with a spectrum of biologic functions (apart from features listed
above):
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has universal and multilateral antioxidative activity


supports muscle vitality
increases muscle power and endurance
accelerates recovery after sprinting
reduces cell damages caused by alcohol
acts as impulse transferring agent in brain and nerves

2. Pharmacology and biochemistry. Biologic effect.

Carnosine is 100 % natural substance, a so-called dipeptide created by two amino acids
(-Alanyl-L-histidine). It is often called a neuropeptide because of its protective action in
brain. It is commonly found in the body. Based on new trials its highest concentration is
in skeletal muscles, heart, cerebellum and brain. Homocarnosine exists only in brain
and cerebellum. Was not detected in blood plasma, liver, kidneys and lungs. Muscles
contain around 20 mol/g dry
(The more carnosine is contained in meet, the more is the shelf life extended because carnosine as a highly efficient antioxidant prevents
its spoiling)

Fig. 1. Chemical formula L Carnosine


(NH2CH2CH2CONHCH (C4H5N2) CO2H)

COOH
CH2

HN

CH

O
NH

CH2
CH2

NH2

Carnosine acts more effectively with other biologic antioxidants, e.g. vitamins C and E, zinc
and selenium, and reduces its consumption in tissues. It is created in the body from amino
acids alanine and histidine via enzyme carnosine-synthetasis. This reaction runs mainly
in brain and muscles. Other group of enzymes called dipeptidases or carnosinases viceversa dissociate carnosine in blood and other tissues. Many scientists presume and their
trials prove that some positive features of carnosine are just caused by these reactions,
breakdown of carnosine at the rise of alanine and histidine, so the degradation has in this
case a positive nature.

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Meat is the main external supplier of carnosine. Absorption of carnosine from food is
30-70 % (depending on the content of other amino acids in food), but in cases of
intake of pure carnosine, its absorption is more than 70 %. Almost all carnosine is
absorbed in upper parts of intestine (in jejunum, not ileum). It is then carried by blood
directly to muscles, heart, brain, and some other organs. Human plasma does not
contain measurable amount of carnosine, therefore blood tests cannot serve as a test of
its eventual deficiency (lack) on a contrary with horses, where plasma contains more
than 100 mol/l. Content of carnosine in plasma is however increased at muscle
injuries: then the content of carnosine in plasma may serve as a detector of muscle
injuries.
Biologic functions of carnosine are mainly:
buffering effect for lactic acid maintenance of pH (= acidity) in muscles at burden
chelating effect for heavy metals (in particular copper and zinc)
removing (scavenging) effect for free radicals, strong antioxidant
removing effect for active molecules of sugar = prevention of glycation
prevention of protein carbonylation = so-called carnosinylation (glycation and
carbonylation processes typical for protein aging)
separation of aldehydes (aldehyde-sequestring)
preventive effect on modification of bio macromolecules, i.e. maintenance of their natural
functionality yet at condition of oxidative stress (i.e. at condition of prevalence of free
radical formation and lack of antioxidative capacity)
function of nerve impulse transmitting agent (neurotransmitter)
protective effect on proteasomes
depression of anti-inflammatory and cancerogenous effect of cytokine IL-8

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Finally, carnosine is remover of aldehydes and is able to eliminate terminal harmful


waste products of metabolism, such as degradative parts of proteins (damaged chains
of proteins, sugar and phospholipids), while at the same time acts as key substance for
creation of new more resistant structures. As a nutrition additive carnosine is a possible
modulator of diabetic complications, atherosclerosis, Alzheimers and Parkinsons
diseases, epilepsy, autism, dyslexia, schizophrenia and similar syndromes. Copper
and zinc are released during normal synaptic activity.
In presence of slightly acidic environment characteristic for Alzheimers disease these
metals are reduced into their ionized forms and so become toxic for the nervous
system. Research has proven that carnosine neutralizes (with its buffering effect) toxicity
of copper and zinc in brain.
Further on it was proven in vitro that carnosine depresses nonenzymatic glykosylation
and formation of cross linked proteins, caused by reactive aldehydes, aldose and
ketose, some trioselike intermediary products and malondialdehyde (MDA=product of
lipid peroxidation, i.e.. product, arising under influence of oxygen radicals on fatty
substances). Carnosine depresses formation of advanced (protein related) products
of glykosylation (Advanced Glycosylation End products AGEs) induced by MDA.

Also depresses formation of crosslinked DNA proteins, which use to be developed by


acetaldehyde and formaldehyde. Product of lipid peroxidation, MDA, create adducts with
proteins, which are detected at routine tests as prove of protein carbonylation.

3. Brief history.

Carnosine was discovered (and its structure was identified) beginning of 20th century by
a Russian scientist W. S. Gulevi. It was the first and most simple example of biologically
active peptide (dipeptide in our case), which opened a long list of broad spread natural
protein regulators of metabolism. First decades were dedicated to structure studying,
distribution, and features. It was identified that carnosine has direct relations with functions
of triggering tissues such as muscles and brain. In 1953, next Russian scientist S. E.
Severin, proved that carnosine effectively balances pH (acting as a buffer), buffering
the lactic acid produced in working muscles, and that supplying carnosine increases
the contractility of the muscles and their resistance against tiredness. Working
muscle accumulates lactic acid as its own product, pH is dropping (i.e. acidity grows),
which is the main cause of muscle tiredness. When carnosine is administered, the muscle
recovers almost immediately, and keeps working as if was never exhausted. This process
of rapid recovery of muscles caused by carnosine is known as so called Severn
phenomenon.
Everybody with certain experience with sports knows by sure the meaning of physical
exhaustion, and a certainly understands how tremendous importance can a carnosine
supplementation bring to sport activities. Scientific interest in this extraordinary, absolutely
nontoxic substance has grown in the last years in particular after dramatic Australian
and British discoveries on carnosine effect in aging process. Then the scientific work of
Dr. Michael Chez team in 2002 in US was well surprising, as their report on dramatic
improvement in autistic kids after carnosine was published. There is more than 900
carnosine trials published in MEDLINE database recently.

4. Strong antioxidant.

Carnosine is an antioxidant, stabilising and protecting cell membranes. Specifically


as a water soluble antioxidant it prevents lipid peroxidation inside cell (double layer)
membrane. Many antioxidants (as vitamin C and E) protect the tissues before entering
them, but they possess minor effect, when this first line protection is overridden. Free
radicals then cause so-called oxidative stress of organism. Carnosine reacts generally
with all reactive forms of oxygen (Reactive Oxygen Species ROS = free oxygen radicals),
and prevents from development of oxidative stress. Carnosine does not act just
preventively it is also active, when dangerous compounds were already created
by free radicals, such as lipid peroxides and their secondary products. So is the
tissue protected against harmful effect of the substances of the second wave. For
example, a very reactive final product of lipid peroxidation is malondialdehyde (MDA),
dangerous product of free radical reaction, is blocked by carnosine. MDA, in case not
eliminated, may cause damage of lipids, enzymes and DNA, has an important role in

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developing atherosclerosis, inflammatory and degenerative processes of joints,


cataract, and aging processes in general. Carnosine with its reaction and inactivation
of MDA is itself sacrificed in favour of amino acid protection in protein molecules. Ability
to reduce concentration of reactive forms of thiobarbituric acid (Thiobarbituric Acid
Reactive Substances TBARS) is a pretty strange antioxidative feature of carnosine.
Carnosine is a substance protecting and extending functional life cycle of key building
units of the organism proteins, DNA and lipids and can be quite seriously called as
substance of longevity.
Carnosine moreover protects biologic tissue against oxidation, reaction with aldehydic
products of lipid oxidation, which form so-called adducts with DNA, proteins, enzymes
and lipoproteins followed by harmful changes in their biologic acting.
Oxidative stress and stressing injury is enabled by low concentration of carnosine, which
explains the increased fatality of elderly people after stressful events. Therefore sufficient
antioxidative protection is crucial for maintenance of good health, especially at
seniors.
Properties of carnosine against aging not only question of its antioxidative features.
Next mechanism how carnosine protects cells against oxidative stress is its chelategenous
effect, explained by the team of prof. Bruce N. Ames from UCLA, Berkeley. Formation of
chelates with heavy (transitory) metals e.g. such as cadmium, copper, iron, mercury
prevents participation of these metals in the harmful Fenton reaction with peroxides.

5. Chelategenous effect.

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Carnosine has ability to chelate metals.


What does it mean? The term chelate originates from Greek: chele = claw, which
expresses ability of joining, adding some substance (carnosine in this case) with surplus
of metals in tissues and blood. Chelates are substances which could be excreted from
organism through liver and kidneys. Chelate therapy is a traditional classical detox
treatment deployed mainly in occupational medicine. Various chelatogenous medicines
such as penicillamin or EDTA (and others) are used in intravenous form. This treatment
effectively removes heavy metals (e.g. lead) from the body. Chelate treatment is also used
as complementary at many other diseases (not only disorders caused by poisoning with
heavy metals), because it can bring following beneficial effects:
e xpands the constricted vessels
s uppresses increased blood pressure
r educes activity of free radicals
increases oxygen uptake in cells
r emoves toxic heavy metals from organism
improves memory
r emoves pain in extremities
increases vessel elasticity
increased blood flow to heart, brain, organs, and extremities
increases enzymatic activity

In relation with vaccination usage of carnosine could be crucial, as carnosine removes


organic compounds of mercury (thiomersal or thimerosal) from the child body. These
organic compounds of mercury are part of several vaccines as antimicrobial preservants
despite the fact they have been indicated as toxic substances for central nervous system
since 1930. Thus it is suitable for every vaccinated person, no matter if child or adult,
to take carnosine as a prophylactic measure aiming to remove thiomersal as soon as
possible.

Chelate therapy by means of EDTA used to be quite a popular method of treating atherosclerosis EDTA was deployed to remove calcium
from the walls of sclerotic vessels with aim to restore their elasticity. This therapy was however very expensive and time consuming, because
EDTA was administered intravenously with one session lasting around 3 hours, and the course demanded 10 to 20 sessions to achieve the
desired effect..

Carnosine as a nutrition additive proves the same chelatogenous effect as EDTA,


and offers inexpensive, oral chelatetherapy. It is able to chelate prooxidative metals
like copper, zinc, iron and other toxic metals arsenic, lead, mercury, cadmium, and
nickel.

6. Prevention of glycation (glycosylation).

All the diabetics certainly know what HbA1c is. It is glycosylated haemoglobin, which
offers quite good information on glycaemia in the course of last months. Latest research
shows that the most important effects of carnosine are probably the antiglycating ones.
What is glycation? Every second in the whole body a process called glycation
(glycosylation) takes place. This reaction could be described as formation of a bound
of protein molecule with molecule of sugar (glucose) followed by the creation of
damaged, non-functional structures.
Process of glycation alters the structure of protein, and suppresses the biologic activity
of this protein. Glycated proteins accumulated in the touched tissues are reliable indicators
of disorders. Many diseases associated with higher age, such as atherosclerosis, cataract,
and some neurologic disorders are at least partly attributed to glycation.
Carnosine, which prevents glycation, plays an important role also in removal of glycated
proteins. So called carnosynilation (process, where carnosine is bound to denatured
molecules) enables removal of glycated proteins from cells.
Glycation, in biochemistry known as Maillard reaction, runs between proteins and
glucose, is considered as important aging factor and probably also a factor in malignant
tumours, including complications caused by diabetes. Glucose is a fuel for glycation,
malicious binding of protein/glucose, followed by creation of free radicals, ends up in AGEs
(Advanced Glycation Endproducts).
When the AGEs are formed, they react with neighbour proteins and build pathologic
cross-links, which cause hardening, stiffness of the tissue. It is an object of ongoing
discussion, that in fact no other molecule has such important potential toxic impact on

15

proteins as AGEs. Diabetics build enormous amount of AGEs considerably earlier in


life course than healthy individuals this process totally disrupts normal organ functions,
which are dependent on flexibility. It was proven that just glycation processes are those
resulting in hardening arteries of diabetics.
AGEs launch a full cascade of destructive processes when bound to cell binding
structures. One of the results is 50x higher formation of free radicals. So diabetes in fact
a disease of accelerated aging becomes a source for AGEs, and arteries, eye lens and
retina, peripheral nerves and kidneys are specifically attacked. Inhibiting glycation then
means that damage of kidneys followed by inflammatory and degenerative changes are
softened. Rats with diabetes not treated with glycation inhibitors, showed double damage
of kidney glomerules caused by AGEs in comparison with control group treated with these
inhibitors.
Cataract next complication of diabetes is also result of glycation process. Inhibitors
of glycation, as carnosine and calciumpyruvat, protect against this damage.
Supplying inhibitors of glycation may allow preventing many deviations accompanying
the aging process. Since carnosine structurally contains sites that are attacked by glycation,
it must be sacrificed to protect the aim. Carnosine also supports the protheolytic paths, i.e.
removal of damaged and unnecessary, often harmful proteins.
Therefore carnosine with anti-glycating effect could be useful in prevention and
treatment of diabetic complications like cataract, neuropathy, atherosclerosis, and
kidney failure.
It may also be useful for everyone of us, despite not being attacked by AGEs so
rapidly as the diabetics are.

7. Prevention of carbonylation.

16

Why are old people, and animals, visually different to the young?
It is given mainly by the changes in body proteins. Proteins are substances most important
for daily functioning living organisms. Therefore their modification has dramatic impact
on function of organism and its image. A number of research tasks of the last decade
have been focused on investigating protein modifications as most important reason of
aging and degenerative diseases. These modifications (deterioration, change of structure,
etc.) of proteins are consequences of oxidation (thus impact of free radicals), and similar
following processes such as glycation.
Our body consists mainly of proteins. However the antioxidative system, and other
protective processes cannot completely protect the proteins, these tempt to undergo
destructive changes in the course of life, in particular by means of free radicals, glycation,
and also by process named carbonylation. In another words, carbonyl groups (> C = O)
are bound to protein molecule (alternatively to phospholipids) resulting in disrupting
protein structure in process named proteolysis. Since protein carbonylation stands
before loss of cell membrane integrity, it is associated with toxic processes leading to cell
aging, and cell death.
Majority of protein modification processes, their de facto denaturation, and
proteolysis (break down) are caused by oxidation (free radicals), carbonylation,

building cross links, glycation, and formation of advanced final glycation products
(AGEs) as described above. These processes do not show up only in general changes
associated with aging, but are typical for changes that manifest themselves with skin
aging, development of cataract, and degenerative processes of nerve cells (e.g. loss of
memory, dementia, etc.).
A number of scientific trials point to carnosine as effective substance acting against
all mentioned possesses of protein denaturation. Carnosine reacts with
carbonyl group and forms so called protein-carbonyl-carnosine adduct, and thereby
protects this protein, and on the top of it turns this process into recovery of disrupted
protein structure.
How is carnosine capable of causing it? It simply restores normal management of cell
cycles. For better understanding of how carnosine works it is possible to imagine the
following: every engine needs regular oil change, because during its operation various
microscopic and larger particles caused by abrasion appear. Oil contains detergents,
which keep the particles resolved. Once the detergents are spent, the waste particles
grow bigger, and damage the smooth internal surface, the engine looses power up to
total failure. A body also needs an effective method of removing metabolic waste, mainly
remains of destroyed protein structures. This protein mud piles up if not removed in
the cell and causes that functional life cycles of this cell are slowed down until they
come to a full stop. This could also disturb effective cell division and possibly even
more significantly allows next reproduction of this disrupted abnormal cell. This leads
to increased chromosomal instability, resulting in degenerative changes, or malignant
tumours. Another possible outcome is the development of cell senescence (aging), when
the worn cell stops its division. Carbonylation of proteins becomes the main condition
of cell life termination. Carnosine represents the main factor of sustainability and
safeguarding intact healthy proteins, their functionality, and early replacement. Carnosine
represents a substance that significantly exceeds traditional antioxidants such as vitamin
E or selenium, which are not so effective as we had hoped in the past. Traditional
antioxidants play certainly an important role in various processes of removing
free radicals, but have no effect on carbonylation, and glycation. There is no doubt
that the influence of antioxidants represent a key process of biochemical reactions
protecting against damaging biologic structures by free radicals. To expect that traditional
antioxidants shall protect against savage processes of glycation and carbonylation is the
same as building a house with a screwdriver a basic tool but totally unable to substitute
other important tools.
Carnosine is pure natural, versatile, multipurpose, and universal means of protein
protection which was developed by evolution to manage numerous factors cooperating
at protein degradation processes. Chemical side reactions which disturb biologic
structures and functions in the course of aging are outcome of toxic impacts of many own
and fundamental elements of chemical composition of organism oxygen, sugar, fats, and
essential metals. Organisms cannot exist without these biochemical elements, and recent
science about nutrition provides us with information to better understand their side effects,
and have better control. Proteins are not the only ones denaturised by carbonylation

17

phospholipids are carbonylated, too. Carbonylation of phospholipids causes damage


mainly of central, and peripheral nervous system, which leads memory and perception
disorders. Carnosine in this case is able to protect phospholipids against carbonylation,
possibly regenerate them (as proteins do), so it is not incidental that this miraculous
dipeptide is unbelievably important neuroprotectant (safeguards neural cells) see later
in text.
In sports and bodybuilding, carnosine participates in detoxicating processes of removing
harmful reactive aldehydes, which are created by peroxidation of lipids in skeletal muscles
at endurance performances (sportsmen). Carnosine protects muscles against damaging,
increases muscle power, endurance, and significantly accelerates processes of recovery
after extreme excercises, see next chapters.

8. Beneficial effect against aging.

Carnosine has many literally rejuvenating wholesome effects it is to admire how such
a small molecule of dipeptide may have such a tremendous effect in sense of rejuvenating
organism. Carnosine has extraordinary ability to rejuvenate old and aging cells and
turn the fully functional and healthy. It was assumed that old cells are not able to be
rejuvenated before the trial results on carnosine effect were known. Recent knowledge
shows that carnosine prolongs the period between two cell divisions and at the same
time increases the number of divisions. It means that the cell life is significantly extended,
whereas the relation is direct: the more carnosine the longer intervals between divisions,
and more divisions are in place.
Carnosine extends the average life of fibroblasts in culture, destroys their
transformed (mutated) forms, protects against aldehydes and formation of
-amyloide fragments (characteristic for Alzheimers disease), and against creation
of -synukleinu (Parkinsons disease). At the same time suppresses, at least in vitro,
glycation of proteins, and formation of dangerous cross links DNA/protein.
Recent research proves that patients taking carnosine quite objectively after some
time (some 6 to 12 months) appear younger than before use. This supports findings from
in vitro experimental trials and experimental works confirming that carnosine is able to
rejuvenate cells in cultures, and also in vivo, performed on laboratory animals where
carnosine suppresses visible signs of aging. During these trials carnosine significantly
delayed development of skin ulceration in eye area, vertebral lordokyphosis, typical
manifestation of old age. Moreover mice suplemented with carnosine not only
looked younger than mice in control group (i.e. without carnosine), but achieved
average life extension by 20 %. As a curiosity a rumor circulates that Boris Yeltsin
had been taking the Russian supervitamin, i.e. carnosine for some time, so that he
looked 10 years younger.

9. Carnosine rejuvenates skin.


18

Normal cells are aging also in their replication abilities, it is the number of division repetition.
Shortening of DNA telomeres occurs at every division (telomere = marginal DNA complex
with protein protecting the chromosome edges). This DNA shortening after each division

causes creation of a so called DNA damage signal in a certain moment, and p53 is
activated. Some chemotherapeutics induce such of rapid cell aging in malignant, and
healthy cells. Carnosine on the contrary has a very effective impact on reverting signs of
aging in skin cells (fibroblasts) already in process of aging, and restore their functionality
together with extension of their lifetime. These functions are typical for effect of carnosine
to prevent all forms of harmful changes in protein and phospholipid molecules, and also
to significantly limit cutting of DNA telomeres, i.e. to prevent damage to the DNA. Limited
number of cell divisions is called Hayflick limit. It is the maximum number of cell divisions
before its destruction. Hayflick limit refers to the mortality of cells. Majority of the cells in
fact regenerate in division into two daughter cells. Since 1961 Dr. Leonard Hayflick proved
that cells can achieve a limited number of divisions, and later lose their dividing ability.
His well known experiments demonstrated that cultures of human fibroblasts (cells of joint
tissue) are able to divide maximum 60 to 80 times, while fibroblasts of young people were
able to divide 30 to 40 times, and fibroblasts of older ones only 10 to 20 times. When
cells achieve this Hayflick limit, the twilight called cell senescence arrives, i.e. aging.
Cells in senescence are still alive, but they do not divide anymore, and are damaged in
structure and functionality. Human fibroblasts are very suitable for performing cultivation
and experimental trials in laboratories. Fibroblast cultures in senescence cannot be
exchanged with young one because they are quite uniform and create groups of parallel
fibres. Senescent fibroblasts on a contrary are granular, are variable in size, do not group,
and their fibres are irregular and differ in length they lose their ability to organise regular
forms. These important features of old cells are called as senescent phenotype (young
cells then represent a juvenile phenotype).
Remarkable set of experiments was performed by Australian scientists under lead of
Dr. McFarland, who has proven that carnosine rejuvenates cells heading to senescence.
The most exciting fact in these experiments is that theyve proven the ability of carnosine
to reverse signs of aging. Namely when the aging cells were put in a culture enriched with
carnosine, they showed not only phenotype change from senescent to juvenile, but also
increased ability to divide. They again exhibited ability of organisation, became uniform,
and built organised fibre groups. Once they were moved back in the culture without
carnosine the signs of senescence returned rapidly. The same cells were again put into
the carnosine culture, and again they showed juvenile phenotype. This was repeated with
the same cells many times, and in medium with carnosine the phenotype was changed to
juvenile, in culture without carnosine the phenotype was senescent. Moreover, carnosine
significantly extended lifetime of old cells. These experiments were later confirmed also by
British scientists under the lead of Dr. Alan Hipkiss, mainly the ability to prolong the lifetime
of human fibroblasts.
Carnosine delays processes of aging in cultures of human fibroblasts, and is able to
change senescent phenotype to a juvenile phenotype. Anyhow the positive properties
of antioxidants in removal of free radicals may be, they never prove features
against aging process like carnosine does. These are just associated, next features
of carnosine, its attributes in process of senescence. It is especially notable that
carnosine is able to react with carbonyl groups to form carnosinylated polypeptides

19

(adducts) which suppress aging process, and reduce formation of protein damages
typical for these processes.
Revitalising effect of carnosine on fibroblasts is also explaining the reason of significantly
improved heeling of wounds after surgical interventions.
What in fact causes wrinkles on the skin? Aging (senescent) skin cells, keratinocytes
and fibroblasts after protein changes start to behave abnormally, and accumulate in
human skin in the course of time. They produce more metal-proteinase-like enzymes,
which damage proteins in surrounding matrix (extracellular mass where cells, lymphatic
nodes, vessels, and other skin structures are placed).
They also produce adhesive molecules which cause thickening of vessel walls and their
stiffness (arteriosclerosis). Senescent cells produce more other degradative enzymes and
anti-inflammatory cytokines with action in distant areas of the body (transport by blood).
That way can a relatively small amount of senescent cell cause relatively extensive
changes in function, and integrity of the skin. Senescent cells accumulate in all organs and
tissues where they withstand so called apoptosis (programmed cell death), and invoke
degenerative aging processes. Moreover: disruption of microscopic environment by the
accumulated senescent cells may be the reason behing increased incidence of malignant
diseases in the elderly.

10. Muscle aging, muscle disorders.

20

From 20 to 70 years of age the muscle mass drops by 20 %, equally does the power and
endurance, so the total reduction of muscle efficiency is higher than 20 % and approaches
40 %.
Concentration of carnosine and its antioxidative effect drops to the half of original values
during this period. This reduction of carnosine content in muscles is most probably also
influenced by reduction of muscle mass, power, and endurance due to age.
Active, strong so called fast muscle fibres contain big amount of carnosine, while the
weak and atrophic ones contain significantly less carnosine. Russian scientist Severin
proved already in the fifties that supplying carnosine to the liquid where incubated isolated
exhausted muscles were kept caused almost immediately recovery of the full muscle
energy.
Australian team of Dr. MacFarlane has recently proven that supplying carnosine
increases power and endurance of tired muscles. It is interesting that supplementation
with carnosine is directly related to the final effect on the muscle: the more carnosine is
supplied, the higher its content in muscles and consequently the power and endurance
increases comparably. Role of carnosine was also scientifically investigated in various
neuro-muscular disorders. Results of those trials recommend supplementation of
carnosine in these disorders. Obviously curing of these severe diseases is not expected,
but oxidative stress accompanying these diseases can be reduced, contractility of
muscles can be increased, and power and endurance can be donated. Muscles of
patients with Duchenne muscle dystrophy contain just half of the carnosine levels
compared to the muscles of healthy people, so the supplementation with carnosine
is plausible.

Carnosine plays an important role in the following neurological disorders:


ALS (amyotrophic lateral sclerosis)
Duchenne muscle dystrophy
FSH muscle dystrophy
Myasthenia gravis
Polymyositis
Muscle disorders induced by drugs (e.g. statins, cholesterol reducing medication)
Mitochondrial myopathy (late stages)

11. Carnosine in sport.

Russian scientist E. S. Severin proved already in 1953 that carnosine significantly


contributes To physio-chemical balancing of acidity (buffering) in skeletal muscles by keeping
acidobasic balance during the intensive muscle work where surpluses of H+ produced in
relation with accumulation of lactic acid take place whereas significant increase of acidity
in muscles causing muscle tiredness, reduced power and endurance appears together
with regeneration slowdown. Carnosine represents 30 % of total buffering capacity of
organism. Recent studies confirmed that increased concentration of carnosine leads to
increased buffering capacity for H+, i.e. carnosine regulates (buffers) intracellular acidity
(pH). It is important that carnosine has this feature also supplied before exercise.
It is generally known that accumulation of lactic acid in working muscle causes
decrease of pH, i.e. increase of acidity which results in muscle tiredness, and even
exhaustion.
Reduction of carnosine concentration in the course of life leads to suppression of
muscle power and endurance. Supplementation with carnosine leads to its increased
concentration, thus recovery and increase of power, resistance, endurance, and
accelerated regeneration.
Carnosine also helps the function of so called calcium pump in sarcoplasmatic
reticulum of muscle cells, and maintains the calcium channels opened. The pump stops
working at lack of carnosine, calcium channels are closing as a consequence of acidity
increase, lipid peroxidation increase, and accumulation of malondialdehydes (MDA).
Carnosine prevents development of these harmful reactions, and represents an ideal
physiologic additive in sport. Carnosine is not declared as a doping substance.
In sport and body-building, carnosine is participating on detoxication of reactive
aldehydes formed by lipid peroxidation during the muscle work. That way carnosine
protects muscles against damaging, increases their power, resistance, endurance,
and accelerates regeneration this was confirmed by a proven number of trials. Above
mentioned features of carnosine were also investigated from the view of quantity that is
able to provide those features. Studies proved that minimum quantity is 2.5 mM to stop
lipid peroxidation, and 1.0 mM to suppress carbonylation. These concentrations are
reachable at carnosine supplementation after several months (even after 13 months
according to one trial). Food containing 1.8 % carnosine provided concentration growth
in muscles up to 5 times yet after 8 weeks. Carnosine represents an ideal supply for
athletes.

21

12. Disorder of potency.

Production of nitrate oxide (NO) in penis is a precondition to initiate and maintain erection.
Carnosine is a natural source of NO, in another words, body creates NO from carnosine.
Carnosine supplementation automatically improves potency.

13. Cataract.

Carnosine not only suppresses AGEs one of the main processes leading to cataract,
but also protects normal proteins against toxic effect of AGEs already developed. This
knowledge is rather new, since 2000, when papers from Kings College, University of London
(C. Brownson, A. R. Hipkiss et al.) on effects of carnosine were published. Experiments
were based on the following: glycated ovalbumine was created (proteinof egg white was
impaired by effect of a known glycating substance, methylglyoxale). This way impaired
ovalbumine was mixed with cristaline, eye lens protein, and caused formation of
cross-linings in cristaline, and thereafter its opacity. Carnosine not only prevented
cristaline from impairment, but also recovered its structure, and transparency.
Next studies confirmed positive effects of carnosine on developed glaucoma, and its
prevention. This finding is very important also for patients suffering with Alzheimers and
Parkinsons disease, where glaucoma has an increased incidence. Effect of carnosine
eye drops in delaying of aging process of eye and sight, has been definitely proven,
and it has been found to be almost 100 % effective in cases of primary senile cataract,
and in 80 % cases of developed senile cataract. These drops penetrate aqueous and
lipid eye parts, where carnosine acts preventively and correctively on light induced DNA.
Carnosine drops are administered regularly as a medication for several eye diseases in
some countries.

14 . Diabetes and its complications.

22

Diabetics excrete increased quantity of sugar and other substances such as proteins,
amino acids(arginine, carnosine, taurine, etc.), and magnesium with urine. Obviously they
impoverish their body with those necessary substances. Diabetes intensifies processes
of glycation concomitantly with growing deficiency of carnosine, which is one of the
reasons (not the only one however) for arteries of diabetics to be more prone to thickening
of their walls, thus developing atherosclerosis. Incidence of atherosclerosis in diabetics
is three times higher (including incidence of myocardial infarction, and cerebrovascular
disorders) as in nondiabetics.
Carnosine is a substance that controls levels of blood sugar via H3-receptors of
autonomous (vegetative) nervous system. Tests on animals have proven that pregnant
rats with the lack of carnosine have significantly higher risk to bear diabetic offspring. This
is explained by the effect of carnosine which improves glucose tolerance of the fetus.
This way carnosine can be a valuable additive for diabetic mothers as it reduces risk of
their children falling ill with diabetes.
Carnosine is suitable for all types of diabeties because it reduces the risk of diabetic
complication development, i.e. heart disease, cerebrovascular events, atherosclerosis,
kidney damages, and eye complications.

15. Cardiovascular disorders.

Healthy myocardium naturally contains a certain amount of carnosine.


Supplementation of carnosine however increases very significantly (even by 30 %)
power and endurance of the heart muscle. Loss of contractility of myocardial cells is
a common reason of death caused by damages from ischemic heart disease. Based
on recent pharmacologic trials carnosine improves contractility of myocardium even
in the course of ischemia equally well as verapamil (medicine - blocker of calcium
channels), often prescribed as a medicine of heart diseases. This way carnosine opens
brand new horizons in treatment of heart insufficiency. beneficial effects of carnosine on
cardiovascular disorders can be summarized based on performed trials:
increased power of contractions of myocardium
reduced high blood pressure
protection against oxygen deficit (hypoxia, ischemia) in tissues at ischemic heart disease
prevention of LDL-cholesterol oxidation, and atherosclerosis development
Carnosine can be broadly used to treat all forms of reduced heart pumping efficiency.
Moreover, carnosine reduces level of leptine, hormone of obesity. This hormone is
several times higher in blood of diabetics, and lifts the blood pressure, too.
Interesting experiments were performed with aim to explain the effect of carnosine on rats
with programmed hypoxia (lack of oxygen), i.e. exposed to environment with such oxygen
deficiency as to cause inability to move. Revitalisation was performed by adding oxygen to
their environment. Rats treated with carnosine were able to get up after 4,3 minutes,
untreated ones only after 6,3 minutes, which is a statistically significant difference.
Next study was performed with animals with artificially induced brain stroke. Carnosine
indicated significant neuroprotective effects (protection of nerve cells against damage)
in ischemized brains (brain with insufficient oxygen supply). Rats supplemented with
carnosine had normal ECG readings, less accumulated lactic acid (general indicator of
damage severity), and demonstrated better parameters of brain blood circulation.
Finally it is possible to state that carnosine is an outstanding nutrition additive in
prevention and treatment of almost all cardiovascular disorders.

16. Neurologic and mental disorders carnosines role in nerve


protection.

Alzheimers disease and mild cognitive impairment


Parkinsons disease
Epilepsy and schizophrenia
Autistic disorders
Vascular brain disorder, vascular brain events (stroke)
Carnosine is a versatile neuroprotectant. Evolution ensured that healthy and young
nerve cells of brain contain sufficient amount of carnosine for protection of very valuable
cells against damage, and degenerative changes. Protective features refer mainly to
antioxidative effects of carnosine, and prevention of glycation and carbonylation, as
mentioned above. Moreover, carnosine protects proteasoma, which plays a central role

23

24

in removal of harmful carbonylated proteins. Carnosine simply stops the process of protein
deformation, and paves the way to prevention, and delays the progression of Alzheimers
disease and next types of dementia, and mild cognitive impairment.
At chronic disorders of brain, Alzheimers and Parkinsons diseases, epilepsy,
depressive disorders, schizophrenia everywhere oxidative stress is prevailing, and the
above mentioned concomitant harmful degenerative processes are ongoing at these
diseases at an alarming rate. Glycation denaturates proteins and phospholipids followed
by production of AGEs, which are fuel for oxidation of cell membrane lipids.
Oxidative stress increases activity of enzyme phospholipase A2 (PLA2) that disrupts
fatty acids of cell membranes, which causes violation of membrane integrity, and heavy
function failure of cells until death. All these harmful reactions disturb the function of
neurotransmitters at the same time. Carnosine not only reduces the oxidative stress, but
reduces the damage from the following or concomitant processes (glycation, carbonylation,
AGEs). Carnosine also acts directly as a neurotransmitter, anticonvulsive agent,
and chelating substance (binding heavy metals). This way it becomes a versatile
substance protecting against neurologic and mental syndromes and disorders.
Alzheimers disease and MCI - mild cognitive impairment. Alzheimers disease is a
degenerative disease of brain causing progressive memory disturbance and cognitive
abilities.
Disease slowly and mercilessly attacks nerve cells in all parts of brain cortex, and
surrounding structures resulting in the inability of the patient to control emotions,
differentiate errors, mistakes, patterns, coordinate movements, and ability to remember.
Patient in the final stage completely loses memory and all mental functions. Cure has not
yet been found, and medication used currently yields insufficient results.
Apart from the progressive nerve cell destruction it is possible to detect broad spectrum
of other abnormalities in dead patients on Alzheimers disease including extracellular
deposit of amyloide and microscopic bunches of fibres intracelularly inside nerve
cells. Experimental works have found that carnosine is able to reduce or completely avoid
cell damage, where the reason is toxic impact of amyloide, protein typical for Alzheimers
disease. Beta-amyloid reacts with certain RAGE receptors, and causes damage to
nerve cells and brain arteries. Carnosine blocks and inactivates beta-amyloid, and so
protects nerve tissue against dementia developing.
Moreover, carnosine protects brain cells with its neutralizing effect against highly toxic
substance alfa-beta-unsaturated aldehyde of acroleine formed during peroxidation of
multi-unsaturated lipids (PUFA). This substance very likely acts as toxicological second
messenger during oxidative (i.e. free radicals) destruction of cell membranes. Recent
research has found that also toxic unsaturated crotonaldehyde (CA) participates in the
following process of protein and phospholipid destruction (mainly of cell membranes)
by carbonylation influenced by lipid peroxidation. Due to the fact that carnosine fights
all aldehydes, explanation of next action is offered as an important preventive factor of
Alzheimers disease and other diseases associated with oxidative stress.
Carnosine acts preventively also on next mechanisms accompanying Alzheimers
disease. Some studies on this disorder have found increased concentration of zinc

and copper ions in brains of the patients. These ions probably change the chemical
construction of normal beta-amyloide, and are reason of its toxicity. This change demands
slightly acidic environment to make it happen, i.e. to bind the zinc and/or copper ion with
beta-amyloid. These conditions (acidic medium and increased concentration of zinc and
copper ions) are generally present as a part of inflammatory reaction on site of the damage.
Carnosine as an exceptional chelator of zinc and copper (and other metals) is able
to remove these metals from the body (as described above). This may imply another
important function of carnosine in prevention and delay of progress in Alzheimers disease
and other degenerative brain diseases .

Mild cognitive impairment MCI.

This disorder is currently described as transition between healthy aging of cognitive


function and dementia. Studies dealing with the issue of MCI, assume important role
of multiplicity of this disorder together with statement that the role of some causal
processes are underestimated, such as cerebrovascular illness. At such multiplicity
it is very difficult to correctly identify the prevalence, prognosis, and possible benefit
and advantage of treatment. Carnosine with its powerful neuro-protective effect is offered
as an ideal supplement for persons in suspicion on developing MCI or its initial stages.

Parkinsons disease.

Final cause on the atomic level are toxic free radicals and their toxic metabolites, that
destroy certain brain cells. H2 O2 and TCA (tetracanoylphorbolacetate) are such free radicals
and are able to early destroy brain cells. Carnosine is able to avoid formation of these radicals
and therefore protects brain cells against damage. Next, the so called Lewy particle in brain
of Parkinsons patients accumulates a substance called alfa-synuclein, which accelerates
the process of disease. Alfasynuclein is created in oxidative stress and carnosine is able
to reduce the oxidative stress, and accumulation of alfa-synuclein. Therefore carnosine
is already recommended as additional treatment of Parkinsons disease.

Epilepsy and schizophrenia.

These chronic disorders also belong to the big group of diseases, where on damaging of
brain cells oxidative stress and carbonylation is participating. Because carnosine effectively
suppresses both forms of reaction, it becomes a suitable nutrition additive to the treatment of
those patients. Carnosine has important anticonvulsive effect, as it was proved in trials lately.

Vascular brain events.

Laboratory experiments have proven that supplementation with carnosine protects


brain cells against damage from oxygen insufficiency (ischemia which is demonstrated
at or after sudden closure of some brain arteries (stroke, ictus). The result of one of the
trials has found mortality in rats after ischemic stroke as high as 67 % . In the group
treated with carnosine (i.e. supplementation with carnosine had been initiated before
the ictus) the mortality was 30 %. Another trial finished with similar results mortality
after ischemic attack dropped from 55 % to 17 %. Therefore a growing number of

25

researchers share the opinion that carnosine is a beneficial supplement for secondary
prevention of vascular brain events.

Disorders of autistic spectrum.

It was quite an excitement when Dr. Michael Chez, neurologist, published treatment results
of autistic diseases (autism and Aspergers syndrome). Since 2001, he has treated
almost 1 000 autistic children with carnosine. He claims that in 80 to 90 % of cases,
the condition has significantly improved as early as 8 weeks after the start of the
treatment. According to Dr. Chez, carnosine acts in frontal parts of brain where it joins
its effects with effects of neurotransmitters acting in deep parts of the brain. Remarkable
results of this treatment were confirmed by parents of autistic children, even on the first
week after treatment onset. Improvement has been observed not only in communication
area, but also in behaviour and social contacts. Treatment of dyslectics treated by
Dr. Chez also manifested improvement, mainly in the area of reading skills and level
of attention. Beyond the report on treatment of mentioned number of autistic children
Dr. Chez performed a double-blind study with 31 autistic children with similar results. He
administered 400 mg carnosine daily, and no side effects were observed.

17. Further beneficial effects on health.

Historically since 1936, carnosine has been used in treatment and prevention of
stomach ulcers. Recent trials have found that carnosine very significantly suppresses
forming of erosions and ulcerations in stomach and duodenum. Ulcer diseases and nonulcerous digestive disorders (dyspepsia) impact millions of people worldwide. They are the
reason behind the high morbidity and impose great financial expenses on diagnostics
and treatment. One of the primary reasons is the Helicobacter pylori infection, which is
present at nearly 75 % cases of disorders. Most infected are probably the carriers of this
infection on next persons. Second main reason is using of nonsteroid antirheumatics
(NSAID), including aspirin. These medicines suppress activity of cyclooxygenase (COX),
a useful enzyme responsible for keeping integrity of mucosa in upper part of digestive
tract, and for blood flow support to stomach. Despite deployment of modern nonsteroid
antirheumatics with activity mainly against another form of cyclooxygenase (inhibitors
COX-2), which is placed mainly in the joint cartilage, these medicines remain dangerous,
however smaller for digestive tract as far as the ulcerations.
Further beneficial effects of carnosine are:
support of immune system and suppression of inflammatory processes,
significant support of wound healing, and protection against radiation, including
suppressing of post-radiation syndrome,
prevention of malignancies

18. Carnosine for longevity.


26

Quite a broad research documents that carnosine has important anti-aging potential
given its exceptional abilities to protect and extend functional viability of key building

units of organism, i.e. cells, proteins, DNA, and lipids. Carnosine can be quite frankly
called a substance of longevity. And since this substance is safe, naturally occurring in
organism and food, and found to extend life in animals and cultures of human cells, it
becomes the fundamental substance for life extension program.
How does carnosine extend life?
Answer to this question is not fully known, but features of carnosine point to mechanisms of
aging of cells and tissues, and to anti-aging propertiex, which suppress these processes.
Interesting experiments have been carried out by Russian experts by the end of 1990s,
which tested effects of carnosine against aging in mice average life time and signs of
senescence (aging) in mice with accelerated aging process was tested. Half of the mice
were given drinking water with carnosine since second month of life Here carnosine
extended life in average by 20% compared to the control group fed without carnosine.
Moreover, these mice with accelerated aging with average life of 15 months, show signs
of aging in average in10th month. Mice fed with the addition of carnosine were still without
signs of aging in 12th month.
Their fur has shown quite visible signs of youth in this age glossy fur (44 % versus
5 %), a lower occurrence of skin ulceration (typical sign of age in these mice) (14 %
versus 36 %).
Carnosine also significantly reduced occurrence of spinal lordokyphosis (pathologic
spine curving as next aging sign), and skin lesions around eyes, but had no impact
on occurrence of corneal opacity. However the sharpest contrast was observed in
behaviour just 5 % mice without carnosine showed normal behaviour in old age,
compared to 58 % with carnosine.
Biochemical indicators of brain aging were tested as well. Membranes of brain
cells of carnosine mice had statistically significant lower content of malodialdehyde
(MDA), highly toxic product of oxidative (free radicals) damaged membrane lipids.
Activity of monoaminooxidase B was lower by 44 % in carnosine mice, what points
to maintenance of dopamine production (neurotransmitter whose lack leads to
Parkinsons disease). Glutamate bound to its cell receptors double in carnosine mice.
As glutamate is the main excitation transmitter, it can explain normal behaviour of mice
fed with carnosine. This trial has found that carnosine significantly improves signs
of aging given the physiologic health, behaviour, and brain biochemical indicators,
including life extension in genetically altered mice with accelerated aging. Authors of this
trial modestly conclude that mice fed with carnosine could be characterized as being more
resistant to the development of signs of aging.

19. Carnosine as a medicine and a nutrition additive.

For many years, this remarkable substance has beeb recommended with a broad range
of treatment options. For example in 1935 as medicament for polyarthritis, in1936 to treat
ulcer diseases of stomach and duodenum. Some recent studies recommend combination
of zinc and carnosine, which has important protective effect against various mucosa
triggering substances, and shows healing effect even with existing ulcers of digestive tract.

27

Carnosine has a strange property, it is able to regulate cell and enzymatic processes, when
out of order: when the processes are in excess, they are suppressed (down- regulation),
when they are insufficient, they are supported (up-regulation) e.g. carnosine represents
antiagregating features (reduction of increased blood clotting, i.e. risk of thromboembolic
events, blood dilution) in patients with increased clotting, vice-versa increases
aggregating features of thrombocytes in people with increased bleeding. Carnosine has
protective and stabilizing effect on cell membranes, increases their resistance and period
of survival in adverse conditions, and does offer possibility of medicinal use in chemically
induced haemolytic anaemia.

20. Posology.

It has been found that doses from 50 mg carnosine effectively reduce concentration of
malodialdehyde (MDA sign of oxidative stress) excreted by urine. Currently recommended
dosage:
for preventive purposes, and as component of anti-senescence programs (i.e. against
aging) suitable doses are 100 200 mg/day, without interruption, permanently
as additional treatment of chronic conditions like autism, muscle dystrophy, etc. 300
800 mg/day
1 500 2 000 mg daily are not recommended despite they do not prove adverse effects
nor complications, from the reason that those mega doses do not significantly increase
its favourable effects. Sportsmen are exception, for those are mega doses very useful
particularly during limited period of sporting event.

21. Conclusion.

28

Effects of carnosine result from previous text. Several most important properties are
mentioned:
safe, naturally occurring in body and food
anti-inflammatory and anticancer effect
universal antioxidant and aldehyde sweeper
absorbs toxic effects of hydroxyl, superoxyl and peroxyl radicals
perfect protector of chromosomes (DNA) against damage by free radicals
suppresses effective lipid peroxidation
significantly absorbs (natural way) glycation processes
inhibitor of AGEs formation, protects proteins against damage by AGEs
suppresses formation of protein cross-linking
represents multifunctional protection of proteins and phospholipids
protects proteins against damage by carbonylation
inhibits processes of damaging healthy proteins by their denaturised forms
helps recycling damaged proteins by protecting proteasoma
helps to preserve normal protein recovery
significantly positive effect in autistic diseases
protects brain cells against damage
protects brain proteins and biochemical parameters

acts as neurotransmitter
rejuvenates cultivated human cells in senescence
extends life time
protects against toxic impact of heavy metals, chelates zinc and copper, chelates of zinc
and copper created by carnosine then resolve plaques at Alzheimers disease (positive
effect of these chelates)
suppresses formation of cross-linking of beta-amyloide at Alzheimers disease and their
penetration into plaques.

References
Carnosine references
Last updated 14.06.2005
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Effective dipeptide,
For a more colorfull life.

Unique composition
of Carnosine EXTRA assures:
longer action of carnosine
in organism (8 to 12 hours),
g uarranteed action of carnosine
in cell mitochondria,
formation of healthy cells
and suspension of damaged cells.

1 capsule contains:
carnosine
d-alfa-tocoferyl succinate,
corresponding to 16 mg vitamin E
L-carnitine
coensyme Q10
extrakt from blueberries
extrakt from wine grapes

% RDD
125 mg
20 mg
13,6 mg
20 mg
20 mg
20 mg

130 %

33,33 %

% RDD = % recommended daily dose

Ordering is simple:
c all 0850 555 001
 ail to objednavky@carnomed.sk
m
visit our internet shop www.shop.carnomed.sk

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39

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t

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