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Carnosine - The New Anti-Aging Supplement
by Marios Kyriazis MD
*Please don't confuse this for the common amino acid CARNITINE
(L-Carnitine).
Although carnosine (also known as L-carnosine) has been known
for about a century, its antiaging properties have only been
extensively studied during the past few years. A recent literature
review revealed over 780 published studies on carnosine, mainly
by Russian and Japanese researchers. However, more widespread
interest in this natural non-toxic product has only recently
been increased, fuelled by dramatic Australian and British
discoveries about its antiaging actions (1).
Carnosine (B-alanyl-L-histidine) is a naturally-occurring
di-peptide (a combination of two aminoacids), found in muscle,
brain and other innervated animal and human tissues. It is
formed by a process involving the enzyme carnosine-synthetase
which bonds the aminoacids alinine and histidine. This process
occurs mainly in muscles and brain. It is kept in equilibrium
by the carnisinases which are enzymes specifically aimed at
inactivating carnosine in the tissues or in the blood.
There are several other related dipeptides such as carcinine,
anserrine, homocarnosine and ophidine, all of which are naturally-occurring.
These are believed to be buffering agents, helping to maintain
the homeostatic equilebrium (2).
High concentrations of carnosine are present in long-lived
cells (such as in neuronal tissues). The concentration of
carnosine in muscles correlates with maximum lifespan, a fact
that makes it a promising bio-marker of aging. It is high
in actively contracting muscles and low in cases of muscular
disease such as Duchennes's muscular dystrophy. Its concentration
in mammalian muscles possibly decreases with age, a fact which
strengthens the case for supplementation.
In cases of cataract in animals, carnosine concentration in
the lens was found to be low. The lower the concentration
of carnosine, the higher the severity of cataract. Rabbits
fed on a high cholesterol diet, were found to be well protected
against atherosclerosis and cataract, if given carnosine supplements.
In another experiment, dogs were also found to be protected
against cataract if given carnosine supplements (2).
Antioxidant Properties
Carnosine is widely believed to be an antioxidant which stabilizes
and protects the cell membrane. Specifically, as a water-soluble
free radical scavenger it prevents lipid peroxidation within
the cell membrane (3). It is thought to be a natural counterpart
to lipid-soluble antioxidants such as vitamin E. Maybe it
is not a coincidence that carnosine increases vitamin E levels
in rats.
Many antioxidants are aimed at preventing free radicals (FR)
from entering the tissues, but have no effect after this first
line of defence is broken. Carnosine is not only effective
in prevention, but it is also active after FR react to form
other dangerous compounds. So, it protects the tissues from
these damaging 'second-wave' chemicals. For example, a highly
reactive lipid persoxidation end-product called malondialdegyde
(MDA)- a deliterious product of a free radical reaction- is
blocked by carnosine (4,5). MDA, if left uncontrolled, can
cause damage to lipids, enzymes and DNA, and plays a part
in the process of atherosclerosis, joint inflammation, cataract
formation and aging in general. Carnosine, by reacting and
inactivating MDA, sacrifices itself in order to protet the
aminoacids on the protein molecule.
Other Benefits:
Carnosine plays a part in neurotransmission, it is a heavy
metal binder (chelates ionic metals) and modulates enzymatic
activities. Other actions, some of which are not extensively
studies, include:
- anti-neoplastic properties, which make it a potentially
beneficial agent for use in cancer prevention.
- immune booster (it stimulates maturation of immunocompetent
cells), and reduces inflammation.
- wound healing properties and protection against radiation
damage (both preventing damage and reversing the post-radiation
syndrome). Laboratory animals treated with carnosine were
found to have faster and better wound healing rates compared
to controls. This has potential applications to treating burns,
wounds following surgery, or during nutritional preparation
for surgery (6).
- a reduction of gastric ulceration (particularly when the
ulcer is related to stress), both by preventing the formation
of the ulcer and by healing it (carnosine increases the formation
of granulation tissue). It does not affect acid secretion.
Glycosylation:
Perhaps, the most important action of carnosine is its anti-glycosylation
effect (8). One of the cardinal processes of aging, apart
from free-radical damage, is the process of glycosylation
(or glycation). During normal, everyday metabolism, sugar
aldehydes may react with the aminoacids on the protein molecule.
The result is the formation of AGEs (Advance Glycosylation
End-products). These are abnormal, cross-linked, oxidised
products which are thought to cause extensive damage to the
organism. Carnosine blocks this deleterious reaction, protecting
against cross-linking of proteins, cross-linking of proteins
to DNA molecules, and formation of other abnormal proteins,
all of which are fundamental features of the aging process.
Other anti-glycators such as aminoguanidne may also protect
against glycosylation but not as effectively as carnosine.
Some aminoacids (arginine or lysine) are also able to combine
with glucose in order to eliminate dangerous AGEs, but the
end-product of this reaction is mutagenic (i.e. it may cause
cancer). The combination of carnosine with glucose however
is not mutagenic.
Specifically, carnosine reacts with and inactivates aldehydes
and ketones, reducing protein glycosylation and the formation
of AGEs. It also binds to already formed AGEs and inactivates
them. Normally, AGEs are removed by scavenging macrophages
(immune system cells) which carry special receptors called
RAGEs. Carnosine facilitates this process of elimination,
by helping macrophages to better recognise the AGE molecule.
Because of its anti-glycosylation actions, carnosine may be
useful in treating or preventing diabetic complications such
as cataract, neuropathy and kidney failure.
Amyloid Protection:
In experiments, treatment with carnosine was found to reduce
or completely prevent cell damage caused by beta amyloid (9),
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 diseases such as dementia.
There have been some concerns regarding carnosine's ability
to form lipofuscin (the age pigment commonly found in the
aging brain and in other tissues). Lipofuscin is merely a
sign that other deleterious reactions have already taken place.
For example, free radicals and toxic aldehydes may react with
valuable proteins as described above, and cause damage, leaving
lipofuscin as a left-over product. (Ed.-It may be advisable
to take a lipofuscin supplement such as Centrophenoxine or
acetyl-L-carnitine whilst on a carnosine program). One way
to save the protein molecule is to use carnosine instead.
Carnosine actively and swiftly binds to aldehydes before these
are able to cause any damage. The end-result of this reaction
may also be inactive lipofuscin compounds.
In this case, lipofuscin is formed not by wasting valuable
protein material but by using sacrificial carnosine, leaving
the proteins free to function properly. Lipofuscin, however
formed, is thought to be generally inactive to normally everyday
situations. High amounts of free radicals and toxin in the
organism are best inactivated by using supplementary carnosine
than tissue protein. Of course, it would be best to reduce
the exposure to too many free radicals in the first place.
This can be achieved for example, by avoiding pollution, cigarette
smoking, sedentary life, and unsuitable nutrition.
Use on Humans:
After dozens of reports about carnosine's antiaging actions
in laboratory experiments, the next logical step was to start
using it on humans, specifically for antiaging purposes. Carnosine
supplements have been used in the past by body-builders, atheletes
and others, but its use has been confined mainly for improving
muscular fatigue, and not for longevity.
Recently, eye drops containing carnosine have been developed
and used by Russian researchers (10). The drops were found
to be effective in treating human corneal erosions and other
corneal diseases. For example, carnosine drops accelerate
the healing of ulcers in herpes and bacterial infections of
the eye.
During a preliminary experiment designed specifically for
antiaging (11), I used L-carnosine supplements (50 mg daily)
on 20 healthy human volunteers, aged 40 - 75 years, for a
period of 1-4 months. No side affects were reported. Five
users noticed significant improvements in their facial appearance
(firmer facial muscles), muscular stamina and general well-being.
Five others reported possible benefits, for example better
sleep patterns, improved clarity of thought and increased
libido. The rest did not report any noticeable effects. This
is not surprising because supplementation with carnosine is
not expected to show any significant noticeable benefits in
a short time, but it should be used as an insurance against
deleterious effects of the aging process. If any benefits
are noted, these should be considered as an added extra bonus.
It is worthwhile persevering with the supplementation long
term, even if you do not experience any obvious benefits,
as you will still be well protected against aging.
Carnosine can be used together with vitamin E and/or Co-enzyme
Q10 for full antioxidant protection, but even if it is used
on its own it should still confer significant protection both
against free radicals and against glycosylation. Indeed, the
carnosine preparation I used in my experiments contains also
30 iu of vitamin E as standard. Other nutritional products
such as GH (growth hormone)-releasers are fine to use with
carnosine, if required. Some people prefer to use 100 mg of
carnosine a day (i.e. double the initial standard dose) and
they find that there are still no side effects. It may be
preferable however to only start with 50 mg a day under advice
from your physician or nutritionist, and only increase the
dose if recommended so following professional advice. Foodstuffs
containing dietary carnosine are lean red meat, and chicken.
Conclusion:
Where do we go from here? Further experiments are in progress,
aimed at examining more widely the effects of carnosine on
human aging. Those who want to be at the forefront of innovative
antiaging medicine should be taking carnosine now. It is expected
that carnosine supplementation will become much more widespread
during the next five years, making carnosine as popular as
vitamin E is today.
Footnote:
Anyone interested in joining the British Longevity Society
can contact its founder,
Dr. Marios Kyriazis at:
British Longevity Society
PO Box 71, Dept I,
Northampton NN1 5HJ
England
or email: kyriazis@antiageing.freeserve.co.uk or take a look
at their website at www.antiageing.freeserve.co.uk
References
1) Hipkiss A. Carnosine, a protective,
anti-ageing peptide? Int J Biochem Cell Biol, 1998, 30; 863-868.
2) Quinn PJ, Boldyrev AA, Formaziuk VE. Carnosine: its properties,
functions and potential therapeutic applications. Mol Aspects
Med, 1992, 13(5);379-444.
3) Tamba M, et al. Hydroxyl radical scavenging by carnosine
and Cu(ii)-carnosine complexes. Int J Radiat Biol, 1999 75(9);1177-1188.
4) Hipkiss A, et al. Protective effects of carnosine against
MDA-induced toxicity towards cultured rat brain endothelial
cells. Neuroscience Letters, 1997, 135-138.
5) Hipkiss A et al. Protective effects of carnosine against
protein modification mediated by malondialdehyde and hypochlorite.
Bioch Biophys Acta 1998, 1380;46-54.
6) Roberts PR, Black KW, Santamauro JT. Dietary peptides improve
wound healing following surgery. Nutrition, 1998, 14(3);266-269.
7) McFarland GA, Holliday R. Further evidence for the rejuvenating
effects of the dipetide L-carnosine on cultured human diploid
fibroblast. Exp Gerontol 1999 34(1);35-45.
8) Hipkiss A, Chana H. Carnosine protects proteins against
methylglyoxal-mediated modicatiations. Biochem Biophys Res
Comm 1998, 248 (1); 28-32.
9) Preston J et al. Toxic effects of B-amyloid on immortalised
rat brain endothelial cell: protection by carnosine, homocarnosine
and B-alanine. Neuroscience letters 1998, 242; 105-108.
10) Maichuk IuF, Formaziuk VE, Sergienko VI. Development of
carnosine eye drops and assessing their efficiency in corneal
diseases. Vestn Oftalmol 1997,113(6);27-31. 11) Kyriazis M,
1999, Data on file.
DISCLAIMER: ALL INFORMATION IS EDUCATIONAL AND PROVIDED UNDER
IAS TERMS AND CONDITIONS. IT DOES NOT, AND SHOULD NOT, REPLACE
THE ADVICE OF YOUR PHYSICIAN.
Last Updated: Wednesday, March 21, 2001
© 2002 International Antiaging systems
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