Carnosine: the new anti-aging supplement
by Marios Kyriazis MD
Through 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 nontoxic product has only recently been
increased, fuelled by dramatic Australian and British discoveries
about its antiaging actions (1). to order
Carnosine (B-alanyl-L-histidine) is a naturally-occurring di-peptide
(a combination of two amino acids), 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
amino acids 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 equilibrium (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 he 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 from
entering the tissues, but have no effect after this first line of
defense is broken. Carnosine is not only effective in prevention,
but it is also active after f ree radicals react to form other
dangerous compounds. So, it protects the tissues from these
damaging 'second-wave' chemicals. For example, a highly reactive
lipid peroxidation end-product called malondialdegyde (MDA)- a
deleterious 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 protect the amino acids 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 studied 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
(5).
* 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 mino acids on the protein
molecule. The result is the formation of AGEs (Advance
Glycosylation End-products). These are abnormal, cross-linked.
oxidized 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 aminoguanidine may also protect
against glycosylation hut not as effectively as carnosine. Some
amino acids (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 recognize 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 DMAE or acetyl-L-carnitine while 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,
athletes 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 (II), I used L-carnosine supplements (50 rng 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 (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 he preferable
however to only start with 50 mg a day under advice from your
physician or nutritionist, and only increase the dose if
recommended following professional advice. Foodstuffs containing
dietary carnosineare 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 he at the forefront of
innovative antiaging medicine should he 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.
References
1) Ilipkiss A. Carnosine. a protective, anti-ageing peptide? Int J
Biochem Cell Biol. 1998, 30: S63-868.
2) Quinn PL Boldyrev AA. Formaziuk VH. Carnosine: its properties,
functions and potential therapeutic applications. Mol Aspects Mod,
1992, 13(5):379-444.
3) Tarnha M, et al. Hydroxyl radical scavenging by carnosine and
Cu(ii)-carm)sine complexes. Int J Radial Biol, 1999 75(9):1
177-1188.
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) Ilipkiss A et al. Protective effects of carnosine against
protein modification mediated by nialondialdchyde 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):26h-2^9.
7) McFarlandGA,HollidayR. Further evidence for the rejuvenating
effects of the dipeptide I .-carnosine on cultured human diploid
fibroblast. Exp Gerontol 1999 34(l):35-45.
8) Ilipkiss A, Ghana 14. Carnosine protects proteins against
rnelhyiglyoxal-mediated modicatiations. Biochem Biophys Rcs Goinm
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 luF, Formaziuk VF. Sergienku VI. Development of
carnosine eye drops and assessing their efficiency in corneal
diseases. Vestn Oftalmol 1997.1 13(ft);27-31.
11 ) Kynazis M. 1999. Data on file.
*Statements
contained herein have not been evaluated by the
Food and Drug Administration. These products are
not intended to diagnose, treat and cure or
prevent disease. Always consult with your
professional health care provider before
changing any medication.**
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