Is N-acetylcarnosine
the cure for cataract?
By Robert Mason Ph.D. and Phil Micans PharmB.
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Cataract is the leading cause of blindness
and accounts for about 42% of all such cases worldwide, and this
is in-spite of the availability of effective surgical treatment.
Today we have the appalling situation where more than 17 million
people around the world are blind because of cataract and 28,000
new cases are reported everyday. In developing countries, there
is simply not a sufficient number of surgeons to perform cataract
operations.
Cataract surgery is the most commonly performed surgical procedure
in people over 65-years of age, and 43% of all visits to ophthalmologists
by Medicare patients in the US are directly associated with cataract.
Meanwhile, approximately 25% of the population
over 65, (and about 50% over 80) have a serious loss of vision
due to cataract. Since this is the population that is most susceptible
to lens opacification and as this section of the population is
expected to increase dramatically, the numbers of individuals
with cataract is set to explode!
For example, the World Health Organization anticipates that within
the next 25-years, that 20% of the population will be 65 or older.
Furthermore, the single largest growing section of the population
are those over 85 and their actual numbers are expected to quadruple
in about the same period. Such a rapidly burgeoning older population
can only increase the numbers of individuals suffering from cataract.
Of course, there is also the economic impact.
Currently 1.35 million cataract operations are performed annually
in the United States alone and Medicare estimates the annual cost
at $3.5 billion! There's no doubt about it, cataract is a major
disease.
It is also becoming apparent that it will not be possible to eliminate
the overall problems (including blindness), caused by cataract
with the current procedures. With so many people presenting the
afflictions of maturity onset cataract, it appears not to be possible
to train in-time, the necessary numbers of surgeons required.
In-fact, as-it-stands, it looks likely that the total number of
people with serious eye-disorders because of cataract, will increase
dramatically worldwide.
Surgical complications:
There is another aspect to the problem that is rarely discussed.
While cataract surgery is generally recognised as being one of
the safest operations, there is a significant complication rate.
For example, in the United States 30% to 50% of all patients having
cataract extraction, develop opacification of the posterior lens
capsule within two years and require further lazer treatment.
Since the number of cataract operations
is so large, even a small percentage of complications represents
a significant number of people. Of the patients having cataract
surgery, 0.8% have retinal detachments, 0.6% to 1.3% are hospitalized
for corneal edema (or require corneal transplantation), and 0.1%
present endophthalmitis.
Thus, aside from secondary cataract, about 2% of the 1.35 million
(or approximately 27,000 individuals), just in the US each year,
develop serious complications as a result of cataract surgery.
It is therefore difficult to support the
argument that cataract research is unimportant with statistics
such as those cited above. The large and growing number of people
blind with cataract and the significant complication rate, should
be sufficient reason to increase cataract research.
The considerable discomfort experienced
by patients as their vision diminishes, and the complete loss
of accommodation resulting in the removal of the lens should also
be recognised. Besides the possible complications, an artificial
lens just does not have the overall optical qualities of a natural
lens.
A medical solution is required that will
maintain the transparency of the lens. Even if the development
of cataract can be delayed by 10-years, the overall benefits would
be highly significant.
The development of N-acetylcarnosine:
Russian researchers and scientists and over the last several-years
have developed and tested a unique new form of the di-peptide,
carnosine. This form of carnosine is known as n-acetylcarnosine
and it appears to be the first major leap forward in the treatment
and possible prevention of senile cataract.
Since having developed a proprietary method
of producing extremely high purity N-acetylcarnosine, (that has
proven itself to be a suitable ophthalmic drug for the non-surgical
treatment of age-related cataracts), N-acetylcarnosine also displays
high efficacy and physiological tolerance.
N-acetylcarnosine has a highly statistical
and very significant clinical success rate for patients within
3-6 months of treatment. Not surprisingly, many worldwide patents,
including its use for senile cataract, have already been issued.
It is also interesting to note that N-acetylcarnosine eye-drops
are patented for use in open-angle glaucoma, but as yet, the research
for that disorder remains unpublished.
Human trials:
Carnosine eye-drops were used in a clinical trial to treat 96
patients aged 60 and above. All the patients had senile cataract
in various degrees of maturity. The duration of the disease in
these patients ranged between 2 and 21 years.
Firstly, the researchers stopped the patient's use of all other
anti-cataract drugs. Then the patients instilled 1 or 2 drops
into each eye 3 or 4 times a day, for a period of 3 to 6 months.
The level of eyesight improvement and the
change of lens transparency was considered as an evaluation index.
The results showed that there was a pronounced effect on primary
senile cataract, the effective rate was 100% (i.e. all patients
experienced an improvement). For the more mature senile cataract
(i.e. those who had had the cataract the longest time, in some
cases more than 20-years), the effective rate was still an extremely
impressive 80%.
These are remarkable results considering that the best that could
normally be expected would be a slight improvement, a halt to
the progression and under normal (i.e. non-treated) circumstances,
a continual worsening of the disease. Importantly, it was also
noted that there were no side effects noted in any of the cases.
Another Russian study was designed to document
and quantify the changes in lens clarity over a 6 to 24 month
period for 49 volunteers. Their average age was 65 and all suffered
from senile cataract of a minimal to advanced opacification.
The patients received either a 1% solution
of N-acetylcarnosine eye-drops or a placebo, (as 2-drops twice
a day into each eye). The patients were then evaluated at 2 and
6 month periods. The tests consisted of ophthalmoscopy (glare
test), stereocinematagraphic (slit-image) and retro-illumination
(photography). A computerized digital analysis then displayed
the light scattering and absorbing effects of the centers of each
lens.
At 6-months, 88.9% of all eyes treated
with N-acetylcarnosine had an improvement of glare sensitivity
(lowest individual score was a 27% improvement, right the way
up to a 100% improvement). 41.5% of all eyes treated with N-acetylcarnosine
had a significant improvement of the transmissivity of the lens,
but perhaps most importantly 90% of the eyes treated with N-acetylcarnosine
showed an improvement in visual acuity. Meanwhile, in the placebo
group there was little change in eye quality at 6-months and a
gradual deterioration at 12 to 24 months.
Importantly, this study also showed that
at 24-months the N-acetylcarnosine treated group, (who already
had significant improvement to the quality of their eyesight),
sustained these results with continued use of the N-acetylcarnosine
eye-drops.
Once again, no significant side effects were noted in any cases
throughout the 2-year period.
Another interesting study also evaluated
patients between the ages of 48 and 60, who had various degrees
of eyesight impairment, but who did not have the symptoms of cataract.
After a course of treatment ranging from 2 to 6 months the conclusion
was, that the eye-drops alleviated eye-tiredness and continued
to improve eyesight (i.e. there was more clear vision). The subjects
reported that the treatment "brightened" and "relaxed"
their eyes. This is an important indicator that the eye-drops
have a value both for preventative purposes, as well as medical
applications.
At this time, it is now believed that carnosine
eye-drop treatment has been applied to over one thousand patients
with senile cataract in China and Russia, (those countries are
home to the principal researchers behind the work). Clear evidence
is emerging that N-acetylcarnosine eye-drops are a safe, effective
treatment and potential preventative against senile cataract.
N-acetylcarnosine's method of action:
Cataract is primarily a glycosylation problem. This reaction occurs
when proteins became cross-linked (and hence impaired). The result
of this reaction leads to the discoloration of the eye-lens to
yellow and brown, and hence the impairment of vision.
As carnosine is known to compete on the molecule for the glycating
agent and protect cellular structures against aldehydes, carnosine
can therefore slow and help to prevent proteins from becoming
cross-linked, (and in this case from becoming cataract).
N-acetylcarnosine has been shown to be highly resistant to carnosinase,
(the natural enzyme that breaks down L-carnosine into histamine
etc.). An experiment on rabbits showed that N-acetylcarnosine
eye drops allow themselves to be broken down into L-carnosine
once inside the eye's aqueous humor, (a process that occurs within
15 to 30 minutes after application of the eye-drops).
L-carnosine is a potent anti-oxidant and
is particularly effective against "extreme" free-radicals,
such as the Superoxide and the Hydroxyl. It is therefore presumed,
that the anti-oxidant role of L-carnosine (within the aqueous
humor), is a major factor in slowing and preventing the appearance
of cataract.
However, when L-carnosine eye-drops were
used there was no presence of L-carnosine in the aqueous humor,
(even after 30-minutes). This may be because L-carnosine is broken
down early into histamine etc., before it reaches the aqueous
humor. N-acetylcarnosine may act as a "carrier" for
L-carnosine delivering it to where it is needed. So the powerful
anti-oxidant abilities of carnosine within the eye, and the prevention
of cross-linking, helps to explain why N-acetylcarnosine is effective
at preventing and slowing cataract, perhaps even halting it. But
it doesn't explain why N-acetylcarnosine has been shown to reverse
cataract. But we may already know the answer.
For example, it is known that when carnosine is delivered in high
doses, that it can reverse protein-aldehyde cross-linking, (this
reaction is normally very difficult to reverse). Under these circumstances,
carnosine has been shown to have a "rejuvenating" effect
on cultured cells.
Cataract develops when anti-oxidant defenses
are exhausted, leading to the cross-linking of the lens crystallins,
(producing a clouded lens, and hence impaired eyesight). We can
assume that the regular use of a 1% N-acetylcarnosine eye-drop
(as used in the clinical trials), delivers "a high-dose of
carnosine capable of reversing the lens cross-linking," and
hence the reduction and eradication of cataract.
So in conclusion, N-acetylcarnosine eye-drops
appear to act as a universal anti-oxidant, both in the lipid phase
of the cellular lens membranes and in the aqueous environment.
N-acetylcarnosine eye-drops reduce and protect the crystalline
lens from oxidative stress-induced, cross-linking damage.
N-acetylcarnosine compared to L-carnosine:
We may logically ask the question; why have N-acetylcarnosine
eye-drops been shown to have this action upon cataract, and yet
L-carnosine (which is its sister di-peptide) appears to have little
benefit? Mark Babizhayev Ph.D., one of the principal Russian researchers
behind the clinical trials with N-acetylcarnosine eye-drops gave
us this reply to that very same question:
"I believe that the application of L-carnosine for the treatment
of human cataracts is misleading. This is because L-carnosine
readily becomes a substrate for the activity of natural peptidases
(i.e. carnosinase) in the aqueous humor. So much so, that there
is no sign of L-carnosine in the aqueous humor within 15 minutes
after instillation. Furthermore, I consider that L-carnosine eye-drops
may even be harmful for eyes because it gradually releases histamine,
which, located as it would be in the presence of the eye-lens
is a very toxic agent. However, N-acetylcarnosine eye-drops are
resistant to hydrolysis with natural carnosinase. Therefore, N-acetylcarnosine
is the only currently known agent which reverses and prevents
human cataracts."
The scientists, Dr. Hipkiss and Dr. Kyriazis
have concluded that some of the benefits of oral L-carnosine probably
derive after carnosinase breaks down into histamine. However,
it would appear that in the case of eye-drops, L-carnosine must
be avoided.
Conclusion:
Cataract is a widespread age-related affliction and N-acetylcarnosine
eye-drops appear to be a highly efficacious and safe treatment
for cataract. As such, I suspect that this supplement is going
to become one of the most important new discoveries, and will
have a major impact on the way that cataract is controlled.
DISCLAIMER;
ALL INFORMATION IS EDUCATIONAL AND
PROVIDED UNDER IAS TERMS AND CONDITIONS.
IT DOES NOT AND SHOULD NOT REPLACE THE ADVICE OF YOUR PHYSICIAN.
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Article References:
1. Boldyrev AA, Dupin AM, Bunin Aya, Babizhayev MA, Severin
SE "The antioxidative properties of carnosine, a natural
histidine containing di-peptide." Biochem. Inrern.,
1987, 15/6, 1105-1113.
2. Babizhayev MA et al "N-Acetylcarnosine, a natural
histidine-containing di-peptide, as a potent ophthalmic
drug in treatment of human cataracts." Peptides (USA)
2001, 22(6): 979-994.
3. Babizhayev MA, Yermakova
VN, Deyev Al, Seguin M-C "Imidazole-containing peptiomimetic
N-ACETYLCARNOSINEA as a potent drug for the medicinal treatment
of age-related cataract in humans." J. Anti-Aging Medicine
2000, 2, 43-62.
4. Babizhayev MA, Yermakova
VN, Semiletov yu A, Deyev Al "The natural histidine-containing
di-peptide N-acetylcarnosine as an antioxidant for ophthalmic
use." Biochemistry (Moscow), 2000, 65, 588-598.
5. Babizhayev MA, Yermakova
VN, Sakina NL, Evstigneeva RP, Rozhkova EA, Zheltukhina
GA "N-Acetycarnosine is a prodrug of L-carnosine in
ophthalmic application as antioxidant." Clin. Chim.
Acta., 1996, 254, 1-21.
6. Babizhayev MA, Bozzo
Costa E "Composizioni farmaceutiche contenenti N-acetilcarnosina
per il trattamento della cataratta." A61K gruppo 37/00
cap 20122 MI 15.10.1993. Italian patent.
7. Babizhayev MA, Bozzo
Costa E "Pharmaceutical compositions containing N-Acetylcarnosine
for the treatment of cataract." European Patent PCT/EP
94/03340 10.10.1994 Ref. SCB 238 PCT.
8. Babizhayev MA, Seguin
M-C, Gueyene J, Evstigneeva RP, Ageyeva EA, Zheltukhina
GA "L-carnosine and carcinine act as natural antioxidants
with hydroxyl-radical-scavenging and lipid peroxidase activities."
Biochem J. 304, 509-516.
9. Babizhayev MA, "Antioxidant
activity of L-carnosine, a natural histidine-containing
di-peptide in crystalline lens." Biochem. Biophys.
Acta., 1989, 1004, 363-371.
10. Babizhayev MA, Deyev
Al "Lens opacity induced by lipid peroxidation products
as a model of cataract associated with retinal disease."
Biochim. Biophys. Acta., 1989, 1004, 124-133.
11. Babizhayev MA, Deyev
Al "Free radical oxidation of lipid and thiol groups
in genesis of cataract." Biophysics (biofizika), 1986,
31, 119-125, Pergamon Journals Ltd.
12. Kantha S, Wada S, Tanaka
H, Takeushi M, Watabe S, Ochi H (1966), Biochem. Biophys.
Res. Commun. 223, 278-292.
13. Babizhayev MA, Deyev
Al, Linberg LF "Lipid peroxidation as a possible cause
of cataract." Mech. Ageing Dev. 1988, 44, 69-89.
14. Boldyrev AA, "Problems
and perspectives in studying the biological role of carnosine"
International Center for Biotechnology, Department of Biochemistry,
Lomonosov, Moscow State University.
15. Hipkiss A, (1998) Int.
J. Biochem. Mol. Biol., 30, 863-868.
16. Boldyrev AA, Dupin A,
Bunin A, Babizhayev MA, Severin SE (1987), Biochem. Int.,
15, 1107-1113.
17. Wang AM, Ma C, Xie H,
F Shen "Medical application of carnosine" Department
of Biochemistry and Neurobiology, Harbin Medical University,
China.
18. Kyriazis M, "Low
dose carnosine is effective" International Anti-Aging
Systems, Anti-Aging Bulletin, Winter 2001, Volume 4, Issue
11, 18-24.
19. Kyriazis M, "Carnosine,
the new anti-aging supplement" International Anti-Aging
Systems, Anti-Aging Bulletin, Summer 2000, Volume 4, Issue
6, 3-7.
20. World Health Organisation,
Ageing and Health, Website: http://www.who.int/ageing/scope.html
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